Surfing the NASH Tsunami: Recent Episodes
HEP Dynamics LLC
Driving the Discussion in Fatty Liver Disease. Join hepatology researcher and Key Opinion Leader Stephen Harrison, Liver Wellness Advocate Louise Campbell, and Forecasting and Pricing Guru Roger Green as they discuss the issues affecting the evolving NASH market from their own unique perspectives on the Surfing the NASH Tsunami podcast. #NASH #NAFLD #FattyLiver
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The original roundtable has three segments. Surfing the MASH Tsunami is preempting the third segment, which will be posted next week, to share our co-hosts' reactions to the positivity and energy they felt from a group of empowered SLD advocates.
Immediately after the roundtable, Louise suggested to Roger that they record a separate conversation sharing their reactions to what they had just witnessed. They turned the recording equipment on and resumed their conversation.
Roger starts by noting that this is the first SurfingMASH episode comprised entirely of patient advocates at a moment when advocates felt empowered and optimistic. (Also, the Fellows were the first advocates to appear on SurfingMASH who are not part of the Advocate KOL community.)
For Louise, her overpowering reaction is to the passion, because passion breeds energy and empowerment. She notes that the SLD advocates came from an array of liver-related backgrounds and from HIV, the original sources of truly empowered patients some 30 years ago.
Roger shares two thoughts. As he listened to the roundtable, he recalled earlier episodes, some four to five years ago, when it seemed that the physician KOL community was not in sync with the patient advocates' goals and needs. Continuing along this train of thought, he discusses the shift in identity from “MASH patient” to “person living with MASH.” To Roger, the term "MASH patient" suggests a person defined by the disease, whereas the term "patient living with MASH" empowers individual patients to manage the disease and its place in their lives in whatever way they choose. The advocates, he says, choose to learn and speak out confidently.
During the roundtable, Elena mentioned Úna Keightly, a Harrison Fellow from Ireland, who spoke from the floor at Paris MASH to request that patients learn about the outcomes of the trials in which they participate, whether the outcome is deemed a success or a failure. For the "MASH patient," a failed trial feels like a personal failure, but for a "person living the MASH," even the failed trial becomes an opportunity to learn about the disease and contribute to a long-term solution.
Louise mentions a comment from Harrison Fellow Pam Miller about her cardiologist giving her a potentially hepatotoxic medication without considering Pam's liver status. This reminded both Louise and Roger of a comment former Global Liver Institute President Donna Cryer made years ago to the effect of "it doesn't matter what kills me. If I'm dead, I'm dead."
From here, the conversation shifts to other changes in disease description Louise and Roger foresee:
- Describing the disease itself in more accessible terms, such as "liver stiffness" vs. "fibrosis level."
- Increasing the groups of attendees at events to include not only patients, but also the APPs who will provide much of the actual patient-level care.
- Educating those who still mischaracterize MASLD as “a bit of fat” that requires no action.
- Focusing more attention on post-menopausal women, who Louise notes are most likely to exhibit advanced SLD and cirrhosis.
- Being more sensitive to issues that drive changes in patients' quality of life, which might be the impact of hepatic encephalopathy, but might also relate to lean mass wasting with incretin agonists.
Both foresee a growing “army” of advocates that can drive earlier detection, smarter trial design, and better everyday care. They cite some specific examples from the Fellows in the roundtable and others from their own life experiences.
Ultimately, Louise and Roger share their belief that this program is an excellent tribute to Stephen Harrison, who strongly believed in the importance of patient advocates and the messages they convey.
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In June, the Fatty Liver Foundation officially launched the Stephen A. Harrison Patient Advocacy program and announced its first class of 20 Fellows. In today's conversation, the program's organizers, Fatty Liver Foundation President Wayne Eskridge and Program Co-ordinator Elena Samsonova, share the program's goals and objectives with Louise Campbell and Roger Green.
The bulk of this conversation focuses on the program's goals and scope for its first year. First, though, Harrison Fellow Julie Peyout from Canada describes what it means to her to be part of the program. (Julie's connection was interrupted while her colleagues were answering this question earlier in the roundtable.)
Wayne points out that, while the FLF originally focused on NAFLD and NASH, the new nomenclature has led them to broaden their focus to all forms of SLD. (He plans to rebrand as the Steatotic Liver Foundation.)
Elena describes the program's four "pillars":
- Mentorship - Having an experienced advocate guide each Fellow as they pursue the next steps in their advocacy.
- Education - Learning more about SLD.
- Networking - Connecting with other advocates and industry decision-makers at conferences.
- Fellowship - Supporting each other as they grow new skills and have new experiences.
Wayne elaborates on some of the "robust flow of information" the Fellows will receive. He focuses on three areas: what he calls "the nuts and bolts of the regulatory process", clinical trials from the researcher and trialist perspectives and more general information about how different functions inside a pharmaceutical company work.
As the conversation winds down, Roger cites this podcast's mission to "make a big fat dent in MASH" and asks the Fellows about the dent they anticipate making. Elena responds with a story from the previous week's meetings, during which another Fellow stated that when she has participated in trials, she has never received information on what the trial results and learnings actually showed. Elena describes watching clinicians and trialists respond by discussing ways participants could receive such information in the future.
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In June, the Fatty Liver Foundation officially launched the Stephen A. Harrison Patient Advocacy program and announced its first class of 20 Fellows. In today's conversation, Louise Campbell and Roger Green interview the founders to learn what motivated them to launch this program, and we meet five of the initial Fellows.
Program Co-ordinator Elena Samsonova opens the conversation by celebrating last week's onboarding of 20 inaugural Fellows and the chemistry between them. She goes on to introduce five of them:
- Steven Rodrigues (ALD, UK citizen) shares his recent experience giving a 15-minute national interview on BBC Radio 5 discussing ALD clinical insights.
- Silvana Lesidrenska (Hepatitis B, Bulgaria) shares her desire to learn more about SLD as part of her advocacy leading a liver patients association in Bulgaria.
- Julie Peyout (MASH, Canada) is a great-grandmother who was recently found free after therapy for Non-Hodgkin's Lymphoma.
- Pam Miller (MASH cirrhosis, US) learned 24 years ago that she had MASH cirrhosis when her surgeon aborted a bariatric procedure. Since then, she has lived with cirrhosis and experienced hepatic encephalopathy (HE). She has participated in clinical trials, lobbied legislators, and collaborated with professional societies.
- Melanie Smith (MASH cirrhosis, US) has lived with stage-4 MASH cirrhosis since age 36 (sixteen years ago) and experiences hepatic encephalopathy (HE). She has led support groups for over a decade.
Next, Fatty Liver Foundation President Wayne Eskridge recounts the program's foundational story. He describes Stephen as a man with a genuine commitment to patients and his passing as a "tremendous loss." This led Wayne to discuss this idea with Rebecca Taub of Madrigal, "another one of my heroes." (Madrigal supports this program.)
Elena describes how she joined the FLF to lead this program. Roger asks the Fellows where and how they intend to make a difference. Their goals vary, from working in a Biopharma company advocating for patients to "going to the top," perhaps even lobbying the HHS Secretary, to expanding their own education and knowledge about the various forms of SLD.
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00:00:00 - Surf's Up: Season 6 Episode 14
Louise Campbell and Roger Green interview key players in the inaugural Dr. Stephen A. Harrison Patient Advocacy Fellowship program, including Wayne Eskridge of the Fatty Liver Foundation (FLF), which initiated the program, Program Coordinator Elena Samsonova, and five Harrison Fellows.
00:05:08 - Part I: How the Harrison Fellowship Came To Be
Elena opens by celebrating last week's onboarding of 20 inaugural Fellows and the chemistry between them. She goes on to introduce five of them:
- Steven Rodrigues (ALD, UK citizen) shares his recent experience giving a 15-minute national interview on BBC Radio 5 discussing ALD clinical insights.
- Silvana Lesidrenska (Hepatitis B, Bulgaria) shares her desire to learn more about SLD as part of her advocacy leading a liver patients association in Bulgaria.
- Julie Peyout (MASH, Canada) is a great-grandmother who was recently found free after therapy for Non-Hodgkin's Lymphoma.
- Pam Miller (MASH cirrhosis, US) learned 24 years ago that she had MASH cirrhosis when her surgeon aborted a bariatric procedure. Since then, she has lived with cirrhosis and experienced hepatic encephalopathy (HE). She has participated in clinical trials, lobbied legislators, and collaborated with professional societies.
- Melanie Smith (MASH cirrhosis, US) has lived with stage-4 MASH cirrhosis since age 36 (sixteen years ago) and experiences hepatic encephalopathy (HE). She has led support groups for over a decade.
Next, Wayne recounts the program's foundational story. He describes Stephen as a man with a genuine commitment to patients and his passing as a "tremendous loss." This led Wayne to discuss this idea with Rebecca Taub of Madrigal, "another one of my heroes." (Madrigal supports this program.)
Elena describes how she joined the FLF to lead this program. Roger asks the Fellows where and how they intend to make a difference. Their goals vary, from working in a Biopharma company advocating for patients to "going to the top," perhaps even lobbying the HHS Secretary, to expanding their own education and knowledge about the various forms of SLD.
00:34:46 - Part II: Goals of the Harrison Fellowship Program
This conversation focuses on the program's goals and scope for its first year. Wayne points out that, while the FLF originally focused on NAFLD and NASH, the new nomenclature has led them to broaden their focus to all forms of SLD. (He plans to rebrand as the Steatotic Liver Foundation.)
Elena, it describes the program's four "pillars":
- Mentorship - Having an experienced advocate guide each Fellow as they pursue the next steps as Advocates.
- Education - Learning more about SLD.
- Networking - Connecting with other advocates and industry decision-makers at conferences.
- Fellowship - Supporting each other as they grow new skills and have new experiences.
00:55:09 - Experts: Louise and Roger Discuss This Roundtable
Roger and Louise share their enthusiasm for the unprecedented sense of empowerment they felt among patient advocates while leading this discussion. Both comment on the identity shift from “MASH patient” to “person living with MASH.” Louise mentions that doctors or APPs still minimize disease by characterizing MASLD as “a bit of fat” that requires no action. Roger suggests that focusing on the total patient will include not only the efficacy of medicines but also potential side effects or safety concerns. Louise comments that advanced disease and cirrhosis occur most often in post-menopausal women with cirrhosis, and discusses implications. Both foresee a growing “army” of advocates that can drive earlier detection, smarter trial design, and better everyday care.
01:11:11 - Business Report
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This discussion on ways to improve MASH patient management comes from the early July roundtable on "Major Issues of the First Six Months of 2025." As a reminder, that roundtable included the three co-hosts (Louise, Jörn Schattenberg and Roger Green)
Roger drives this conversation, focusing on two very different, yet very important issues: the first is the increasing dynamism of the in-office scanning market, with leader Echosens developing new products and services, while companies like e-Scopics, Sonic Incytes, and Mindray (Hepatus) are introducing new devices with competing profiles. Roger discusses the idea that some scanners keep all data resident in the machine, while others send it immediately to the cloud. Louise suggests that while we should welcome any reliable scanning device to the market, Echosens has a significant advantage in terms of data richness and depth when compared to all competitors. (NOTE: This benefit became clearer when Echosens submitted a Letter of Intent to the FDA to qualify liver stiffness measurement (LSM) using VCTE, as found in FibroScan, as a reasonably likely surrogate endpoint in clinical trials for MASH.
Separately, he lists some concerns about how the Trump Administration's focus on cutting services to the poor, coupled with Robert F. Kennedy Jr.'s distrust of pharmaceuticals and mainstream health research, might limit the number of Americans with access to healthcare and the kinds of care they can access.
At the end of this conversation, Roger asks Jörn and Louise what they consider major issues for the next six months.
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Last month, The Lancet posted online an article from Stine Johansen, Fredrik Åberg, Emmanuel Tsochatzis and Aleksander Krag, titled "Screening for Advanced Liver Disease." The article aims to update the Wilson and Jungner criteria, initially developed in 1960, to address modern needs and issues. In this conversation, Professor Krag and Dr. Johansen join Roger Green to discuss their article.
There are many nuances and high points to cover in this thoughtful, fairly lengthy conversation, but one key point is that screening a mass population for HCC or cirrhosis has an entirely different set of issues and criteria compared to the screening usually discussed on this podcast, which involves identifying a population at increased risk for MASLD or MASH and screening them. Also, healthcare is far more expensive than it was in 1960 with a plethora of high-cost ways to diagnose, treat and manage patients.
As a result, the authors started with the 10 Wilson and Jungner criteria and added eight more. During this conversation, Stine emphasizes the need for a comprehensive clinical trial on this issue, and all panelists agree that LiverAIM is likely to serve as the study.
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This discussion on ways to improve MASH patient management comes from the early July roundtable on "Major Issues of the First Six Months of 2025." As a reminder, that roundtable included the three co-hosts (Louise, Jörn Schattenberg and Roger Green)
Louise drives this conversation based on two related issues she sees emerging: (i) increasing opportunities for motivated patients to manage their own health and (ii) managing the total patient in an environment where people may be taking incretin agonists as if they are consumer drugs. With increased access to scanning, providers can monitor patients (and patients can self-monitor) more closely. However, some of the issues a provider might find are tricky: patients who undertake what Louise describes as "the sneaky areas patients think are normal, but are probably contributing to disease" due to miseducation or no education on healthy eating and lifestyle, or patients purchasing and using incretin agonists through consumer channels, but possibly at subtherapeutic doses. Vigilance and probing are key here, but health systems will need to train more people on the types of probing that uncover underlying issues and behaviors that patients mistakenly believe to be healthy.
The discussion also extends to the role of NITs in diagnosis and patient management, and how providers need to shift the paradigm away from describing a patient by fibrosis stage and instead focus on the amount of fat in the liver and its overall suppleness.
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00:00:00 - Surf's Up: Season 6 Episode 13
Louise Campbell, Jörn Schattenberg and Roger Green continue their discussion of some major issues from earlier this year, while co-authors Aleksander Krag and Stine Johanset join Roger to discuss their recent publication in The Lancet, titled "Screening for Advanced Liver Disease."
00:04:45 - Major Issues of the First Six Months: Integrated Patient Management
Louise drives this conversation based on two related issues she sees emerging: (i) increasing opportunities for motivated patients to manage their own health and (ii) managing the total patient in an environment where people may be taking incretin agonists as if they are consumer drugs. With increased access to scanning, providers can monitor patients (and patients can self-monitor) more closely. However, some of the issues a provider might find are tricky: patients who undertake what Louise describes as "the sneaky areas patients think are normal, but are probably contributing to disease" due to miseducation or no education on healthy eating and lifestyle, or patients purchasing and using incretin agonists through consumer channels, but possibly at subtherapeutic doses. Vigilance and probing are key here, but health systems will need to train more people on the types of probing that uncover underlying issues and behaviors that patients mistakenly believe to be healthy.
00:21:02 - Newsmakers: Aleksander Krag and Stine Johansen discuss Screening for Advanced Liver Disease
Last month, The Lancet posted online an article from Stine Johansen, Fredrik Åberg, Emmanuel Tsochatzis and Aleksander Krag, titled "Screening for Advanced Liver Disease." The article aims to update the Wilson and Jungner criteria, originally developed in 1960, to address modern needs and issues. In this conversation, Professor Krag and Dr. Johansen join Roger Green to discuss their article.
There are many nuances and high points to cover in this thoughtful, fairly lengthy conversation, but the key point is that screening a mass population for HCC or cirrhosis has an entirely different set of issues and criteria compared to the screening usually discussed on this podcast, which involves identifying a population at increased risk for MASLD or MASH and screening them.
00:54:42 - Major Issues of the First Six Months: Changes in US Health Policy and Potential for Dynamism in the In-Office Scanning Market
Roger drives this conversation, focusing on two very different, yet very important issues: the first is the increasing dynamism of the in-office scanning market, with leader Echosens developing new products and services, while companies like e-Scopics, Sonic Incytes, and Mindray (Hepatus) are introducing new devices with competing profiles. Roger discusses the idea that some scanners keep all data resident in the machine, while others send it immediately to the cloud. Louise suggests that we should welcome any reliable scanning device to the market.
Separately, he lists some concerns about how the Trump Administration's focus on cutting services to the poor, coupled with Robert F. Kennedy Jr.'s distrust of pharmaceuticals and mainstream health research, might limit the number of Americans with access to healthcare and the kinds of care they can access.
At the end of this conversation, Roger asks Jörn and Louise what they consider major issues for the next six months.
01:11:40 - Business Report and Wrap-Up
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Key Opinion Leaders Manal Abdelmalek, Naim Alkhouri, Scott Isaacs and Zobair Younossi join Roger Green to discuss the FDA's approval of semaglutide for patients with non-cirrhotic MASH. This conversation centers on the roles that new technologies and an expanded APP population will play in MASLD and MASH management in the US, and concludes by exploring how care might look different 12 months from now, and then in subsequent years.
As panelists identify some of the changes they foresee if we are to manage the tsunami of undiagnosed MASLD patients, many comments touch on themes discussed earlier in this episode. A couple are unique. Zobair and Scott discuss the increased role that artificial intelligence and big data analytics will play in identifying high-risk patients and improving clinical pathways. Additionally, Zobair notes that we must remember that the vast majority of MASLD patients will never develop MASH. Manal foresees a more sophisticated approach to selecting pharmacotherapies as prescribers have a broader set of options, each with its own benefits and drawbacks. Scott anticipates a "paradigm shift" in which endocrinologists view MASH similarly to how they view retinopathy, neuropathy and retinopathy. Naim suggests that one year will not look tremendously different from today, but that five years from now will be an entirely different picture, which he describes in some detail.
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Key Opinion Leaders Manal Abdelmalek, Naim Alkhouri, Scott Isaacs and Zobair Younossi join Roger Green to discuss the FDA's approval of semaglutide for patients with non-cirrhotic MASH. This conversation focuses on how the US healthcare system must adapt to handle the growing number of MASH and MASLD patients who might seek treatment, given likely increases in publicity and education.
The conversation starts with a focus on the implications of semaglutide approval for hepatologists. Naim states that many hepatologists are currently uncomfortable managing patients on GLP-1 agonists. This will need to change. Manal points out that providers must check for cirrhosis when testing for MASH and understand how to respond accordingly. An increase in the number of providers having access to in-office scanning devices will facilitate this process.
Zobair shifts to a larger point: even if all related specialists integrate MASH into their practices, the actual patient care demand will require alternative pathways in which the responsibility for patient care will rest with specialist APPs. The number of APPs necessary to handle this load and trained to do so does not currently exist in the US. Increased APP training must, and will, become an area for increased investment and focus.
After Naim Alkhouri describes some of the differences between resmetirom and semaglutide in terms of practical treatment decisions, the discussion focuses on why MASLD and MASH will create unique challenges for hepatology practices. Manal views the issue as a matter of time; practices cannot absorb large numbers of new, non-urgent patients. Naim suggests that the real issue is the business question: specialists today do not profit simply from treating patients. Zobair agrees with Naim and notes that the challenge is not unique to hepatology. He expresses the hope that AI and efficient database management will make it easier to target, screen, diagnose and treat patients...given sufficient providers (mostly APPs) to treat them.
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Key Opinion Leaders Manal Abdelmalek, Naim Alkhouri, Scott Isaacs and Zobair Younossi join Roger Green to discuss FDA's approval of semaglutide for patients with non-cirrhotic MASH. This conversation focuses on benefits for patients and ways that having two drugs with different modes of action will change pharmacotherapy choices.
This conversation starts with the group describing the sense of "enthusiasm" and "fulfillment" hepatology drug developers feel to see two drugs approved in the US and many other major changes to come (more drug approvals, FDA acceptance of a path to approval that is not based on liver biopsy). One interesting takeaway is that while the approval of semaglutide will likely change the number of patients treated with MASH pharmacotherapy, the greater impact of this approval will be on public awareness of MASH and the accompanying demand for treatment. In terms of actual drug use, the first major change will come among patients living with obesity but not Type 2 diabetes. Most of these patients previously saw their semaglutide prescriptions rejected for payment by health insurers. However, many of these patients will be living with MASH, and they are likely to see their prescriptions approved.
Instead, the largest impact may involve increased education and awareness. Scott pointed out that endocrinologists, who frequently prescribe incretin agonists, will have reason to learn how to diagnose and manage MASH in patients they already treat. Zobair noted that an array of companies, starting with pharmaceutical manufacturers and scanning companies, will dramatically increase investments in prescriber and patient education.
Another important benefit may come in terms of coverage. Scott points out that most patients living with obesity but not diabetes are unlikely to have their semaglutide prescriptions covered by commercial insurers. Those living with non-cirrhotic MASH are likely to have semaglutide covered. A separate but related point: Naim reports that ~30% of the MASH patients he sees are taking an incretin agonist at the time of initial visit.
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00:00:00 - Surf's Up, Season 6, Episode 12
This week's episode is a special three-part roundtable on the implications of the FDA's recent approval of semaglutide. Naim Alkhouri, Manal Abdelmalek, Scott Isaacs and Zobair Younossi join Roger Green in a discussion that focuses less on specifics of pharmacotherapy and more on how having two drugs available will change MASH management in the US.
00:08:45 - Part I: How Will The Semaglutide Approval Affect Patient Treatment and Pharmacotherapy?
The group starts by describing the sense of "enthusiasm" and "fulfillment" hepatology drug developers feel to see two drugs approved in the US and many other major changes to come (more drug approvals, FDA acceptance of a path to approval that is not based on liver biopsy). One interesting takeaway is that while the approval of semaglutide will likely change the number of patients treated with MASH pharmacotherapy, the greater impact of this approval will be on public awareness of MASH and the accompanying demand for treatment. In terms of actual drug use, the first major change will come among patients living with obesity but not Type 2 diabetes. Most of these patients previously saw their semaglutide prescriptions rejected for payment by health insurers. However, many of these patients will be living with MASH, and they are likely to see their prescriptions approved.
Instead, the largest impact may involve increased education and awareness. Scott pointed out that endocrinologists, who frequently prescribe incretin agonists, will have reason to learn how to diagnose and manage MASH in patients they already treat. Zobair noted that an array of companies, starting with pharmaceutical manufacturers and scanning companies, will dramatically increase investments in prescriber and patient education.
00:25:30 - Part II: How the Structure of Medical Practice Is Likely To Change
Naim states that many hepatologists are currently uncomfortable managing patients on GLP-1 agonists. This will need to change. Manal points out that providers must check for cirrhosis while testing for MASH and understand how to respond. An increase in the number of providers having access to in-office scanning devices will facilitate this process. Zobair states that even if all the related specialists integrate MASH into their practices, the actual patient care demand will require alternate pathways in which the responsibility for patient care will rest with specialist APPs.
After Naim Alkhouri describes some of the differences between resmetirom and semaglutide in terms of practical treatment decisions, the discussion focuses on why MASLD and MASH will create unique challenges for hepatology practices. Manal views the issue as a matter of time; practices cannot absorb large numbers of new, non-urgent patients. Naim suggests that the real issue is the business question: specialists today do not profit simply from treating patients. Zobair agrees with Naim and notes that the challenge is not unique to hepatology. He expresses the hope that AI and efficient database management will make it easier to target patients, screen, diagnose and treat them.
00:44:17 - Part III: What Happens Next?
In this final section, panelists identify some of the changes they foresee if we are to manage the tsunami of undiagnosed MASLD patients. Many of the comments touch on themes discussed earlier in this episode, but a couple are unique. Zobair states we must remember that the vast majority of MASLD patients will never develop MASH. Manal foresees a more sophisticated approach to selecting pharmacotherapies as prescribers have a broader set of options, each with its own benefits and drawbacks. Scotts anticipates a "paradigm shift" in which endocrinologists view MASH similarly to how they view retinopathy, neuropathy and retinopathy.
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This week's expert interview is with Dr. Emily Andaya, Medical Director of the Cardiovascular Program at Major Health Partners of Shelbyville, IN. She joins Louise Campbell and Roger Green to discuss the American Heart Assocation's CKM initiative, why she believe it should be titled "CKLM" for liver, and how including liver in the CKM scoring system would make it stronger and provide a more robust tool to help improve patients' health.
Emily begins by discussing her attendance at the American Society for Preventive Cardiology meeting in Boston the previous weekend, where Dr. Christos Montzoros presented a talk proposing that the liver's role in cardiovascular diseases is "equally critical" compared to the kidney and other multi-metabolic co-morbidities. Dr. Montzoros closed his talk by stating that the CKM syndrome description should be changed to CKLM to reflect the importance of the liver, and that the CKLM patient scoring and criteria should reflect this as well.
Next, Emily describes the 0-to-4 scoring system that the CKM initiative has chosen to use and the recommendations that accompany the scoring system itself. The system does not neatly overlay the 4-point fibrosis scoring system or the NAS score, but Emily describes how these might be incorporated into the CKM score.
The conversation shifts to focus on patient management. Since the original CKM paper was published in 2023, resmetirom had not yet been approved and the paper itself focused more on screening than on treatment. To Emily, adding the "L" to CKM would entail adding resmetirom to treatment protocols as appropriate, and also considering drug combinations that addressed liver disease. Louise takes this issue from the other side, suggesting that every time a provider prescribes a drug to a CKM patient, the potential for negative liver effects should be part of the selection process. Emily and Louise agree that providers and patients should take a holistic approach to therapy for these patients. One benefit: even if a patient has multiple organs affected by multi-metabolic challenges, the provider can educate the patient that there is a single target disease to treat instead of multiple different diseases. As Roger notes, treating 4-5 discrete diseases simultaneously sounds overwhelming, while treating one overarching disease sounds far more manageable.
The conversation ends with a focus on whether we are correctly identifying high-risk cardiovascular patients in the current environment, and how this more holistic focus might improve patient screening and identification.
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Multi-Metabolic Week focuses on the idea that MASLD and MASH are elements in a systemic set of Multi-Metabolic issues. This conversation is the second of two looking at the concept of the "Multi-Metabolic Clinic," a clinic that treats the entire spectrum of multi-metabolic diseases.
This conversation starts by focusing on how the two clinics train other physicians and practices on multi-metabolic issues. The EDOM clinic in Spain is certified to provide nutritional training to other practices across the country, while the newer, smaller Trajectory Health Partners practice provides support on use of FibroScan and, more recently, Velacur from Sonic Incytes. Louise notes how important training is for optimal use of scanning devices, which includes both technical proficiency and knowledge of how to educate and motivate patients using the results of the scans.
From there, the conversations shifts to focus on differences between treating patients in a conventional practice vs. a multi-metabolic one. The key differences involve length of patient visit and use of allied providers to educate patients more fully. Next, Louise asks whether the clinics have data on reducing the number of patients needing to go to a hospital. EDOM has data while the younger Trajectory has a clear sense this happens but no large-scale practice data to support this sense.
Louise's last question is to ask how each physician would "sell" colleagues in their specialty on why to set up a multi-metabolic practice. The answers reflect the different specialties in which the physicians were trained originally (endocrinology in Spain, gastroenterology in the U.S.) but have significant common elements.
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Multi-Metabolic Week focuses on the idea that MASLD and MASH are elements in a systemic set of Multi-Metabolic issues. This conversation is the first of two looking at the concept of the "Multi-Metabolic Clinic," a clinic that treats the entire spectrum of multi-metabolic diseases.
The core of this episode starts during the weekly groundbreaker exercise, during which our guests began to describe the path that brought them from single-disease specialization to the broader multi-metabolic practice.. Immediately after the groundbreakers, participants describe their clinics today, including patient population and principles underlying their approach to treatment.
For Karen, the path started in a conventional gastrointestinal practice. A decade ago, she gained certification in obesity medicine. While treating patients for obesity, she came to appreciate the interplay of obesity, diabetes and the other manifestations of multi-metabolic disease. Eventually, she divided her practice and time so that she spent half her time in the GI practice and the other half creating Trajectory Health Partners, a practice focused on overall metabolic health.
For Dr. López, the initial goal was to "re-educate the hypothalamic problem," which he saw as the root cause of obesity and from which all other metabolic issues came. He describes this as "the auto-destruction button" of patients' lives, leading to two causes of death: (1) insulin resistance and related cardiovascular problems, and (2) short-telomere cancers.
The rest of this conversation focuses on the tests that the two clinics use to confirm MASLD or MASH and their approaches to treating multi-metabolic patients.
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00:00:00 - Surf's Up: Season 6, Episode 11
This week, we modify our usual episode structure to focus on multi-metabolic practices and constructs. The multi-metabolic practices covered this week are run by non-hepatologists who have chosen to focus on the liver in a broader cardiometabolic context. They include two practices discussed during a two-part roundtable, one run by US gastroenterologist Dr. Karen Jerome-Zapadka and the EDOM practice in Spain, run by endocrinologists. The expert interview is with Dr. Emily Andaya, an internist who helms a cardiometabolic practice in Indiana, US, that focuses on the liver.
00:14:23 - Roundtable Part I: Groundbreaker and introduction
The core of the episodes started during the weekly groundbreakers, as guests began to describe the path that brought them from single-disease specialization to the broader multi-metabolic practice.. Immediately after the groundbreakers, participants describe their clinics today, including patient population and principles underlying their approach to treatment.
00:26:15 - Roundtable Part II: Tools they use
Guided by Louise, the specialists discuss the devices they use to screen and stage patients and the drugs they use to treat them. One interesting item that emerges is that EDOM relies on a 0-to-4 disease severity classification, but it does not align point-by-point with the 4-point fibrosis scale common in MASH.
00:40:28 - Roundtable Part III: Training Providers in the Clinics
Louise starts this segment by asking the EDOM team how they train practitioners in their clinic. EDOM trains practitioners in nutrition and technologists in the proper use of scanning devices. Karen comments that one big issue in re-training involves the length of visits: 15 minutes for a typical GI visit vs. 60 minutes for an initial multi-metabolic session and 30 minutes for follow-ups. Along with this, the information gathering technique are different.
00:50:57 - Roundtable Part IV: Patient Health and Wrap-up
Louise asks participants whether and how they have measured the impact the multi-metabolic approach has on patients' health (profound in both cases) and whether they are seeing an increase in HCC. Karen sees a difference among her long-term patients, while EDOM refers patients before their fibrosis reaches cirrhosis stage.
In the last part of the episode, panelists share perspectives on how their initial specialties fit with the broader multi-metabolic practice and the kinds of impact they can have on patients.
01:12:50 - Expert: Dr. Emily Andaya discusses US initiatives in multi-metabolic health
This week's expert is Dr. Emily Andaya, an Indiana (US)-based internist whose practice has expanded to take on a multi-metabolic focus. She begins by discussing her recent attendance at the American Society for Preventive Cardiology (SPC) meeting in Boston, where she heard a talk by Dr. Christos Montzoros, an endocrinologist and multi-metabolic advocate, who emphasized the importance of incorporating the liver into preventive cardiology's focus. Louise and Emily agree that cardiometabolic focus involves evaluating general, overall health, but Emily discusses how this might require a deeper or broader testing protocol for each target organ. Emily describes the 4-point CKM scale and Louise asks how fibrosis or NAS scoring, as deployed in the MASH CRN system, might be valuable here. This is a far-ranging conversation, but one special point of interest involves the psychological benefit of telling a patient they need to treat one (multi-metabolic) condition, instead of separate heart, kidney, endocrinological and liver conditions, which might feel far more overwhelming.
01:48:48 - Conclusion
Because Roger is on vacation, there is no business report this week.
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This week's expert is Tim Jobson, Medical Director of Predictive Health Intelligence, a UK-based consultancy. Tim joins Louise Campbell and Roger Green to share an update on PHI's Somerset UK project and other activities.
The Somerset pilot was designed to help the NHS identify untreated patients at high risk for liver disease and bring them to the office for screening. Tim describes hepatoSIGHT, a tool that "allows clinicians to get their hands on the data and to find patients both for treatment and for clinical trials." He describes it as standard in Somerset, UK, now, and proceeds to share new data about the patient experience. This is a unique program in that providers reach out to tell individual patients they should visit the physician based on information found in their medical records. Interestingly, patient response is overwhelmingly positive. Louise shares data indicating that 94% of individuals located by the NHS in this manner visited their GPs. Six in ten respondents rated their satisfaction with the process, giving it a mean of 4.8 on a 5-point scale. Tim also shared some preliminary modeling suggesting that sustained use of hepatoSIGHT could increase clinical trial participation as much as 50-fold if trial sites had the capacity to take all these patients.
Based on the results of the pilot, hepatoSIGHT is now standard throughout the Somerset region and is being evaluated for broader use. Tim and Louise both point out that this represents a major advance in the applied use of preventive hepatology. In all, this is a warming, affirming look at whether and how patients know they benefit from what we ask them to do and share.
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Roger Green talks with LiverRight CEO Brandon Tudor and Chief Medical Officer Alexander Lalos about the launch of LiverRight, America's first virtual hepatology clinic, which has recently begun treating patients.
Brandon starts the conversation by telling the story of how he and his partner, Pete Celano, started LiverRight: they saw liver disease as a growing disease in a medical system that was ill-equipped to provide front-line care. When the two men "secret shopped" getting doctor's appointments, they found extremely long waits (3-5 months in examples provided throughout this conversation) for appointments that put stress on the patients and their schedules (days off from work, hours of travel to the clinic). Brandon gave one example in Arizona, where LiverRight could get a hepatologist certified and accepted by insurance months faster than the patient could get an appointment at a local hepatology center.
Al amplifies the issue by noting that when the patient in Arizona was scheduled to see a transplant hepatologist, who certainly could treat the patient but was "not really appropriately matched to [the patient's] condition. To Al, who is a transplant hepatologist himself, the virtual approach provides three benefits: convenience, speed and a better match between provider and disease. As Al notes, transplant hepatologists spend their time doing transplants, an important and highly specialized skill. A far broader swath of providers could treat a patient seeking testing for MASLD.
Al notes two more benefits he sees with virtual clinics. After online triage during the initial visit, the patient is routed to the level and type of provider best matched to that individual's need for care. The second benefit, which Al says "may sound crazy," is that an online visit, where the provider is looking directly at the computer (and patient) while entering information, feels far more personal than an in-person visit where the provider is looking at the computer monitor instead of the patient.
The rest of the discussion covers various advantages that the LiverRight executives believe accrue from virtual care. The most important, in Brandon's words, is that virtual "allows us to move to a preventive world instead of a reactive world." One that Al mentions is that the quality and breadth of knowledge of the virtual providers is higher than he expected and leads to both guidelines that are appropriate to task and special knowledge in key areas such as nutrition.
NOTE: Roger Green is a paid advisor to LiverRight
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This conversation is the first segment of SurfingMASH’s July discussion of key events from the first six months of 2025. Co-hosts Jörn Schattenberg, Louise Campbell and Roger Green each chose one topic of personal interest. Today, Jörn Schattenberg discusses two recent papers that demonstrate differences in how individual patients respond to different proteomic tests and what this can mean for individualized treatment plans.
Jörn begins by citing Modulation of megabolic, inflammatory and fibrotic pathways by semaglutide in metabolic dysfunction-associated steatohepatitis, a paper from researchers at Novo Nordisk that Nature magazine posted online on July 21. In this paper, the researchers utilized proteomic testing (aptamer-based SomaSignal NASH tests) to determine whether semaglutide successfully addressed different NAS score elements: steatosis, lobular inflammation, hepatocyte ballooning and fibrosis. The proteomics-based tests indicated an improvement in all four of these elements, but the elements that improved and the amounts of improvement varied among individuals. To Jörn, this suggests that we can use an individual patient's proteomic results to tailor individualized therapy based on the areas in need of improvement, so that the prescriber would know whether the best approach to resolve NAS and reduce fibrosis was one that focused on metabolic issues vs. specific anti-fibrotic effects in the liver. He supports this idea by referring to a paper he had published in JHep Reports. In this paper, he and his colleagues looked at semaglutide Phase 1 and 2 obesity trials, where MASLD was not a criterion for entry. However, analyzing individual patients with the SomaLogic panel revealed that many had some form of MASLD and that semaglutide therapy could resolve the specific MASLD issues.
The rest of the conversation focused on Jörn's conclusion and the potential for tailoring treatment plans to the individual. Lousie hailed the entire concept as extremely helpful not only in selecting a pharmacotherapy but also in providing patients with information they could use to improve their health further. Roger suggests that the kinds of proteomic tests Jörn describes can lead to first-line multi-agent pharmacotherapy to address the disease with agents that collectively will address the individual patient's profile.
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00:00 - Surf's Up 6.10.1
This conversation covers three topics. Jörn Schattenberg discusses two papers that suggest an exciting role NITs might play in future prescribing decisions, two executives from LiverRight describe the U.S.'s first virtual liver clinic, and Tom Jobson of Predictive Health Intelligence updates us on how simple analyses of large data bases can identify and motivate high-risk liver patients to visit their doctors.
00:17:30 - Roundtable: NITs might help physicians determine the value of metabolic vs. specific anti-fibrotic effects for individual patients
The overall theme of this roundtable is "Major Stories and Events of the First Half, 2025." Jörn's contribution is to discuss two papers that use proteomic analyses to determine the degree to which a patient's MASH is driven by metabolic issues as compared to direct fibrotic challenges. Today, when we have only a few drugs, limited NITs and no proteomic tests available for use in practice, these findings point to directions for future research and test development. Over time, providers may be able to prescribe based on the knowledge of h0w much benefit metabolic agents might provide as compared to anti-fibrotics. This may point to step therapy or multi-agent first line therapy, but it is an exciting idea.
00:29:50 - Newsmakers: LiverRight opens America's first virtual liver clinic
LIverRIght CEO Brandon Tudor and Chief Medical Officer Alexander Lalos join Roger Green to discuss the launch of America's first virtual hepatology clinic. Brandon shares his personal history to explain why providing fast access is so important to him. Alex describes his original motivation to go into Transplant Hepatology and how, over time, his focus has shifted from healing the sick to preventing disease in the first place. They describe how LiverRight works and their successes to date in reducing patients' time from first contact to visit, often from months to days. NOTE: Roger Green is a paid advisor to LiverRight.
00:56:44 - Expert: Tim Jobson describes how Hepatoscope is helping the NHS identify untreated high-risk liver patients and bring them to the office for screening. Tim describes hepatoSIGHT, a tool that "allows clinicians to get their hands on the data and to find patients both for treatment and for clinical trials." He describes it as standard in Somerset, UK, now, and proceeds to share new data about the patient experience. This is a unique program in that providers reach out to tell individual patients they should visit the physician based on information found in their medical records. Interestingly, patient response is overwhelmingly positive. Six in ten respondents rated their satisfaction with the process, giving it a mean of 4.8 on a 5-point scale. Tim also shared some preliminary modeling suggesting that sustained use of hepatoSIGHT could increase clinical trial participation as much as 50-fold if trial sites had the capacity to take all these patients. In all, this is a warming, affirming look at whether and how patients know they benefit from what we ask them to do and share.
01:29:58 - Conclusion
The business report discusses the next few episodes and asks who would like to meet Roger at Paris MASH.
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Hepatologist and hepatology key opinion leader Naim Alkhouri joins Roger Green to remember his longstanding relationship with Stephen Harrison, announce his new role as Chief Academic Officer at Summit Clinical Research and share how, in this role, he will have exciting new avenues make an impact on many elements of MASH drug development and patient care.
The conversation can be divided into two sections. In the first, Naim recounts his relationship with Stephen Harrison, beginning with his move to a different San Antonio clinical trial practice and continuing through his tenure at Arizona Liver Health, up until Stephen's untimely passing last April. He describes what it was like to work with Stephen, the man, and to learn from and share ideas with Stephen, the "visionary."
Next, Naim announces that he has joined Summit Clinical Research as Chief Academic Officer. He describes the many aspects of his new role, from collaborating with Gail Hinkson, Mazen Noureddin and the rest of the Summit team in designing better clinical trials to the many kinds of medical education Summit can bring to various medical stakeholders. He describes the dramatic growth in the number of trial sites in the Summit network and additional growth he foresees. Like Gail Hinkson in the same episode, he discusses ways in which Alzheimer's drug development is similar to MASH. He also touches on obesity trials and the ways that Summit can help create more robust knowledge about obesity, not only through trials but also expert advisory boards. In the end, he makes a personal announcement that you will have to read to learn.
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Fatty Liver Alliance President Mike Betel joins Roger Green to discuss his recent completion of the 3rd Annual Glucose Challenge, an event every July where Mike wears a continuous glucose monitor (CGM) device for a month, conducts food experiments, tracks glucose levels and shares all results with his LinkedIn and FattyLiver.ca friends and followers.
The conversation starts with Mike sharing the history of the Glucose Challenge. Over its first three years, it has evolved from a means to demonstrate the adverse effects of certain foods on human glucose levels into a shared lesson on how a patient (in this case, Mike) can maintain his blood glucose level between 75 and 140 mg/dl.
During the episode, Mike shares some of the tricks he has learned to manage glucose more effectively. The most intriguing one? To manage post-prandial (after-meal) glucose levels, walk for "10, 15, 20, 30" minutes after each meal. An obvious and simple one many of us forget? "You don't have to finish everything put in front of you," and you shouldn't feel guilty about not finishing later. A cautionary note: weight loss via diet or drugs without exercise can lead to a greater loss in muscle or bone mass than in fat, but it does not take much in terms of formal exercise to maintain muscle and bone while dropping fat.
Mike also applauds ChatGPT and an array of consumer health devices for giving him the data and analytical support he needed to track key body metrics and know how to act upon them.
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This conversation is the third and final segment of SurfingMASH’s July discussion of #SLDThinkTank 2025. In addition to co-hosts Jörn Schattenberg, Louise Campbell and Roger Green, panelists include Dr. Kristina Curtis of Applied Behaviour Change, a UK-based consultancy.
Louise begins this conversation by highlighting the low level of correct information (and, frequently, high level of passionately-held misinformation) that adults have about diet and her success in improving a family's behavior by educating parents about how to better help their children. Kristina replies that while knowledge and education are critical, they are not sufficient in themselves. She lists a variety of social or life priority factors that can also drive poor eating, from taking out fast food when too hungry to cook to not wanting to fight with one's children about eating their vegetables to comparing themselves to other, more obese friends or acquaintances.
Roger asks about the role politicians can play on these kinds of issues. Jörn observed that politicians at the Think Tank were motivated to act and thought about how to support better behavior. Louise noted that multi-metabolic programs with broad support can help many MASLD patients, even though MASLD is not in the stated goal for the program. Roger and Kristina note that politicians and government budget manager are motivated by short-term solutions with little thought to longer term consequences.
In the last part of this conversation, Roger asks the group to describe their reactions leavin the Think Tank in a single word. Louise and Kristina both choose "enlightened." Jörn chooses "inspiring" to describe Louise's comments and "motivating" to describe his own reaction. Listen to the conversation to hear the reasoning behind these word choices.
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00:00:00 - Surf's Up: Episode 6.9
This conversation covers three topics. The first discusses the challenges of behavior change in dietary habits and ways governments can help, the second looks at what one can learn from wearing a CGM for 30 days, and the third celebrates the late Stephen Harrison while looking into the future of clinical trials and medical education.
00:06:12 - Global Think-Tank on SLD Roundtable, Part 3
Behavior consultant Dr. Kristina Curtis joins Jörn Schattenberg, Louise Campbell and Roger Green to discuss issues related to patient-centered care. This conversation starts by focusing on the unique challenges that come with changing dietary habits. Changing this behavior is so challenging because the issues are so complex. People lack education about healthy eating habits. Even when they do, the high-pressure world in which we live often makes it easier simply to offer children fast food. Even parents who know better might allow their children (or spouses, or selves) not to eat vegetables after a trying day. The panel proceeds to discuss steps politicians can take to encourage healthier living and lifestyles if they wish, and why some are easier to execute than others. Finally, the group shares why they felt "enlightened" when leaving the SLD, and perhaps a little less alone.
00:21:34 - Newsmaker: Fatty Liver Alliance President Mike Betel
This interview with Fatty Liver Alliance President Mike Betel focuses on Year 3 of his 30-day Glucose Challenge. Mike wears a continuous glucose monitor (CGM) for the entire month of July and provides daily videos on LinkedIn and the Fatty Liver Alliance website discussing what he learned. The first year was dedicated to teaching the impact of eating badly and the second year was similar, but less egregious. This year, Mike, who is pre-diabetic, set the goal of keeping his glucose in a "normal" range of 70-140 mg/dl. He did so successfully 97-98% of the time over the month, and discusses some of the tricks he learned that help keep glucose in range over that time (HINT: walking 10-15 minutes after meals helps a lot!). He also shares hints about how to look at overall weight (it's the fat that matters, not simple weight), why it is not healthy to believe you must finish every bite of food put in front of you, and how all this relates to sleep and overall health. He also provides seeds for thought about ways manufacturers and providers might educate patients effectively on these issues.
00:53:11 - Expert: Summit Clinical Research Chief Academic Officer Naim Alkhouri
This interview occurred in late April during our episode celebrating Stephen Harrison. Naim chose this interview to annouce that he was joining Summit as Chief Academic Officer. The first part of this discussion focuses on Stephen on two levels: the personal history between Naim and Stephen and the nature of the contributions Stephen has made to the science of MASH, and particularly clinical trial design. The second part of the interview discusses Naim's new role, the diffrent kinds of teaching, training and medical education he sees as pivotal to the future of MASLD and MASH therapies, and the other elements of his new role. While discuss the role, he shares several bright, challenging insights about when MASH-ville is heading.
01:15:09 - Conclusion
The business report discusses vacations on the SurfingMASH team, upcoming episodes, and grateful notes from Ukrainian listeners.
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This conversation is the fourth and final segment of SurfingMASH’s April discussion of drug development in memory of Stephen A. Harrison. In addition to co-hosts Jörn Schattenberg, Louise Campbell and Roger Green, panelists include hepatologist and key opinion leader Sven Francque.
The discussion focuses on PPARs, genetic medicines, and other emerging drug classes while considering the idea that drug therapies can have an impact on the liver independent of their effect on fibrosis regression. It begins with Sven discussing his experience as a lead investigator in clinical trials for the pan-PPAR agonist lanifibranor, whose Phase 3 trial is now fully recruited. Sven states that in addition to fibrosis regression, lanifibranor is likely to exhibit other pleiotropic effects, and notes that vascular changes start early in the fibrotic progression process.
After Sven elaborates on these effects, Louise asks about the SCD-1 agent Aramchol. This leads to a discussion about the idea that over time, therapy will probably come to incorporate two separate modes of action, with one to treat the metabolic dysfunction and the other to treat specific effects in the liver or, as Jörn puts it, "combining weight-neutral and weight-reducing drugs." This evolves into a discussion of what Louise terms "personal-centric" medicine, or what patient advocate Mike Betel has previously described on SurfingMASH as "tailored medicine."
The rest of the conversation predominantly lists other classes of drugs, "safe" mitochondrial uncouplers, genetic medicines, and others. Roger inquires about the FASN inhibitors, which are entering Phase 3 clinical trials. Jörn says that the data appears positive and unique. That said, he and Sven agree we need more data.
Louise sounds the closing note for this roundtable by discussing our co-founder, Stephen Harrison, and the energy and enthusiasm he brought to the entire drug development process. The group agrees that Stephen's impact continues to be felt through the MASLD community, even as he is missed by us all.
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Global Liver Institute President and CEO Larry Holden joins Roger Green to discuss recent Washington political and regulatory activities, their potential impact on the liver community, and ways we can respond.
Larry starts by acknowledging that we are in for "dark times" under the current administration and describes some current government actions that are causing major setbacks, as well as others that have the potential to do so. Specifically, he details the challenges caused by budget cuts, reallocation of funds away from major universities, staff reductions and, along with them, a loss of expertise in technical areas where knowledge and experience are pivotal.
Without minimizing these challenges, Larry proceeds to suggest actions that individuals and organizations can take to reduce losses to the greatest extent possible — and even create some "wins" — for people living with liver disease. He describes tactics for giving legislators something they value (mainly publicity and contacts) to build a relationship, gain access and create a sympathetic ear for liver community messages.
The conversation itself shifts back and forth between some of the current challenges and the steps advocates can take to mitigate losses and, whenever possible, achieve "wins." Sometimes discouraging, sometimes educational, this is an essential conversation for all current and potential advocates for liver patients to hear.
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This conversation is the second segment of SurfingMASH's coverage of the Global Think Tank on Steatotic Liver Diseases (#SLDThinkTank2025) held in Barcelona in June. It focuses on the kinds of feedback most likely to produce successful behavioral interventions.
The conversation begins with Jörn discussing the Liver Screen Study, a "very ambitious effort" that starts with 30,000 members of the general European population, narrows down to a subgroup with liver disease, and then provides these individuals with information about MASLD and how to manage it, ultimately evaluating its impact. Many of these people did not know about liver disease before being informed they had it, and many changed their behavior as a result. Jörn links this to the EASL Amsterdam activity discussed last week in 6.7.1 and 6.7.2.
Louise relates a story of speaking with Laurent Sandrin, Chairman of Echosens and inventor of FibroScan, who was "blown away by the reaction" to making FibroScans available and promoting this fact. Louise explained to Laurent that from her vantage point, FibroScan is "more than just the physical diagnostic. It has the power to engage populations," and, for many, provide the information and motivation they need to change behavior. Kristina describes how we can provide "biofeedback" like this, along with other behavioral strategies, to produce sustainable behavior change, which is far harder for an individual than simply reacting to a medical scare. She describes a model she deploys, the "Combi" model, which integrates an array of informational, motivational and behavioral items into an integrated, individualized approach.
The conversation shifts to focus on environmental factors that work against long-term change. For someone with alcohol use disorder, this might be a family member who continues to consume large quantities of alcohol frequently. For someone living with obesity, it might be a favorite high-calorie dish...or even simply food advertising.
In the final part of this conversation, Jörn states that the Think Tank steering committee invited politicians to help them understand why certain kinds of interventions — such as taxing medically harmful goods or limiting advertising — might be socially valuable, even if unpopular. The group discussed some governmental tactics that are effective and others that are not.
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00:00 - Surf's Up, Season 6 Episode 8
The conversation addresses three issues that are distinct, yet each is pivotal to the future of MASLD and MASH therapies. The first, from the Global Think-Tank on Steatotic Liver Disease, considers how personal and digital approaches can be combined to form the most effective strategy for patient management. In the second, Global Liver Institute President and CEO Larry Holden joins Roger Green to discuss the new challenges in Washington stemming from the Trump Administration and RFK Jr. The final section is the conclusion of our recent drug development roundtable, examining drug classes we did not previously discuss, along with a thought on where combination therapy is likely to lead.
00:04:57 - Global Think-Tank on SLD Roundtable, Part 2
Behavior consultant Dr. Kristina Curtis joins Jörn Schattenberg, Louise Campbell and Roger Green to discuss issues related to patient-centered care. This discussion focuses on the elements of successful behavior change and the importance of real-time, actionable feedback. The group discusses the interplay of diagnostic test feedback, real-time personal exchanges and AI-based algorithms in what Kristina terms a "hybrid therapy."
00:18:39 - Newsmaker: Larry Holden
GLI President and CEO Larry Holden addresses two issues related to current goings-on in Washington. First, he acknowledges that we are in for "dark times" under the current administration, and describes some of the decisions and challenges we face. Second, he suggests what individuals and organizations can do to create the best possible situation -- and even some "wins" -- for people living with liver disease. These suggestions reflect his experiences during a 30-year career on Capitol Hill, prior to his joining GLI.
00:46:15 - Drug Development Roundtable, Part 4
Sven Francque joins Jörn, Louise and Roger to share an up-to-date look at drug development. This discussion focuses on PPARs, genetic medicines, and other emerging drug classes. Sven uses the example of the pan-PPAR lanifibranor to explore the idea that drug therapies can have an impact on the liver independent of their effect on fibrosis regression. The group proceeds to discuss other emerging drugs in development and their modes of action. One theme: over time, we may see prescribers consider using different therapies to address metabolic vs. liver-specific effects, often in combination.
01:00:47 - Business Report
Thanks to our listeners, Jörn's vacation, Welcome Regeneron
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This conversation is the third segment of SurfingMASH’s April discussion of drug development in memory of Stephen A. Harrison. In addition to co-hosts Jörn Schattenberg, Louise Campbell and Roger Green, panelists include hepatologists and key opinion leaders Sven Francque and Naim Alkhouri.
Louise starts the discussion by asking when a patient is metabolically and hepatically healthy instead of merely driving weight loss. She notes that basing therapy entirely on weight loss goals will breed failure and frustration while failing to address the actual pivotal goal of metabolic health. Sven agrees and notes how important this point is. Roger suggests that the benefit of weight loss is likely to become limited over time, which is why there is such excitement about GLP-glucagon combination therapies. Again, Sven concurs, noting that such knowledge and increasing drug class diversity will allow researchers to look at true, basic differences between agents instead of "small numerical differences."
Jörn notes the importance of NITs in addressing these kinds of issues. Scanning is an effective method for measuring changes in liver fat; however, the academic community has developed surrogate NITs for specific physiological activities. As Sven notes, there is still a great deal of work to do here. That said, Jörn cites examples of large, NIT-based projects like the VCTE Study Group that have sufficient sample size to start building definitions around kilopascal levels. Louise shares her strong concern that many TE operators are not trained adequately to appreciate subtle clues that would tell an expert how an individual scan was providing misleading results. She notes that the increased demand for scanning, in this case TE, is going to drive a watering down of the qualifications and the skill of the user and the supervision level..." The discussion winds down with Sven agreeing with Louise and stating the need for sequential testing and Jörn citing EASL guidelines in stating that practices should provide and manage high-quality care to the best of their abilities.
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This week's newsmaker, Dutch Liver Patients Association President Jose Willemse, joins Roger Green to discuss the patient screening program at this year's EASL Congress, which took place in Amsterdam, and the general idea of what constitutes a patient-sensitive dialogue.
Jose describes the phenomenal level of interest in the screening activity, in which hepatologists and APPs scanned 400 people per day for MASLD and MASH. Boosted by significant mass publicity in Amsterdam, the number of people seeking screening exceeded the 400/day quota, with some arriving in line hours before the scheduled start time and others traveling for hours to reach the site. Jose believes that with adequate publicity, efforts like these could be replicated around the world, but that the healthcare system lacks the necessary resources to do so. In terms of physician-patient dialogues, Jose emphasized the importance of sensitive yet frank conversations and helping patients appreciate the successes they are achieving.
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This conversation is the opening segment of SurfingMASH's coverage of the Global Think Tank on Steatotic Liver Diseases (#SLDThinkTank2025) held in Barcelona in June. Co-hosts Louise Campbell and Roger Green are joined by Dr. Kristina Curtis, Managing Director of Applied Behaviour Change, a UK-based consultancy.
This discussion starts with co-host Jörn Schattenberg discussing the history and evolution of the first four Global Think-Tanks as the focus shifts from educating medical professionals about liver disease to incorporating a broader group of stakeholders, including politicians and non-hepatologist MDs, to break down siloes and create broader awareness. Co-host Louise Campbell describes the breadth of stakeholders necessary to address this pandemic fully. She explains how her work with transient elastography and the MyLife365.me app constitutes a form of behavioral therapy. Jörn describes the test as a diagnostic and comments that the treatment is what health professionals do with the results. Kristina says that the behavioral change that results comes from well-delivered feedback. She describes "hybrid interventions, digital interventions with a human in the loop." Louise discusses results from the EASL late-breaker that support these findings and goes on to discuss the role AI can play in medical practices.
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00:00:00 - Surf's Up: Season 6 Episode 7
Host Roger Green explains our recent vacation from publishing episodes, assures the audience that the podcast will continue weekly for months and years ahead, and discusses the episode's sections, covering the Global Think-Tank on Steatotic Liver Disease (SLD), the EASL patient screening activity and the increasing role of NITs in drug development. While introducing roundtable guests, he introduces first-time Surfer Dr. Kristina Curtis of the UK-based consultancy, Applied Behaviour Change.
00:09:11 - Roundtable I: From the Global Think-Tank on SLD
This discussion starts with co-host Jörn Schattenberg discussing the history and evolution of the first four Global Think-Tanks as the focus shifts from educating medical professionals about liver disease to incorporating a broader group of stakeholders, including politicians and non-hepatologist MDs, to break down siloes and create wider awareness. Co-host Louise Campbell describes the breadth of stakeholders necessary to address this pandemic fully. She explains how her work with transient elastography and the MyLife365.me app constitutes a form of behavioral therapy. Jörn describes the test as a diagnostic and comments that the treatment is what health professionals do with the results. Kristina says that the behavioral change that results comes from well-delivered feedback. She describes "hybrid interventions, digital interventions with a human in the loop." Louise discusses results from the EASL late-breaker that support these findings and goes on to discuss the role AI can play in medical practices.
00:23:50 - Newsmaker: Jose Willemse, Dutch Liver Patients Association
This discussion covers two primary topics: (1) the Amsterdam screening activity that took place during EASL. Jose describes the phenomenal level of interest in this activity, in which hepatologists and APPs scanned 400 people per day for MASLD and MASH. Boosted by significant mass publicity in Amsterdam, the number of people seeking screening exceeded the 400/day quota, with some arriving in line hours before the scheduled start time and others traveling for hours to reach the site. Jose believes that with adequate publicity, efforts like these could be replicated around the world, but that the healthcare system lacks the necessary resources to do so. In terms of patient care, Jose emphasized the importance of sensitive yet frank conversations and helping patients appreciate the successes they are achieving.
00:53:45 - Roundtable II: NITs Increasing Role in Drug Development
Sven Francque and Naim Alhouri joined Louise, Jörn and Roger for this roundtable, although Naim had dropped off by this time. The conversation starts with Louise noting that the goal of therapy is not simply to treat MASLD, but to achieve overall metabolic health, of which MASLD is a key component. Jörn states that we are on the path toward conducting clinical trials entirely with NITs as disease markers, which he describes as a "game changer" and Louise terms "exciting." She asks whether NITs can serve as the only trial surrogate. Jörn and Sven agree that we are not at that point yet, but we are headed in that direction. Jörn asserts that "nothing" will replace outcomes as the prerequisite for full approval and mentions the VCTE study group as demonstrating that a large NIT-based trial can prove effects on disease. Louise cautions that operator competency is a key, if overlooked, criterion for this kind of activity. Sven concurs and states that repeat measures are crucial in managing disease. Jörn notes that practices can serve as centers of care, but will need support from nutritionists and other professionals.
01:06:08 - Business Report
Roger highlights special September programming, indicates that new sponsors are on the way, an
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00:00:00 Surf's Up, Season 6, Episode 6.
On April 23, 2024, our colleague and co-founder, Stephen Harrison, passed away suddenly. This week, Surfing the MASH Tsunami remembers Stephen with two of his closest associates and continues our annual MASH Drug Development roundtable held in his honor.
00:00:04:24 - A Deep Dive into Drug Development, Part 2
The second portion of the Drug Development roundtable primarily focuses on three key issues. The first, uptake of resmetirom, starts with Naim Alkhouri discussing his experience in the Arizona Liver Health Clinics with over 650 patients in the year since resmetirom was approved and shifts to the various European panelists (Jörn Schattenberg, Louise Campbell and Sven Francque) estimating when it might be approved in their countries and how widely it might be reimbursed. The second topic, incretin agonists, focuses on exciting prospects for other incretin agonists in development, as well as some semaglutide combination therapies. The third, NIT clinical trials, covers prospects that non-biopsy clinical trials might be approved sometime in the near future.
00:16:20 - Remembering Stephen Harrison I: An Interview with Summit Clinical Research CEO Gail Hinkson
Summit CEO Gail Hinkson joins Roger Green for the first time on SurfingMASH to discuss her business partner. Gail discusses how the two originally formed Pinnacle Clinical Research and how Pinnacle led to Summit. She proceeds to discuss the current size and reach of both Pinnacle and Summit. Focusing on Summit, Gail describes the company as an Integrated Research Organization (IRO), highlighting its distinct role within the MASH firmament. In the final section of the interview, Gail discusses how Stephen's personality, goals, and vision continue to live on at Summit today.
00:34:31 - Remembering Stephen Harrison II: An Interview with Naim Alkhouri Announcing That He Is Joining Summit
Newly announced Summit Chief Academic Officer Naim Alkhouri joins this episode for a second time, but in a very different role. Naim discusses his personal history with Stephen and what he loved and respected about his "dear friend." He then makes a major announcement: he is joining Summit as Chief Academic Officer. He shares the many elements of this role, particularly his excitement that Summit can become the entity that educates a wide range of healthcare and commercial professionals on what MASH is and how it is treated. The scope of this vision, combined with what Gail discussed, portrays a level of energy, ambition and vision worthy of Stephen Harrison.
00:55:55 - Conclusion
As part of this memorial week, Roger Green forgoes the usual business report, which will return next week.
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This week’s expert, Hepatologist and Key Opinion Leader Scott Friedman, joins Roger to discuss advances in acceptance of gene therapy and knowledge in other areas of basic liver science. When discussing science, he pays particular attention to findings on the diversity of stellate cells and his interest in CAR-T as a therapy for liver disease.
This conversation starts with Scott discussing gene therapy. Specifically, he applauds the idea that gene therapy is becoming accepted in many diseases after a faulty start years ago, due to an unfortunate patient death in a badly controlled trial. He comments that this acceptance has unique benefits in liver disease because the liver can regenerate so much faster and more efficiently than other organs. He mentions some of the rare liver diseases in which patients are benefiting from gene therapy, and notes that we now have gene therapies and early-stage trials to target PNPLA3 and other genes associated with MASH and MASH cirrhosis.
Next, Scott discusses stellate cells, which he has discussed in earlier episodes of SurfingMASH. Science is increasingly demonstrating how many different types of heterogeneous stellate cells exist. As Scott puts it, these cells "come in many flavors," each of which plays a different role in cell generation or cell death. In fact, the specific therapeutic challenges that present themselves may vary as a patient moves along the pathway from F1 to F2 to F3 to F4. Further, we are learning that there may be several different forms of MASH to present differently at a cellular level. This makes tremendous sense, given that no one drug has proven successful in even a significant majority of patients yet.
As the conversation winds down, Scott shares what he describes as a "sobering note" about the state of research funding in America in 2025. As he notes, there are certain kinds of applied and developmental research that private companies do well, but other kinds of basic research that only occur when funded in public and not-for-profit sectors. As a specific example, he cites CRISPR, initially funded publicly and now in the hands of biotech companies, which is used to treat a variety of diseases more effectively than they could have been treated before, if at all. He also comments that a poor early commercial decision slowed the development of statins.
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This weekend’s Newsmaker, Indiana University hepatologist and key opinion leader Naga Chalasani, joins Roger Green to discuss Early Experience with Resmetirom To Treat Metabolic-Associated Steatohepatitis with Fibrosis in a Real-World Setting, an article his group published recently in Hepatology Communications. He shares highlights from the paper and points out the one key area in which his group found room for improvement in their initial protocol.
Naga and colleagues wrote this paper after learning from Madrigal Pharmaceuticals that they were among the largest early prescribers of resmetirom and, relative to others, had achieved reimbursement with virtually all their patients and a high percentage of patients actually starting the medication. After receiving requests from other states for advice, the group decided to author this paper.
In the paper, Naga and colleagues focused on patient selection, care pathway, how IUHealth got the medicine to their patients, and experience with safety and tolerability.
In the paper, Naga and colleagues discuss their experiences in prescribing resmetirom for 113 patients in the first seven months after resmetirom's approval. Of these, IUHealth succeeded in achieving reimbursement for 110 of them. Of these patients, 83 initiated therapy, and 16% of those discontinued.
In this interview, Naga shares some of the decisions that made the group so successful in the first three areas and identifies one subsequent area where the group found an opportunity for improvement: systematic follow-up with patients after prescribing. He attributes the 16% discontinuation rate to a "prescribe and forget" policy, similar to one that was successful in HCV, where clinicians prescribed without systematic follow-up until blood levels were obtained three months later. With a "prescribe and follow up" policy that includes phone calls at 1 and 3 months, he anticipates discontinuation rates will fall to something akin to the 5% rate in Phase 3 trials.
What makes this interview so fascinating is Naga's description of the thinking that went behind specific decisions the group made in terms of patient management and pathway and suggests other options that might work as well. In all, this interview provides an excellent guide for clinics and providers on how to best integrate resmetirom into their practices.
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This conversation is the opening segment of SurfingMASH's April discussion, in memory of Stephen A. Harrison, on drug development. In addition to co-hosts Jörn Schattenberg, Louise Campbell and Roger Green, panelists include hepatologists and key opinion leaders Sven Francque and Naim Alkhouri. This opening discussion focuses on exciting advances in one drug class (FGF-21s) and, more broadly, on exploring ways to treat cirrhosis.
As Naim points out in his opening comment, these two issues— cirrhosis as a challenge and FGF-21s as a possible solution path —intersect in clear and exciting ways. He notes that the FGF-21 efruxifermin has been reported to have significant improvement in patients with cirrhosis, while the FGF-21 pegozafermin has shared positive results in a small cohort of patients. He also notes that a third FGF-21, efimosfermin alfa, has results in advanced non-cirrhotic MASH that suggest potential for similar efficacy in patients with cirrhosis, but this must be studied and confirmed in clinical trials. He mentions that resmetirom may also be showing signs of efficacy in some patients with cirrhosis. The entire package, he says, is a "game changer."
Jörn notes that we are having parallel advances in treatment for advanced, non-cirrhotic patients. Sven concurs and comments that we are seeing effects that are not strictly related to metabolic disease. There is exceptional power that we can demonstrate one-level regression in sicker patients.
The three agree that, at the same time, we are seeing cirrhosis trials that will lead to outcomes data; outcomes trials in non-cirrhotic medications may not be far away.
Roger asks whether we are making progress in treating patients living with decompensated cirrhosis. Sven discusses what we are learning about treating portal hypertension, which is an important benefit unrelated to fibrosis regression. Simply improving portal hypertension will have an impact on endpoints. Naim points out that some ongoing trials include patients with cirrhosis, including survodutide and belapectin.
Louise notes it will require "great P.R." to reverse some of the current perceptions about cirrhosis, but that this is "great." Naim states that even today, we have "a lot to offer" patients with portal hypertension or other symptoms of decompensation. As he concludes, he notes that this is underappreciated today.
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00:00:00 - Surf's Up: Season 6 Episode 5
Host Roger Green briefly describes this episode’s three sections and introduces Roundtable guests. The Roundtable panel shares groundbreakers.
00:10:39 - Roundtable: A Deep Dive Into Drug Development, Part One
The opening portion of this month's roundtable centers around two issues: exciting data for FGF-21s and, more generally, treating patients with cirrhosis. Naim Alkhouri sets the tone in his opening comments, which start by focusing on the exciting SYMMETRY data from efruxifermin and then hones in on FGF-21s and resmetirom in cirrhosis. The rest of the conversation features Jörn Schattenberg, Sven Francque and Naim discussing therapies in development for compensated and decompensating cirrhosis.
00;24:44 - Newsmaker: Naga Chalasani on Real-World Experience Prescribing Resmetirom
Naga joins Roger to discuss the paper Early Experience with resmetirom to treat Metabolic Dysfunction-Associated Steatohepatitis With Fibrosis in a Real-World Setting from his group at Indiana University, which his group authored and Hepatology Communications recently posted. The paper, based on IU Health's experience with its first 113 resmetirom patients, shares the group's practical experience developing processes to work closely with the specialty pharmacies dispensing resmetirom and, finally, concludes that a more engaged patient management strategy might reduce drug discontinuation to a level comparable with clinical trials.
00:47:21 - Expert: Scott Friedman on Gene Therapy, Diversity of Stellate Cell Types, Other Basic Liver Science
Scott and Roger cover a range of basis science topics in a fast-moving 19-minute discussion. It starts with Scott discussing the increasing acceptance that gene therapy is an acceptable way to treat a range of liver diseases, many of which are orphan or ultra-orphan but, in fact, include potential gene therapies for non-cirrhotic MASH and MASH cirrhosis. He notes that in addition to classic gene therapy, which introduces protective gene variants into the systems of patients with the risky variants, gene therapy is now looking to introduce FGF-21 into patients through genetic modification. From there, the conversation covers CAR-T therapy, the increasing ability to identify many different types of stellate cells and the idea that the most effective therapy for eary fibrosis, advanced fibrosis and cirrhosis might require fundamentally different kinds of interventions. The two final elements are the idea that what we now call "MASH" may be several diseases with different etiologies with similar manifestations and a passionate call for all of us to support maintaining NIH funding in whatever ways we can.
01:06:45 - Business Report
As Roger copes with his laryngitis, AI voices deliver an abbreviated business report
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This week's expert, Hepatologist and Key Opinion Leader Mazen Noureddin, joins Roger to discuss major advances in drug development over the past year. He covers a range of different drug classes, focusing on stages of development and the range of options within each class.
First, Mazen discusses a tremendously exciting group of FGF-21 agents, specifically mentioning Akero Therapeutics's efruxifermin, 89bio's pegozafermin, and Boston Pharmaceuticals's efimosfermin. He points to efruxifermin’s 96-week results to suggest that FGF-21s might be appropriate for a wide range of patients, the idea that the drug's duration of effect may make the idea of “induction therapy” less appropriate, and the exciting early data on cirrhosis patients. He also mentions pegozafermin's publication of data in the New England Journal of Medicine and efimosfermin's promising data based on monthly dosing.
Next, Mazen provides some detail on the various incretin agonist options, why hepatologists are particularly excited about combinations that include a glucagon agent, and what kinds of results we might expect in upcoming trials.
Finally, Mazen discusses other promising compounds in later-stage development, including the pan-PPAR lanifibranor and the FASN inhibitor denifenstat. He notes ongoing work on new classes and combination therapies.
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This weekend's Newsmaker, Fatty Liver Alliance Founder Mike Betel, joins Roger Green to discuss the wide range of conferences where he has been invited to speak or sit on a panel this year. Specifically, he shares his belief on what this says about interest in MASLD and describes the messages he delivers at the conferences he attends.
The interview starts with Roger asking about the benefits societies and the broader community get from having Mike at these programs. As he puts it, "I feel quite fortunate that I get to be, as you've shared before, the one sitting in the front row center, paying very close attention to every word that the speakers are saying so that I can share it back as it's happening." The posts he sends back from these meetings are well-received, with many reaching a 30% engagement rate and some exceeding 50%.
He has been struck by the breadth of the organizations seeking to learn more about the liver and MASLD. The conference that struck him most in the last six months was the American Diabetes Association meeting, where only two MASLD KOLs spoke. Still, there was tremendous interest in MASLD throughout the conference. His key takeaway from the new conferences he attends, many of which are about diabetes or obesity, is how important it is for physicians to be sensitive in the language they use and, generally, the level of interest/empathy they show their patients. He believes this will be particularly important for front-line treaters, many of whom must fit this new, more open approach into an 8-minute visit.
Mike's most important message is about "tailored therapy," therapeutic approaches sensitive not only to the patient's disease but also their life circumstances. An example he gives: taking 10,000 steps per day may not be feasible for a person living with obesity who is starting therapy, so why make that number the goal?
Mike's final message to patients is to ask lots of questions, particularly about the comorbidities or test results that might suggest potential for future problems.
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This conversation is the concluding segment of SurfingMASH's coverage of the AASLD Emerging Trends Conference on the SLD Spectrum diseases: MASLD, MetALD and ALD. In addition to co-hosts Louise Campbell and Roger Green, panelists include EASL Secretary General Aleksander Krag, hepatologist Alex Lalos and Jenn Leigh Jones, Founder of the Society for Sober Livers Survival patient advocacy group.
The conversation starts with Roger questioning whether it is a good or bad idea to conduct separate studies on medicines' effect on MetALD patients. He notes Anna-Mae Diehl's presentation at the Conference, which suggested that regardless of organ, all cell senescence and death results from iron overload, and asks whether we should be studying this phenomenon. Aleksander agrees that important questions around iron exist and should be addressed in future research. He places this issue in context by noting that after decades of failed drug trials, SLD research has produced a string of exciting successes using different modes of action.
The group turns to discuss cirrhosis, based on recent presentations from Akero Therapeutics for its agent efruxifermin. Alex notes that his quick read of slides revealed that some of the cirrhosis patients had fairly advanced disease. He expresses a high level of enthusiasm that the prospective MASLD therapies discussed in this meeting will be the third major advance during his career in medicine.
Roger asks the group two closing questions: one lesson each panelist is taking from the meeting and one message they would like to share with listeners. The group members all land in a similar place: there is a spectrum running from MASLD through MetALD to ALD and we are learning how their commonalities and differences are the keys to developing better treatments and guidelines.
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00:00:00 - Surf's Up: Season 6 Episode 4
Surfing the MASH Tsunami concludes its coverage of the AASLD Emerging Trends Conference on MASLD, MetALD and ALD. This week, the panelists focus on pivotal messages that attendees took away from the conference and what messages they would like to share with listeners. Our newsmaker, Fatty Liver Alliance and CEO Mike Betel, discusses the lessons he has taken from being invited to a far wider swath of conferences this year and shares the messages he delivers to these new audiences. Finally, our expert, hepatology research and key opinion leader Mazen Noureddin, discusses recent advances in drug development, focusing on agents in Phase 3 trials.
00:04:24 - Introduction
Host Roger Green briefly describes this episode's three sections and one key lesson from each.
00:06:03 - Roundtable: Highlights from the AASLD Emerging Trends Conference, Part 4
This is the concluding portion of our Emerging Trends Conference Roundtable. The group focuses on key lessons they have learned and messages they would like listeners to take from this conversation. The pivotal idea is that SLD is a spectrum running from MASLD through MetALD to ALD. Researchers and treaters will all do best in developing and implementing therapies and guidelines with this thought in mind. Aleksander Krag stresses this idea and notes that, with several different classes of drugs demonstrating positive impact, it will be an exciting decade ahead as we learn how to apply these drugs along the spectrum. Jenn Jones and Alex Lalos note the importance of identifying MetALD, although Jenn noted that it does not seem wise to conduct trials solely with MetALD patients at this time.
00:22:04 - Newsmaker: Mike Betel on the Increased Visibility of Patient Advocates
This week's newsmaker, Mike Betel, has experienced a significant increase in the number of conferences at which he is invited to speak or appear on a panel. This discussion centers around the reasons Mike believes this is happening and the message(s) he delivers. To Mike, his most important contribution lies in the amount of information he sends back from each event, many of which surpass 30% download rates (and some even hit 50%). He discusses his value in diabetes, endocrinology and obesity meetings, where he brings a "liver" perspective and co-education opportunity to these events. The entire experience has taught him about the need not to stigmatize patients and reinforced his belief in the importance of tailoring care to patients' needs and personalities.
00:49:28 - Expert: Mazen Noureddin on the Exciting MASLD Drug Development Environment
Hepatologist and Key Opinion Leader Mazen Noureddin joins Roger to discuss major advances in drug development over the past year. He covers a range of different drug classes, focusing on stages of development and the range of options within each class. Specifically, he discusses the FGF-21 agents, the range of patients for whom they might be appropriate, how efruxifermin's 96-week results may make the idea of "induction therapy" less appropriate, and the exciting early data on cirrhosis patients. He provides some detail on the various incretin agonist options, why hepatologists are particularly excited about combinations that include a glucagon agent, and what kinds of results we might expect in upcoming trials. He goes on to discuss the pan-PPAR lanifibranor, the FASN inhibitor denifenstat, and notes ongoing work on new classes and combination therapies. In general, he paints, I think, not a rosy, but an extremely optimistic picture of what the future will be for patients who need to be treated for fatty liver.
01:09:38 - Business Report
Roger discusses the next Roundtable and provides some details on SurfingMASH's coverage of the upcoming EASL
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This week's Expert is Jeff McIntyre, Vice President, Liver Programs at the Global Liver Institute. His major topic is how recent high-level FDA job cuts might affect MASH drug and diagnostics development. He also shares reactions to FibroSIGHT, HistoIndex's new digital pathology service for clinical practice.
Highlight: Recent job cuts at the FDA will produce chaos in government and slow response to any emerging crises.
Second Highlight: Patient self-advocacy becomes even more important in this environment.
The conversation takes place on April 1, which lends context to Jeff's opening comment about the rate and nature of change in Washington, DC. He and Roger quickly focus on high-level job cuts at the FDA.
Jeff believes that the clearest outcome from these changes is that the government will be less able to respond promptly and in a medically appropriate manner to future health crises. Jeff agrees with former FDA Commissioner Rob Califf's comment that the FDA as we know it "is dead," and that we have little idea what the future holds.
A slower-moving, more chaotic government with a Secretary of HHS who minimizes pharmacotherapies for alternative therapies presents a challenge for all SLD patients. Jeff states that patients need to become more vigilant self-advocates (even more than they are today). He also identifies patient advocacy organizations like GLI as a place patients can go to seek the guidance and support they need from patient advocates.
Finally, the conversation turns to discuss FibroSIGHT. Jeff describes FibroSIGHT as "exactly where we should be and should not be at the same time," a technology that takes a significant step forward in understanding and patient support, but one that ties us to biopsy as a standard for clinical care. Jeff and Roger agree this issue will play out over the coming years.
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This week's newsmaker, Yukti Choudhury, Director of Clinical Development at HistoIndex, joins Roger Green to discuss FibroSIGHT, a new HistoIndex service that allows clinicians to use HistoIndex's Second Harmonic Generation (SHG) technology and analytics to determine specific CRN fibrosis level for patients with inconclusive NIT results.
One reason FibroSIGHT is worthy of attention: This is the first time an in-depth analysis of clinical trial biopsy results is being placed at the service of clinical treatment.
Another reason: Yukti states that demand for this technique could equal 163,000 cases this year, rising to one million by 2028.
The interview starts with Yukti sharing information on her own academic and commercial background and how she came to this role. She describes FibroSIGHT, a service that will provide a highly accurate CRN fibrosis level for patients whose NIT results suggest no clear or consistent finding.
Yukti provides practical cues on ordering the test and its reimbursement.
Roger shares his long-standing respect for SHG and the clarity it produces. He notes the economic benefit of determining whether a patient has F2 fibrosis, which is indicated for pharmacotherapy, vs.F1, which is not indicated. He sees clear benefit in this analysis.
Roger goes on to express concern that any option requiring more biopsies will reduce the number of patients treated, particularly if having this tool encourages payers to require a biopsy as a prerequisite to treatment. He asks whether, over time, HistoIndex might be able to develop a companion analytic to improve these estimates without requiring biopsy.
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Surfing the MASH Tsunami continues its coverage of the AASLD Emerging Trends Conference on MASLD, MetALD and ALD.
This week, the panelists focus on what studies on bariatric surgery and drugs in development can tell us about future treatment and explore some clinical trial questions. Guest Surfers include Professor Aleksander Krag of the University of Southern Denmark, the current Secretary-General of EALS, hepatologist Alexander Lalos of Robert Wood Johnson hospital, and Jenn Leigh Jones, founder of the Society for Sober Livers Survival, now part of the Fatty Liver Foundation.
Aleksander Krag starts by discussing a presentation on what we can learn from bariatric surgery in terms of fibrosis reduction and why pharmacotherapies work (or not). He envisions a day where we have multiple treatment options and understanding how each works for specific types of patients, leading to robust, cost-effective, patient-specific treatment algorithms.
Alex Lalos describes how presentations on FGF-21s in advanced fibrosis and cirrhosis have whetted his appetite and Jenn Jones asks questions regarding ALD patient trial selection and assignment and clinical endpoints for cirrhosis trials.
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00:00:00 - Surf's Up: Season 6 Episode 3
Surfing the MASH Tsunami continues its coverage of the AASLD Emerging Trends Conference on MASLD, MetALD and ALD. This week, the panelists focus on what studies on bariatric surgery and drugs in development can tell us about future treatment and explore some clinical trial questions. Our newsmaker, HistoIndex Director of Clinical Development Yukti Choudhury, introduces us to FibroSIGHT, which provides clinicians with highly precise biopsy analysis. Finally, our expert, Global Liver Institute Vice President, Liver Programs Jeff McIntyre, discusses the implications of recent US government job cuts on future MASH treatment options and patient care.
00:04:35 - Introduction
Host Roger Green briefly describes this episode's three sections and one key lesson from each.
00:05:45 - Roundtable: Highlights from the AASLD Emerging Trends Conference, Part 3
This portion of our Emerging Trends Conference Roundtable looks at how therapy might evolve over time. Aleksander Krag starts by discussing a presentation on what we can learn from bariatric surgery in terms of fibrosis reduction and why pharmacotherapies work (or not). He envisions a day where we have multiple treatment options and understanding how each works for specific types of patients, leading to robust, cost-effective, patient-specific treatment algorithms.
Alex Lalos describes how presentations on FGF-21s in advanced fibrosis and cirrhosis have whetted his appetite and Jenn Jones asks questions regarding ALD patient trial selection and assignment and clinical endpoints for cirrhosis trials.
00:16:55 - Newsmakers: FibroSIGHT Brings Clinical Trial Analytics to Clinical Practice Use of Biopsy
Yukti Choudhury, Director of Clinical Development at HistoIndex, joins Roger Green to discuss FibroSIGHT, a new HistoIndex service that allows clinicians to use HistoIndex's Second Harmonic Generation (SHG) technology to determine specific CRN fibrosis level for patients with inconclusive NIT results. Yukti states that demand for this technique could equal 163,000 cases this year and rising to one million by 2028. She provides practical cues on ordering the test and its reimbursement.
Roger shares his long-standing respect for SHG and the clarity it produces. He notes the economic benefit of determining whether a patient has F2 fibrosis, which is indicated for pharmacotherapy, vs.F1, which is not indicated. He sees clear benefit, but expresses concern that any option requiring more biopsies will reduce the number of patients treated.
00:41:49 - Patient Advocate and Policy Expert Jeff McIntyre Discusses the Implications of FA/NIH Job Cuts on MASLD Patient Care
Global Liver Institute Vice President, Liver Programs Jeff McIntyre joins Roger to discuss the April 1 job reductions at the FDA, explore implications for the entire MASLD community, and to ask what patients can and should do. Jeff and Roger note that the job changes will create significant uncertainty and probably reduce the government's ability to respond to future health crises. Jeff notes former FDA Commissioner Rob Califf's comment that the FDA as we know it "is dead," and that we have little idea what the future holds. According to Jeff, patients need to become even more vigilant self-advocates and also seek the guidance and support they need from patient advocacies.
Finally, the conversation turns to discuss FibroSIGHT. Jeff describes FibroSIGHT as "exactly where we should be and should not be at the same time," a technology that takes a large step forward in understanding and patient support, but one that ties us to biopsy as a standard for clinical care. Jeff and Roger agree this issue will play out over the coming years.
01:09:18 - Business Report
Roger thanks listeners quotin
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00:00:00 - Surf's Up: Season 6 Episode 2
Surfing the MASH Tsunami continues its coverage of the AASLD Emerging Trends Conference on MASLD, MetALD and ALD. This week, the panelists focus on disease epidemiology and what it can teach us about the relative importance of alcohol and diet on disease progression. Our newsmaker, hepatology KOL and frequent Surfer Hannes Hagstrom, discusses what a recent paper demonstrates about the impact of MASLD on 15-year mortality and cause of death and how this information can improve patient care. Finally, our Expert, Shelbyville, Indiana internist Emily Ann Andeya, discusses her path from practicing internal medicine to focus on liver health (HINT: the common theme is insulin resistance).
00:04:40 - Introduction
Host Roger Green briefly describes this episode's three sections and one key lesson from each.
00:05:49 - Roundtable: Highlights from the AASLD Emerging Trends Conference, Part 2
The second portion of our Roundtable focuses on relative impact of alcohol and diet on disease progression and overall mortality and morbidity. It starts with Aleksander Krag sharing the highlights of his epidemiology presentation at the Emerging Trends Conference. Dr. Krag points out that while the vast majority of SLD patient live with MASLD, the vast majority of hospitalized patients and those living with late-stage cirrhosis live with ALD. Similarly, for the average patient, living with MetALD is more lethal than living with MASLD. Aleksander points out another challenge in defining where a patient lives on the ALD -> MetALD -> MASLD spectrum: patients' level of alcohol consumption is likely to change over time and many ALD or MetALD cirrhosis patients stop drinking altogether. The rest of this section considers the importance of stigma in correctly classifying patients and why genetics may become key to a message that minimizes patient stigma.
00:25:50 - Newsmaker: Hepatology Researcher and KOL Hannes Hagstrom of the Karolinska Institute joins Roger to discuss cause-specific mortality in Swedish MASLD patients
On March 24, the Journal of Hepatology posted a paper titled Cause-specific mortality in 13,099 patients with metabolic dysfunction-associated steatotic liver disease in Sweden. Co-author Hannes Hagstrom joins Roger to discuss the paper's key findings and implications for care. The key finding: living with MASLD leads to a significant increase in 15-year mortality. The most frequent cause of death among MASLD patients is cardiovascular disease, but the greatest increases in relative risk were due to HCC (HR ~ 35) and extra-hepatic cancers (HR ~ 26). Hannes points out that these results can serve as the beginning of a process where physicians can compute the risk at which individual patients place themselves through diet or alcohol patterns, which can aid patient understanding of the disease.
00:44:22 - Experts: Internist Emily Ann Andeya discusses how she developed the commitment to treating liver disease that made her a "unicorn" in the words of one AASLD panelist and also brought her to attend the Emerging Trends Conference last month
Roger first met Emily Ann Andeya when she asked a question at a session of last fall's The Liver Meeting, and again at the Emerging Trends Conference, where Emily and her colleagues were likely the only primary care physicians in the room. Emily describes the path by which she went from wanting to be a cardiologist during medical school in the Philippines through years of nursing in the US to primary care practice and, how, focus on the liver as a key to overall metabolic health. Listen as Emily explains the importance of understanding insulin resistance in her transition, and how her vision affects the way she and her colleagues practice, the goals they set, and
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00:00:00 - Surf's Up! Season 6 Episode 1
SurfingMASH kicks off our sixth season in our new format, with three major elements to each episode. This week's Roundtable and Newsmakers segments focused on two recent conferences that took a multispecialty perspective on the range of medical and psychological issues affecting steatotic liver disease (a new concept specialty: steatology.") Our Expert this week is our co-host Jörn Schattenberg, discussing the educational and conceptual challenges of readying Europe for the EMA approval of resmetirom later this year.
00:03:58 - Introductions and Groundbreakers
Host Roger Green describes the new v2.0 format. He introduces the guests for this month's Roundtable discussion of the AASLD Emerging Trends conference: co-host Louise Campbell, hepatology KOL and EASL Secretary-General Aleksander Krag, Alcohol Use Disorder and Alcohol Liver Disease patient advocate and Sober Livers patient support organization co-founder Jenn Leigh Jones, and clinical hepatology Alexander Lalos.
00:15:46 - Roundtable: Highlights from the AASLD Emerging Trends Conference, Part 1
The first portion of our Roundtable focuses on the emerging recognition throughout hepatology that MASLD, MetALD and ALD are best described as a disease spectrum, rather than discreet diseases. This has implications for the medical specialties involved in treatment and the entire way we look at this diseases.
00:32:35 - Newsmakers: Arizona Liver Health Institute Chief Medical Officer Naim Alkhouri and Fatty Liver Alliance Founder Mike Betel Discuss the 2025 Deser Liver Conference
Now in its fourth year, the Arizona Liver Health Institute's Desert Liver Conference has become a major multispecialty event on the Winter conference agenda. Arizona Liver Health Chief Medical Officer and hepatology KOL Naim Akhouri and patient advocate and Fatty Liver Alliance Founder Mike Betel join Roger Green to discuss the conference, including what makes it unique. Listen to Naim introduce a new description of the science of SLD.
00:55:21 - Experts: SurfingMASH co-host and hepatology KOL Jörn Schattenberg joins Roger Green to discuss how Europe is preparing for the launch of resmetirom and his own focus on this issue
Our third co-host, Jörn Schattenberg, could not join the February roundtable discussion. Here, he joins Roger to update listeners on his activities over the past six months. Most of the discussion centers around the necessary steps for Europe to prepare for the launch of resmetirom (anticipated to occur later this year), particularly given that the overall environment is more "siloed."
01:11;15 - Wrap-up: Roger presents "the shortest Business Report ever"
Roger discusses one continuing feature of Business Reports in the future from today and leaves all his other topics for next week.
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In this episode, Naim Alkhouri, Mike Betel, Michelle Long and Jeff McIntyre join Jörn Schattenberg and Roger Green to look back at The Liver Meeting 2024. This conversation reviews two sessions promoting healthy livers and asks panelists what they anticipate for #TLM2025.
This last conversation starts with Jeff describing the session that moved him most and praising a panel that Mike co-chaired on Lifestyle Management of MASLD and MASH. Jeff spoke on this panel, and he describes the breadth and quality of speakers and topics. While Jeff spoke about social determinants of health, others discussed commercial, regulatory and lifestyle determinants, all intermixed with practical advice on managing patients' lifestyle issues. Finally, he comments on a presentation from Meena Bansal discussing several concurrent posters in the meeting that aligned with the discussion in the session.
After Jeff shares the content of the meeting, he comments on the large number of providers and industry executives who attended this patient-centered session. Roger notes a similar distribution of attendees at the Health Livers, Healthy Lives session on building momentum for prevention.
In wrapping up the session, Roger does not share another presentation but notes how many modes of action have produced successful Phase 2/3 trial results. He notes that we may have 4-5 different modes of action available five years from now.
In the rest of the session, panelists describe what they believe will be different and exciting at #TLM2025. Answers vary, but most focus on advances in drug development and/or NITs.
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In this episode, Naim Alkhouri, Mike Betel, Michelle Long and Jeff McIntyre join Jörn Schattenberg and Roger Green to look back at The Liver Meeting 2024. This conversation considers the role of patient advocacy in replacing biopsy in clinical trials with NITs and reviews a session on the foundational principles for patien-centric clinical trials.
This conversation picks up at the end of Michelle's discussion of the FDA Corner session. Jeff starts by identifying this specific issue - replacing biopsy in clinical trials with NITs - as a place topic on which he believes patients must play a pivotal role in this discussion. He notes that patient advocacy has been involved already but anticipates this role will grow as the discussion progresses. After Michelle agrees how vital this issue is for patients and notes that manufacturers are
"taking on this increased workload" for that reason, Jeff shares what he considers the key issue: FDA is not only a scientific agency but also a political one, and patients can serve as the "tip of the spear" toward political ends here.
Mike describes a poster he presented (and was lead co-author), titled Patient Voice in MASH Initiatives: Foundational Principles for the Conduct of Patient-Centric MASH Research. He lists the groups participating in this broad effort and describes the goal as "reimagin[ing] clinical trials for MASH and how they're designed and delivered... focusing on what matters the most for patients." The outcomes were a set of patient-centric principles:
- Transparency in explaining trial-related issues. Mike gave the example of placebos, how they are used, and what happens to a patient in the placebo cohort at the end of the trial.
- "Whole person focus," including not only the medical issues but also emotional and practical issues that can emerge throughout the trial as patients' needs and life situations change.
- "Patients as partners," treating them as collaborators instead of subjects.
- Family and caregiver awareness, noting how deeply involved family members are through the trial process.
- Responsiveness to patient needs through surveys and checkpoints throughout the process.
Mike closed his comments by stating that all these points "put the patient at the center of the process," which meant considering not only diversity and inclusiveness in the trial population but also knowing and acting on what diversity will be in the context of these five principles.
Speaking from their perspectives as researchers, Michelle and Jörn were both highly supportive of the principles (Michelle called them "fantastic.") Jörn noted that the entire trial process starts with patient-centricity since the research is inherently designed to benefit patients.
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In this episode, Naim Alkhouri, Mike Betel, Michelle Long and Jeff McIntyre join Jörn Schattenberg and Roger Green to look back at The Liver Meeting 2024. This conversation reviews the late-breaker presentation on efimosermin, a q4w FGF-21 agent and the "FDA Corner" session.
Jörn begins the discussion by highlighting a paper from the later breaker session on efimosfermin alfa, an FGF-21 agent dosed q4w. He notes that after only six doses (24 weeks), efimosfermin alfa demonstrated significant increases in fibrosis regression and lowering NAS score. To Jörn, this result, coupled with others on efruxifermin and pegozafermin, suggest that FGF-21s are likely to play a significant role in MASH therapy once approved. After Roger and Mike note their enthusiasm about the drug class and this study, Jörn mentions a study with 96-week efruxifermin that data demonstrates prolonged efficacy. As he points out, this matters because while studies of an earlier FGF-21 candidate suggested that antibodies might develop in FGF-21 therapy, that does not appear to be an issue here.
Mike asks the group why they feel placebo performs so well in clinical trials. Jörn suggests that working with a compassionate clinical care team in dealing with the patient leads to better performance on diet and exercise and, as a result, increased placebo response to what we might find in general community practice.
Michelle praises the FDA Corner session, particularly the agency's transparency and willingness to engage industry and academia in finding paths to move away from biopsy. She also notes some of the practical challenges inherent of moving away from biopsy using data from earlier trials with an outmoded histology reader setup. She is optimistic about the scientific community coming together to address these issues. Jeff praises the agency for an "amazing" session.
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In this episode, Naim Alkhouri, Mike Betel, Michelle Long and Jeff McIntyre join Jörn Schattenberg and Roger Green to look back at The Liver Meeting 2024. This conversation considers how the anticipated approval of a second MASH drug without biopsy might affect clinical trials and discusses two recent publications on patient genotyping and patient clusters.
The conversation starts with Roger asking the group whether the presence of two approved MASH medications that do not require biopsy will make recruiting clinical trials that require them more challenging. The group doubts this will not add a significant new challenge to already-challenging trial recruitment. Naim comments that while this is a concern, it is already factored into trial schedules and that, given the number of patients available for trial, this should be highly manageable. Michelle discusses the importance of risk stratification in overall trial enrollment and this issue. Jeff and Mike agree that while this is a concern, it is part of a broader concern about the use of biopsy and should not in itself be a primary focus in terms of trial design at this point in time.
Naim introduces two other topics he considers worthy of consideration: the impact of synergy between resmetirom and GLP-1 agonists and the importance of different genetic polymorphisms in predicting the impact of drugs on specific patients. On synergy, he comments that MAESTRO-NASH data suggests that the presence of a GLP-1 does not affect the impact of resmetirom on fibrosis level. On the second point, he notes that several papers looked at major genotypes like PNPLA3 and HD17N13 and specifically cites a late-breaker from Arun Sanyal indicating that g-allele status may impact MASH independent of weight or insulin. Michelle mentions a recent paper in Nature identifying distinct clusters of patients based on how their SLDs progress over time, with a two-cluster solution indicating patients with concomitant diabetes and obesity vs. those without these two concomitant diseases. Roger shares a key point from each paper on treatment in the US. Data in the PNPLA3 paper might suggest that the course of disease in Hispanics, who have high levels of g-allele abnormalities, might be different from other ethnic groups with far lower abnormality rates. He also notes that the faster disease progression in the non-metabolic cluster highlights the importance of learning more about Lean MASH and how to treat it, since faster progression of disease suggests later diagnosis and higher morbidity, mortality and treatment costs levels.
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In this episode, Naim Alkhouri, Mike Betel, Michelle Long and Jeff McIntyre join Jörn Schattenberg and Roger Green to look back at The Liver Meeting 2024. This conversation reviews the ESSENCE trial, the Phase 3 trial demonstrating that semaglutide regresses fibrosis levels in some MASH patients.
The conversation begins with each panelist sharing a word or short phrase they felt best captured their feelings about TLM2024. Next, panelists review the meeting's most consequential paper, the ESSENCE Trial. Naim starts by describing ESSENCE, a Phase 3 trial with semaglutide demonstrating significant levels of fibrosis regression in non-cirrhotic MASH patients. Jörn adds the hopeful note that NITs performed as well as or better than biopsy in this trial, which he hopes will speed the transition in diagnostic approaches and tools. Jeff and Mike agree that from the patient's perspective, ESSENCE will be seen as a milestone in MASH therapy: the proof that a second drug can succeed in MASH. As the conversation ends, Roger notes that approval of a second agent for a particular disease often leads to dramatic growth in overall drug treatment by changing the pivotal question from whether to treat with a drug to which choice to prescribe.
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00:00:00 – Surf’s Up: Season 5 Episode 26 - Last month, close to 8,000 hepatology stakeholders convened in San Diego for The Liver Meeting 2024. Hepatology Key Opinion Leader Naim Alkhouri, Novo Nordisk International Vice President for Medicines Michelle Long, and patient advocates Jeff McIntyre from the Global Liver Institute and Michael Betel from the Fatty Liver Alliance join Jörn Schattenberg and Roger Green to discuss highlights.
00:03:23 - Introduction and Groundbreaker - Highlights include recent travel, cultural events, and the Third Annual Primary Care Summit from the Fatty Liver Alliance.
00:11:35 - Describing TLM2024 - Participants shared a word or short phrase they felt best captured their feelings about TLM2024.
00:14:51 - The ESSENCE Trial - Naim starts the session by describing ESSENCE, a Phase 3 trial of semaglutide in non-cirrhotic MASH patients, which he describes as "the most exciting news of the meeting." Panelists describe the benefits of this trial from a variety of perspectives.
00.22.49 - A Challenge to Trial Recruitment? - Roger asks the group whether the presence of two approved MASH medications that do not require biopsy will make recruiting clinical trials that require them more challenging. The group doubts this will not add a significant new challenge to already-challenging trial recruitment.
00:29:22 - Other keys in drug development - Naim begins a discussion of two topics: the value of synergy between resmetirom and the GLP-1 agonist, and the importance of different genetic polymorphisms in predicting the impact of drugs on specific patients. Michelle mentions a recent paper in Nature identifying distinct clusters of patients based on how their SLDs progress over time. Roger identifies two particular challenges in this area, one posed by Lean MASH and the other specific to Hispanics in the US.
00:34:42 - FGF 21s - Jörn highlights a paper from the later breaker session on efimosfermin alfa, an FGF-21 dosed q4w. Roger and Mike comment. To Jörn, this and other studies demonstrate the place FGF-21s are likely to have in MASH therapy.
00:40:29 - FDA Corner and the Role of Surrogates - Michelle praises the FDA Corner session, particularly the agency's transparency and willingness to engage industry and academia in finding paths to move away from biopsy. She is optimistic about the scientific community coming together to address these issues. Jeff notes the pivotal role he believes patients must play in this process.
00:48:33 - Patient Insights - Mike describes a poster he presented (and was lead co-author), titled Patient Voice in MASH Initiatives: Foundational Principles for the Conduct of Patient-Centric MASH Research. He lists the groups participating in this broad effort and the foundational principles that emerged. Michelle and Jörn share their thoughts on which principles have the greatest impact on them in clinical research. Jeff praises a panel that Mike co-chaired on Lifestyle Management of MASLD and MASH. He praises the breadth and quality of speakers and topics. He also comments on the large number of providers and industry executives who attended this patient-centered session. Roger notes a similar distribution of attendees at the Health Livers, Healthy Lives session on building momentum for prevention.
00:58:36 - Wrapping Up - Roger comments on the breadth of modes of action that have produced successful Phase 2/3 trial results. He notes that we may have 4-5 different modes of action available five years from now. In the rest of the session, panelists describe what they believe will be different and exciting at TLM2025.
01:06:01 - Question of the Week
Listeners and readers, What do you consider the most essent
Two weeks ago, the SurfingMASH Question of the Week asked, "What structural or educational changes do you anticipate will significantly improve Provider-Patient communication? Will these changes require more from the provider and more from the patient?" Today, S5 E23 panelists Mike Betel and José Willemse join Roger Green to review the three answers we received.
Of the three questions from audience members, one from a patient/patient advocate suggested greater honesty, better listening, and, if possible, either longer appointments or better care team engagement. The second, from another patient, discussed being more honest about the Quality of Life impact of immunological drugs, along with ways to manage these drugs better. The third, from a public health official in Argentina, discussed increasing the use of multidisciplinary teams to educate and empower individuals around healthy habits and lifestyles.
To Mike, these answers all convey the need for "tailored care," a care and engagement process suited to each patient's individual situation in terms of disease(s) and quality of life needs and issues. He also suggests that pharmaceutical companies help educate physicians on these issues while discussing the disease and use of their medicines.
José notes that it might not be possible to get more time for a visit, but the physician could improve the visit immensely by asking patients true open-ended questions about their feelings and concerns and then actively listening to their answers. She also suggests that physicians not act like they are time-compressed. If physicians act more leisurely, patients will be more comfortable, even if they do not take up more time.
Roger suggests that the format of physician protocols and instructions might be part of the problem. If the physicians are evaluated by their employers based on their ability to work through an entire checklist in 15 minutes, they will focus first on the clock and second on the checklist. This will not leave time for patient questions and, even worse, will leave the patient afraid to take up any more of the physician's time than is necessary. Thus no true communication develops.
Mike goes back to a point that José made during the original episode: physicians should close their computer screens and look at the patients. Roger goes back to the question about immunosuppressants to ask whether providers can assess patients' abilities to manage medications that cause or exacerbate depression and then offer advice and perhaps antidepressants as appropriate.
Given all these emotive patient needs, José suggests that patient support groups have tremendous value, and Roger notes the presence of online support structures like HOPE from Sober Livers (Season 5 Episode 18). After asking where to find resources for these kinds of activities (particularly in less wealthy parts of the world), the conversation ends.
In the second half of Roger Green's interview with Global Liver Institute Vice President, Liver Programs Jeff McIntyre, Jeff discusses the implications of his key EASL Congress takeaways for GLI and other patient advocacy groups.
To Jeff, this trend makes patient advocates a more valuable player in the clinical trial design process, particularly when coupled with the FDA's increasing focus on diversity in trial populations. This will become particularly important because, today, the major use of incretin agonists like semaglutide and tirzepatide is in anti-obesity, where payers are frequently declining to pay for the drugs. Advocates like GLI will be pivotal in ensuring that patients who need MASLD drugs will still get the drugs they need, particularly at earlier stages of fibrosis. This discrimination may allow patients to receive incretin agonists during the pre-fibrosis stage based on diabetes and anti-obesity medications and reserve the fibrosis drugs for patients with more advanced MASH. The entire scenario of early metabolic, later MASH treatment with different agents is at least 4-5 years in the future. In the meantime, Jeff sees a need to advocate for underserved groups in the population while at the same time laying the foundation for the longer-term case. In this context, the United Nations General Assembly side effect (covered in S5, E22) is an exciting and vital event.
This conversation contains the first half of Roger Green's interview with Global Liver Institute Vice President, Liver Programs Jeff McIntyre, during which the two discuss what Jeff considered the key strategic takeaways for GLI from the various EASL Congress presentations, abstracts and discussions.
Jeff focuses on the "overriding sense of optimism" coming from the multiple pieces of positive drug data. He cites the data on Boehringer Ingelheim's survodutide, the follow-up work on Madrigal's resmetirom, an anticipated presentation on semaglutide at the AASLD in November, and strong FGF-21 results as proof that we are beginning to develop multiple robust, safe and effective modes of action for drugs to treat (at least pre-cirrhotic) MASH. His second positive point is that due to the drug trials and nomenclature change, GLI and other advocates are starting to have "more enlightened discussions" about MASLD in the context of the whole patient and related metabolic conditions. As a result, he comes to the third point, which is that multiple modes of action will teach us why what works in one patient might not in another and, ultimately, reshape clinical trials so that the target might not be fibrosis (or at least not only fibrosis), but instead exactly how each drug works. Jeff envisions this line of inquiry as a step down the path away from requiring biopsy.
In the second half of Roger Green's interview with PharmaNest Founder and CEO Mathieu Petitjean, Matt discusses the implications of his key EASL Congress takeaways for PharmaNest.
Matt starts this discussion with a simple question: Will biopsy-based analyses become part of a surrogate endpoint? As he points out, they are not today, and creating the necessary data might require a significant effort. If not, they are unlikely to remain relevant to the large, Phase 3 trials. Regardless of the answer to this question, Matt believes digital pathology will still be important in pre-clinical work and other efforts to define underlying liver structures and faults better. Also, he notes, digital pathology is valuable in an array of other liver diseases and in non-hepatological markets, notably including pathology. One way or another, he is confident PharmaNest will continue to make contributions to hepatology and grow as a business.
This conversation contains the first half of Roger Green's interview with PharmaNest Founder and CEO Mathieu Petitjean. After Matt tells the audience a little about his background and PhramaNest, the two discuss what Matt considered the key strategic takeaways for PharmaNest from the various EASL Congress presentations, abstracts and discussions.
Before answering the question, Matt describes the core services his company offers: "PharmaNest specializes in digital pathology. Four years ago, we put down the hypothesis that the histological phenotype of fibrosis should be quantified in a high-resolution, sophisticated way." He goes on to state their core proposition for MASLD: "The big idea here is that fibrosis equals phenotype." He proceeds to describe his offerings in greater detail before offering the underlying value of computed histology: fibrosis is a continuous variable that is scored in discrete categories under the NASH-CRN model that drives FDA analysis. With this as context, he answers the question by describing three kinds of MASLD clinical trial designs. The first, earliest trials had a single pathologist reading histological slides. The method is not precise, but the drugs were not very good, and none were ultimately approved. The second set of trials relied on more rigorous methods for pathologists to read histology slides, with multiple readers and robust adjudication systems. Also, the drugs in this second set of trials were more efficacious, so that NASH-CRN, while a blunt instrument, could adequately assess efficacy. For the third set of trials, Matt believes non-invasive tests (NITs) are likely to suffice.
00:00:00 - Surf's Up: Season 5 Episode 24
This week's episode on MASLD lessons from the EASL Congress 2024 includes three separate elements: individual interviews with PharmaNext Founder and CEO Mathieu Petitjean and Global Liver Institute Vice President of Liver Programs Jeff McIntyre, followed by a discussion with patient advocates Mike Betel of the Fatty Liver Alliance and José Willemse from the Netherlands, now supporting EASL.
00:02:45 - Introduction
Roger explains the episode format, including the two key questions for Mathieu and Jeff: (i) what were their key takeaways from the EASL Congress, and (ii) how have those takeaways changed how they do their jobs or plan for the future? Roger also sets up the Question of the Week discussion that is today's third section.
00:04:04 - Meet Mathieu Petitjean
This is the SurfingMASH debut for Mathieu Petitjean, Founder and CEO of PharmaNest. He tells the audience a bit about his background and his love of Harleys.
00:07:10 - First question to Matt
Matt begins by describing the core services Pharmest, a digital pathology company, offers MASH drug developers. Then he answers Roger's question by describing three phases in MASLD clinical trial designs. His point is that over time, drugs have gotten better, and histology requirements have become more onerous. At some point in the not-too-distant future, Matt believes non-invasive tests (NITs) are likely to suffice in large Phase 3 trials of the future.
00:21:01 - Second question to Matt
Matt starts the answer with a conditional: if biopsy-based analyses become part of a surrogate endpoint, the role is large and clear. If not, they are unlikely to remain relevant in Phase 3 trials. Regardless of the answer to this question, Matt believes digital pathology will remain important in pre-clinical work and in other continuous liver diseases with less-defined targets. Also, he says, digital pathology is valuable in an array of non-hepatological markets, notably including pathology.
00:29:11 - First question to Jeff
Jeff describes an "overriding sense of optimism" he felt due to the many positive drug trials presented in Milano. This suggests that the MASLD community is developing safe and effective MASH drugs with many different modes of action. This is allowing GLI and other advocates to start to have "more enlightened discussions" about MASLD in the context of the patient's overall metabolic state. All this means that what works in one patient might not in another. This can reshape clinical trials so that the endpoint target might not be change in fibrosis but impact against specific NIT targets. Jeff envisions this line of inquiry as a possible step away from biopsy.
00:39:34 - Second question to Jeff
Concurrently, FDA is beginning to require greater diversity in clinical trial populations. To Jeff, all this makes patient advocates like GLI more valuable to the clinical trial design process and pivotal in ensuring that metabolic and advanced MASH patients will still get the drugs they need. Starting today, Jeff sees advocates as championing underserved groups in the population while at the same time laying the foundation for the longer-term case.
00:55:20 - Discussing previous "Question of the Week"
This is a 15-minute discussion of the Question of the Week we posed at the end of S5 E23. This section will constitute S5 E24.5, which we will post in the next day or two. A more complete summary will appear there.
01:11:23 - Question of the Week
The Question of the Week is the first question Roger asks Matt and Jeff during this episode.
01:12:58 - Business Report
Previewing Episode 25, with Maru Rinella discussing the recently-published expert recommendations on use of resmetirom, along with comments on office hours the reason we will not have a vault conversation this week.
This week, Surfing the MASH Tsunami looks back on interviews Roger Green conducted during the EASL Congress itself. This conversation with SurfingMASH co-host and Tawazun Health Founder and Clinical Director Louise Campbell took place on the last day of the Congress.
This conversation centered on three major topics addressed at the EASL Congress, each of which made Louise "quite enthusiastic."
The first of these was the presentation of the new EASL/EASD/EASO Clinical Practice Guidelines and their practical implications (Season 5 Episode 21). Louise described this session as having "blown her mind" with its forward-thinking style and recommendations. She termed it a "leap of faith" that we all need to think differently about diabetes and obesity given how quickly incidence is growing. Her favorite items? The guidelines mentioned resmetirom even before it was approved in Europe. Also, the guidelines described ways to use several drugs that have not been approved for MASLD to treat patients with other metabolic conditions that are linked to MASLD. Louise also expressed enthusiasm at which three organizations partnered on this document.
Roger suggested that this aligned broadly with the various drug presentations in the Late Breaker and General sessions. Collectively, those presentations highlighted an array of drugs with different modes of action and strengths across the metabolic continuum. More generally, the two agreed that we are looking at a world where, in just a few years, we will have multiple drugs, most with unique modes and all with specific patient targets.
Roger asked whether Louise believes that over time, the diagnostic focus would stay with liver stiffness and CAP or switch to in-office PDFF. Louise suggested that in a world where clinical trials may not require biopsy, it would be difficult to build a sufficiently robust data set for any new tests.
This week, Surfing the MASH Tsunami looks back on interviews Roger Green conducted during the EASL Congress itself. This conversation with SurfingMASH co-host and Tawazun Health Founder and Clinical Director Louise Campbell took place on the first day of the Congress.
Roger's first interview with Louise took place at the end of Thursday, the opening day of the formal Congress and the first day of research presentations and posters. She starts by describing the "really nice vibe" of the meeting, dampened by the fact that Stephen Harrison was not there, and is no longer with us.
The first session Louise chose to discuss was the previous day's Patient Advocate session. To her, the key point was to learn a key question that every provider should share with every patient once a year. She mentioned briefly the one presentation from the day's General Session she was able to attend, a retrospective analysis of the predictive value of VCTE.
Next, Louise discussed two sessions she attended that delivered powerful, somewhat novel messages. The first was a symposium sponsored by Novo Nordisk that looked at using the liver "to manage cardiometabolic side" through the liver "rather than focusing on liver disease." The second was the "Healthy Livers, Healthy Lives" presentation that presented "very startling figures" about healthcare costs and lack of productivity in the US and how and why India has targeted this disease aggressively.
After Louise and Roger both commented on the building momentum in MASLD and mentioned why they believe this is happening, Louise noted how many conversations about AI and quicker population detection were occurring despite the lack of ability to act on these today. This let Roger recall his major takeaway from the Preview episode (S5 E17), which was the emerging importance of data development and large datasets. He mentioned a paper from the Karolinska Institute that Hannes Hagstrom discussed in that episode.
This week, Surfing the MASH Tsunami looks back on interviews Roger Green conducted during the EASL Congress itself. This conversation with Fatty Liver Alliance Founder and CEO Mike Betel took place Wednesday of Congress week, a day for special sections and industry presentations, but one day before the General Session opened.
The first part of the conversation centered on the Patient Advocate session that Mike chaired with Shira Zelber-Sagi. (This is the focus of Season 5 Episode 23.) The goal of this session was to discuss barriers to addressing unmet needs in a clinical setting and explore potential solutions. He listed the speakers and their topics, and then went straight to his key takeaway: patients around the world are having challenges getting personal attention and time from their treaters. He mentions one panelist who once told a doctor, "I know you're listening but you're not hearing me." The conversation also touched on stigma and how it comes into these discussions.
The rest of this interview touched briefly on the Opening Session and a couple of industry-sponsored sessions Mike attended. His final point was to emphasize the exceptional opportunities for networking at an event like this one.
This week’s vault comes from our first episode with Shira Zelber-Sagi. She and Ken Cusi joined us during US Thanksgiving Week 2022 to discuss nutrition and behavioral issues related to MASLD. The episode’s original writeup explains:
Surfing the MASH Tsunami hosts its first episode dedicated to nutrition and NASH with distinguished guest, Prof. Shira Zelber-Sagi. Alongside this rich discussion are Ken Cusi, Jörn Schattenberg, Louise Campbell and Roger Green.
This final conversation starts with Jörn recalling Shira's statement that “diet is every day.” He notes that for patients whose serious medical issues are related to poor diet and lifestyle choices, behavior and diet can play an integral role in improved patient self-care and overall health. Roger highlights that a combination of medications and self-management can be a powerful, reinforced and effective treatment solution. This leads Shira to provide a step-by-step vision of how to work with patients on improving bad habits. In the end, she notes, clinicians and leaders need to appreciate the importance of policy in supporting clinical goals. The conversation continues with the group discussing what Louise calls “fun facts” about common unhealthy foods. For the final question, Roger asks the panelists for one piece of advice to be utilized by providers seeking to push behavioral change in their patients. Surf on for their key takeaways.
Co-chairs Shira Zelber-Sagi and Mike Betel and panelists Tom Marjot and José Willemse, all from the EASL Congress session "Patient Experiences in Clinical Settings," join Louise Campbell to the need for resources that allow MASLD patients to access shared experience programs and holistic MASLD support programs.
This final conversation focuses on shared experience and holistic MASLD support programs. It starts with Tom suggesting that shared experience is a pivotal factor in patient support groups and patient-based supportive care. He goes back to viral hepatitis, where many of the patients had common background challenges related to the disease. In viral hepatitis, patients who have been treated successfully become integrated into the care community. Nothing like that happens in MASLD at this time. Louise comments this would be particularly useful due to stigma around the disease, stigma that successfully treated patients have overcome.
Louise points out that Michael makes extensive use of shared experience videos, such as this month, when he invited patients to follow him on a "30-day glucose challenge." Michael says that he gets unsolicited notes about how helpful the approach is, along with diet recipes. He agrees with Tom that a viral hepatitis model might provide help here.
Mike discusses the idea of metabolic disease support programs that take a more holistic approach and place MASLD in a broader, multi-disease context. Shire likes the holistic approach as well, including a focus on mental health. Tom agrees with the basic approach, commenting that the multitude of possible issues is what makes MASLD so tricky.
As the conversation wraps up, two final themes emerge: (i) physicians must be actively curious in exploring each patient's needs if therapy is to succeed, and (ii) joint goal setting is an excellent strategy for driving incremental changes in behavior.
Co-chairs Shira Zelber-Sagi and Mike Betel and panelists Tom Marjot and José Willemse, all from the EASL Congress session "Patient Experiences in Clinical Settings," join Louise Campbell to discuss ways that socioeconomic and psychological issues impact the dynamic of the physician-patient consult, and, as a result, often patient adherence to therapy.
This conversation starts with Shira asking Tom whether he addresses diet with his patients and, more importantly, whether he does so in the context of socioeconomic challenges, such as not recommending food that is too expensive for the patient. Tom says "Yes" to the first part, about diet and nutrition discussions and encouraging all patients to adopt a more healthy lifestyle, but, he says, not enough about socioeconomic issues. He feels that may be changing, though, based on the increasing discussion of food insecurity at conferences. The two agree that sensitivity in the topic is growing and needs to grow more in the years ahead, and also that while they are tailoring their discussions to address these issues, they can do more. Shira has begun to simplify her recommendations: fewer foods and less preparation time. Tom agrees this is a good idea.
Tom notes that he is focusing more these days on unemployment, social isolation and what he describes as social "unmet needs." He cites figures that 80% of the patients in a liver clinic have unmet needs and that improving social engagement can affect health. Mike asks whether the providers consider mental health, particularly given how important behavioral support is to treatment. Does Shira or Tom recognize mental struggle when the patient is sitting in front of them? Tom says this is an excellent question and identifies the three items patients in large studies say they seek in this realm: (i) education, (ii) reduction of stigma, and (iii) better psychosocial support. Mental health challenges are linked to unmet needs which, again, are linked to poor liver health. Tom believes the UK system does a good job of identifying this issue at the primary care level. Shira agrees this is important and, in her case, involves using quiet, probing questions in a sympathetic tone.
Louise asks whether Tom or Michael have observed MASLD-specific patient support groups in their regions. Both report that there are liver support groups, but nothing yet as specific as MASLD.
Co-chairs Shira Zelber-Sagi and Mike Betel and panelists Tom Marjot and José Willemse, all from the EASL Congress session "Patient Experiences in Clinical Settings," join Louise Campbell to discuss strategies and questioning styles that can improve the dynamic of the physician-patient consult.
This conversation starts with Tom stating that having multidisciplinary treatment teams would provide tremendous benefits in terms of being prepared for patients and fully responsive to the issues they are likely to raise. Jose agrees but adds that many countries have only a few nurses and no ability to create these kinds of teams.
Shira states that every physician should learn the principles of motivational interviewing. The key to this is asking open questions that allow the patient to respond fully without feeling judged or steered in a specific direction. This enables the patient to share unhealthy behaviors, which they might not do if the physician admonished them in advance. Tom agrees with the positive tone, saying that so much of the physician's role is all about trying to enthuse the patient to take control of lifestyle factors.
Along a similar theme, Mike notes the importance of tailoring care and questions to the individual patient. He points out that while 10,000 steps/day might be a goal, for some patients, it will feel so unattainable as to be demoralizing. Shira points out that an open question would start by asking the patient what goal is reasonable, and Jose follows by sharing an example of a patient who "hated" all exercise. José found a way to motivate the patient with simple, timely reminders that this was for the liver, and that the liver would be appreciative. Louise adds that changes in activity if the patient can define them as "fun."
Co-chairs Shira Zelber-Sagi and Mike Betel and panelists Tom Marjot and José Willemse, all from the EASL Congress session "Patient Experiences in Clinical Settings," join Louise Campbell to discuss some of the key dynamics shaping the physician-patient consult.
This conversation starts with Mike asking Tom whether he reviews the patient's history before the visit. Tom says he does so because he considers preparation vital to a successful consult. That said, Tom notes the importance of being responsive to the conversation rather than using the chart review to decide the outcome of the visit. He provides some empathetic detail about how important the visit is to the patient and, as a result, how important that he be responsive as well as prepared.
José agrees, provides more color, and notes what she considers the most important question a physician can ask a patient: "How are you feeling today?" To José, asking that question just one time a year can change he entire dynamic of the relationship.
Tom then notes the scarcity of time and the double-edged demand this creates for each visit: plan in advance to use time as productively as possible, but once the patient is in the consult, give it all the time it needs.
After José makes a point about the importance of using language precisely, Louise joins the conversation to describe the consult as "like speed dating," with both sides having a scare few minutes to make a relationship that will be pivotal to the patient.
Co-chairs Shira Zelber-Sagi and Mike Betel and panelists Tom Marjot and José Willemse, all from the EASL Congress session "Patient Experiences in Clinical Settings," join Louise Campbell to provide an overview of issues in physician-patient communication.
The conversation itself has two elements. It starts with first-time surfers Tom Marjot and José Willemse introducing themselves to listeners. After that, Shira starts by discussing the EASL Congress session within the context of a broader collaboration called "EASL Patient Synergies." This program led to the creation of the Patient and Advocate Forum as the EASL Congress, which led to this program. She says this year's program "worked" in developing "very interesting and fruitful and open dialog between patient and patient representatives and physicians," focusing on unmet patient needs and the roles various providers can play in addressing these. Mike shares one of his key takeaways: how fearful patients are when approaching physicians and how little information they share.
Mike recalls a comment Tom made during the session that if a patient ever told him, "What you just said hurt me or made me feel bad," that would have more impact on him than, as Tom puts it, "an entire weekend at a stigma workshop." Tom describes three levels at which to address patient stigma. Two of these, public policy and patient advocacy, are well known, but the third, improving direct physician-patient interaction, may be more vital and is underappreciated today. If patients provided direct feedback to Tom when Tom was communicating poorly, he says, he could adjust with the very next patient. Today, though, he doesn't get that kind of feedback.
Jose sees this as a two-way problem. Yes, most patients are fearful and do not share what they are thinking with the provider, but the reverse is true as well. When a patient shares feelings with a provider, the provider may not be equipped to handle it. She makes this point about provider insensitivity or failure to listen with two powerful vignettes.
Tom recalls Jose telling him in Milano that when the physician turns off the computer screen, it changes the entire dialogue with the patient. He has begun to do so, and it works! Jose makes a couple of points about this. First, simply asking that patient, "How do you feel?" and engaging with the answer makes the patient more satisfied with the visit. Second, this speaks to the idea that physicians do not realize how important they are in the lives of their patients.
00:00:00 - Surf's Up: Season 5 Episode 23
During SurfingMASH's wrap-up interviews from the EASL Congress (S5 E19), Louise Campbell and Mike Betel mentioned a session Mike co-chaired on challenges in provider-patient communications. Today, the other co-chair, Shira Zelber-Sagi and panelists Tom Marjot and Jose Willemse join Louise and Mike to return to this topic.
00:13:34 - Discussing the EASL Congress session
Shira describes EASL Patient Synergies, a broad collaboration to develop open, solution-centered dialog focusing on what patients need in working with providers. Mike shares a key takeaway.
00:16:31 - Stigma in what doctors say to patients
This section covers the issue of physician saying things they do not realize patients find hurtful. If the patient would share their discomfort, the provider could adapt on the fly. Jose sees this as a two-way problem: patients do not share feeling, but when they do, most providers cannot handle them.
00:19:40 - Sending signals of attentiveness
This section covers the positive impact when the physician does something simple like turning off the computer screen and the reasons why.
00:21:06 - Preparing for a patient consult
Tom considers prior preparation and chart review vital to a successful consult. Panelists note how much more important the consult is to the patient compared to the provider.
00:29:23 - Structural improvements for patient consults
To Tom, multidisciplinary treatment teams provide tremendous benefits in patient preparation and responsiveness, but Jose notes that many countries lack the number of nurses necessary to do so.
00:30:57 - Motivational Interviewing
Shira suggests that every physician learn the principles of motivational interviewing: asking open questions with no emotional valence. This enables the patient to share unhealthy behaviors. The panel agrees, noting that physicians can motivate and that they are most effective when tailoring to the individual.
00:38:10 - Food insecurity as risk factor
Shira asks Tom whether and how he addresses diet with his patients and, more important, he does build socioeconomic factors into the decision analysis. Tom says "Yes" about diet and healthy lifestyle, but, he says, not enough about socioeconomic issues. They agree that awareness of the impact of food insecurity is growing and needs to grow more.
00:41:10 - Assessing mental health and quality of psychological life
The group considers the idea that a large majority of patients in a liver clinic have unmet economic or mental health needs, and discusses what to do to improve social engagement. Tom identifies the three items patients in large studies say they seek. The group discusses the idea that they see liver support groups, but none are MASLD-specific.
00:46:03 - The value of lived experience in providing care
This section explores shared experience as a pivotal factor in patient-based supportive care, similar to viral hepatitis, where successfully-treated patients become integrated into the care community.
00:49:03 - Holistic metabolic disease support programs and wrap-up
Mike suggests that MASLD support programs take a more holistic approach that places MASLD in a broader context. Shira suggests adding a focus on mental health.
As the conversation ends, two final themes emerge: (i) physicians maximize success by being actively curious in exploring each patient's needs; and (ii) joint goal setting is an excellent strategy to drive behavior change.
00:54:41 - Question of the Week
What structural or educational changes do you anticipate will improve provider-patient communication significantly, and will these changes require more from the provider, the patient or both?
00:55:14 - Business report
Information on future episodes plus a shout-out to Indonesia.
In this week's episode, Jeff Lazarus discusses the idea that the MASH community, including patient advocates, live in a "bit of a bubble," where the clinicians with whom they interact are part of the MASH community. Last year's ICER Public Comments session exposed them to an FDA Advisory Board of hepatologists...and it was a very different experience. Last year's conversation notes reveal what happened and the advocates' reactions:
In March 2023, Jeff McIntyre (GLI) introduced a draft report from the Institute for Clinical and Economic Review (ICER) on resmetirom and obeticholic acid for NASH. The Surfers dedicated an episode to expand on the contents, its shortcomings and potential implications with special guests Veronica Miller (Liver Forum) and Hannah Mamuszka (Alva10). In this conversation, SurfingMASH revisits the topic after a public comments session that took place last week. In doing so, patient advocates and friends of the podcast Mike Betel (Fatty Liver Alliance), Tony Villiotti (NASHkNOWledge) and Wayne Eskridge (Fatty Liver Foundation) join co-hosts Louise Campbell and Roger Green to share a range of impressions.
Roger begins by asking the group how the word empathy fits into this discussion. Tony shares that he was upset by the majority viewpoint of 15 featured voting members on a number of different issues. For example, 40% of these voting members suggested that a drug approval would have no impact on a caregiver’s life. Tony asserts the importance behind people needing to be aware of the impact of NAFLD/NASH not only on the patient, but also the families and those close to them. Speaking from personal experience, Wayne shares that he was perplexed on the document's position that NAFLD/NASH is not considered to be a progressive disease. This leads Louise and Roger to insert comments around the pricing and economic analysis surrounding the discussion. As the conversation winds down, Mike returns to the conundrum of the voting results. Listen on to hear why his reaction was, “I literally fell out of my chair.”
In this closing conversation, Healthy Livers, Healthy Lives Chair Jeff Lazarus and Surfers Jörn Schattenberg, Louise Campbell and Roger Green discuss the upcoming United Nations General Assembly side event and consider ways listeners can support the "Healthy LIvers, Healthy Lives" coalition.
Jeff discussed this impact on global care when the World Health Organization develops and releases a global health sector strategy. One key goal in public health is to lobby for a MASLD strategy. To that end, Healthy Livers, Healthy Lives is holding a side event at the United Nations General Assembly meeting in mid-September.
00:40:41 - Presenting MASLD to politicians
One challenge in educating policymakers about MASLD is that people do not die from MASLD. One recent example: policymakers did not respond to the spread of SARS-CoV-2 until COVID-19 produced massive numbers of deaths.
When asked, Jeff draws the chain from MASLD to MASH to cirrhosis and end-stage liver cancer and notes that we are already seeing MASLD as a leading cause of liver transplant.
Roger suggests that Jeff reframe the issue to be about how many people die with MASLD, not from MASLD. Jeff believes this simple change may change the dialogue.
00:43:06 - How listeners can support this initiative
Roger asks Jeff how listeners can support the Healthy Livers, Healthy Lives initiative. Jeff suggests that we all be careful to name the disease and let people know how easily MASLD can be identified and treated. For those who work in related areas or help set policy for their organizations, make sure that MASLD is included and, whenever possible, linked to diabetes, obesity, and other relevant metabolic conditions.
00:44:58 - LiverAIM and exit.
As his closing comment, Jeff discusses LiverAIM, the largest European Commission-funded liver project in 26 years. (Jörn and Maja Thiele, who is leading the 100,000-person randomized clinical trial, discuss this in Episode 15.) Roger commits to producing an episode on LiverAIM this fall.
After Jeff departs, Jörn restates the importance of working with colleagues like Jeff who can systematically develop public health approaches and drive policy change from the top down. Roger agrees that a top-down approach can be extremely valuable, but may have limits in primary care. He suggests that professional organizations also need to bring allied health providers into the dialogue.
Healthy Livers, Healthy Lives Chair Jeff Lazarus joins Jörn Schattenberg, Louise Campbell and Roger Green to discuss the value of the updated EASL/EASD/EASO MASLD clinical practice guidelines and consider the role of Big Data in early MASLD screening.
Roger asks Jeff whether he considers the updated MASLD CPG a step forward. Jeff praises the guidelines as "amazing" and suggests that one reason is that EASD and EASO are partners in drafting and promoting them.
Roger's next question to Jeff addresses the idea that Big Data can provide a set of common variables that will outperform FIB-4 in predicting which patients are at high risk of MASLD or MASH, as Hannes Hagstrom discussed in Episode 17 this year. Jeff believes we can use more data than only the FIB-4 today but that, in the long run,we need better biomarkers to simplify the system. Jörn adds that having historical blood tests will allow for that kind of analysis, which should be superior to FIB-4. Jeff points out the challenge: not all variables are collected in each country. Bottom line: the solution must be simple and realistic to apply in practice in different countries.
Healthy Livers, Healthy Lives Chair Jeff Lazarus joins Jörn Schattenberg, Louise Campbell and Roger Green to discuss some of the specific structural challenges that confront global MASLD public policy, along with some promising local activities.
Louise observes that, in her experience, primary care practitioners appreciate the support that specialist nurses can bring in educating providers about the disease and patients about how to better support themselves. Jeff responds that these are good findings as individual cases, but to make major changes in the field, we need large-scale, top-down innovations. One thing that, oddly, works in MASLD's favor is that most patients with advanced MASLD will have concomitant diseases requiring involvement with other specialties. Today, teams are looking at system issues to find the largest, most intractable structural problems so that solutions can emerge. After that, "we'll start to see bigger and faster improvements in the field."
Jeff talks about several positive things happening in New York. First, he mentions a New York Times article about junk food and how manufacturers target aggressive marketing to poor and marginalized populations, with the net result that these populations have processed and ultra-processed foods making up a large share of their diets. Also, a "visionary" health commissioner is creating a program, Healthy NYC, with the goal of increasing life expectancy by reducing specific diseases.MASLD is not part of the effort today but with clinician support. we can get there over time.
Earlier, Jeff had commented about the ease of implementing the FIB-4 test. Now, Roger raises the issue again, this time mentioning that SurfingMASH guests from ex-US markets have mentioned that ALT is not a standard test in their countries and asks Jeff if MASLD is making progress here. Jeff discusses the debate around this issue.
Healthy Livers, Healthy Lives Chair Jeff Lazarus joins Jörn Schattenberg, Louise Campbell and Roger Green to discuss why political will is so important in overcoming inertia and obstruction in global MASLD public health policy.
Louise notes that she left NHS because of obstruction against earlier stage efforts to promote liver health and asks how to achieve these goals. To Jeff, it all depends on political will. He provides an example from viral hepatitis to prove his point.
Roger asks how to motivate primary care practitioners who are overloaded with tasks they need to complete during short, overly scheduled patient visits.
Jeff notes this is a challenge today, with a solution that lies in education that not only teaches about the disease but also stresses the cost of inaction. To Jeff, teaching FIB-4 to primary care and automating the algorithm to make it available in every electronic patient record is the minimum we should strive for today.
Jörn focuses on the cost of inaction from a different direction: physicians who are afraid they will demoralize patients when they diagnose a disease with no available treatment. Jeff responds, "Do we not raise awareness because we don't have out-of-the-box solutions?" He goes on to describe different types of solution that might work for a patient, ranging from digital apps to linking patients to social agencies that can provide support and services. Jeff notes that "the field will need to change as we find more patients," due to increased demand on public health systems and social agencies.
Healthy Livers, Healthy Lives Chair Jeff Lazarus joins Jörn Schattenberg, Louise Campbell and Roger Green to discuss how the coalition came into existence and to describe two initiatves aimed at increasing early screening.
Jeff starts the conversation by describing the "bit of a bubble" in which the MASLD community lives: great news and lots of excitement within, but very limited exposure to related metabolic specialties (endocrinology, primary care, cardiology) and limited awareness among the people and organizations that shape public health policy.
Jörn adds that Jeff has been working for the last 4-5 years to create a multi-stakeholder coalition to promote liver disease to relevant professional societies and public health policy shapers. Jeff notes that patient advocates, clinicians, and professional societies each have a pivotal role to play in advancing liver care, particularly MASLD care.
Healthy Livers, Healthy Lives is a coalition of four major professional organizations (AASLD, ALEH, APASL, and EASL) along with other partners, like the Indian National Association for the Study of the Liver (INASL), to raise awareness within the liver field and also other metabolic specialties. Jeff describes it as "really trying to be an open, transparent, engaging, ambitious and aspirational coalition" with a light structure and just a few areas of focus over the next year: World LIver Day on April 19, the World Health Assembly, and the UN General Assembly.
Louise asks about efforts to promote early screening that will help patients get care earlier in their disease progression. Jeff mentions two: a project to "double the diagnosis" over the next 3-4 years, and another project to identify all the concomitant conditions with sufficient cost of disease to merit screening everyone in that group. The latter will provide the kind of data to which public policy makers respond best.
00:00:00 - Surf's Up: Season 5 Episode 22
Jeff Lazarus joins Jörn Schattenberg, Louise Campbell and Roger Green to discuss Healthy Livers, Healthy Lives, a coalition of four major professional organizations (AASLD, ALEH, APASL and EASL) and other partners. This coalition works with other specialties to create global public health awareness and drive "top-down" solutions that are pivotal to stemming the MASLD Tsunami.
00:06:48 - The need for a MASLD public health coalition
Jeff starts the conversation by describing the environment in which the MASLD community lives today: great news and energy within, but minimal exposure among related metabolic specialties and public health policy shapers.
00:11:55 - Healthy Livers, Healthy Lives
Jeff describes the structure and goals of Healthy Livers, Healthy Lives.
00:13:32 - Two initiatives to increase early screening
In response to a question from Louise, Jeff mentions two efforts: a project to "double the diagnosis" over the next 3-4 years and another to identify all the concomitant conditions with sufficient disease cost to merit screening everyone living with that condition.
00:16:39 - Political will and structural change
Louise asks how we can overcome obstruction within the system to promote liver health. To Jeff, it all depends on political will, the energy that converts successful localized strategies into large-scale, top-down innovation. The solutions to the most significant, most intractable structural problems that evolve this way can drive "bigger and faster improvements in the field."
00:28:40 - Good things happening in New York
In this context, Jeff shares how a visionary health commissioner in New York has created the Healthy NYC program to increase life expectancy by reducing specific diseases.
00:33:00 - The updated MASLD CPG
Jeff praises the updated MASLD CPG guidelines as "amazing" and suggests that one reason is that EASD and EASO are partners in drafting and promoting them.
00:35:40 - Big Data-drive screening solutions
This section explores whether and how Big Data can provide a set of standard variables that will outperform FIB-4 in predicting MASLD risk (see S5 E17). Jeff and Jörn identify the benefits and challenges of this approach.
00:38:38 - The upcoming U.N. General Assembly MASLD side event
Healthy Livers, Healthy Lives is holding this event at the U.N. General Assembly meeting in mid-September. The goal is to push the World Health Organization to develop and release a global health sector MASLD strategy.
00:40:41 - Presenting MASLD to politicians
One challenge in educating policymakers about MASLD is that people do not die from MASLD. Sadly, large death counts produce public sector action, as we all saw with COVID-19. Suggestion: Reframing the issue as to how many people die with MASLD, not from MASLD, may make the story easier to tell.
00:43:06 - How listeners can support this initiative
Roger asks Jeff how listeners can support the Healthy Livers, Healthy Lives initiative. Listen to hear Jeff's suggestions.
00:44:58 - LiverAIM and closing comments
Jeff mentions LiverAIM, the largest European Commission-funded liver project in 26 years (see S5 E15). Jörn restates the importance of working with experts in developing public health approaches that drive policy change from the top down. Channeling Louise, Roger suggests that professional organizations need to bring allied health providers into the dialogue.
00:50:03 - Question of the Week
Roger asks what listeners believe they can do in their own organizations and lives to support the goals discussed today.
00:50:36 - Business Report
News on next week's session, Roger's office hours, and the Vault conversation.
This week's vault conversation looks back 17 months when Ken Cusi joined co-hosts Louise Campbell, Jörn Schatenberg and Roger Green to discuss the revised AASLD Practice Guidance that had been issued the previous week. At the time, here was SurfingMASH's summary of the conversation:
Late last week, AASLD published new practice guidance *on the clinical assessment and management of NAFLD. The Surfers convene with Ken Cusi, who contributed to the previous iteration published in 2018, to explore its key features and implications. The updated document reflects the many advances pertinent to any practitioner caring for patients with NAFLD. This conversation focuses on the impact this guidance may have on patients: will it make a difference and if so, how?
Ken asserts his position that both patients and providers need to be educated on solutions available today. Measures range from effective diet modifications to bariatric surgery and anti-obesity drugs. Louise Campbell reminds us that not all patients interact with physicians and that nurses, dieticians, and other allied health professionals experience more numerous contact points in terms of co-morbidity management. She asserts that guidances and guidelines need to make an effective impression on the frontline professionals, caretakers and even the patients themselves. This prompts Ken to share some exciting news with regard to the ADA formally recognizing NASH as a problem associated with diabetes. He reveals that he is chairing a committee that will work to create a consensus statement on this subject through consulting an array of stakeholders. Notably, they are inviting the participation of dieticians, diabetes educators, pharmacy representatives, obesity management leaders, primary care representatives and hepatologists, among other groups. Ken expresses his optimism for the momentous energy and convergence of fields in an unprecedented effort to collectively combat Fatty Liver diseases. Jörn adds that such collaboration will drive stronger patient advocacy and better education about what specific questions they should be asking their treaters.*
In this closing conversation, updated MASLD CPG co-authors Frank Tacke and Elisabetta Bugianesi and podcast co-hosts Louise Campbell and Roger Green consider what the guidelines might foretell in changes in provider education, structure of patient visits and treatment in less affluent or medically advanced countries.
The last set of questions begins with Roger asking what kinds of changes the authors would like to see in the healthcare system. Frank likes Louise's idea of cardiometabolic pathological nursing and, more broadly, motivating physicians and nurses to view MASLD holistically. Elisabetta envisions a world where not only are there multidisciplinary teams, but each physician asks what they can do for the "liver/kidney/metabolic alliance." Frank describes this as "like a dream" and would like a world where the patient comes to the hepatologist for a cardiac workout, endocrine workout, nutritional counseling and other holistic support. It would also help get the correct patients triaged in primary care or referred to specialists.
Roger asks whether Tumor Boards in oncology serve as a model for integrated metabolic disease treatment. Frank says in his institution, boards exist for cirrhosis patients but will never be realistic for the number of patients needing treatment.
As the episode winds down, several issues emerge. Louise wonders how these guidelines might be used in less affluent countries or those with less advanced/resourced healthcare systems. Elisabetta stresses the importance of generating awareness. Roger asks how the guidelines will incorporate updates for future drugs and bariatric surgery data; Frank feels this will not be a particular challenge and cites the upcoming data on obesity drugs and the SPECIAL study as information that might drive updates. Frank also suggests that all listeners should download the guidelines (the link is listed on the Surfing the MASH Tsunami web page.) And with one final set of congratulations to the authors, the episode ends.
For most of this conversation, updated MASLD CPG co-authors Frank Tacke and Elisabetta Bugianesi discuss key issues related to pharmacology and prescribing choices. At the end, the focus shifts to the guidelines' overall benefits and some new kinds of education they call for.
The conversation starts with co-host Roger Green asking about key issues from the pharmacology section. Frank states that one benefit of the CPG is the clarity around the point that optimal treatment for a co-morbidity must involve thinking holistically about the liver in the overall metabolic context.
Elisabetta notes that while no drugs are efficacious for cirrhosis, the document does report that some drugs are safe for these patients, although sometimes with adjusted doses.
Frank concurs that the document provides guidance on managing patients with end-stage liver disease and also discusses how to manage cirrhosis and its various complications. Elisabetta notes that these can be the most difficult patients to screen for HCC because "the fat liver is sort of foggy."
This leads co-host Louise Campbell to discuss a point that arises frequently on this podcast: the positive value of simply stabilizing disease through medication and lifestyle.
Roger adds that many primary care physicians in the US find managing metabolic multi-comorbid patients confusing and frustrating. These guidelines, with an integrated vision of metabolic diseases and the idea that stabilization might be a sound strategy, simplified the perceived task.
Louise suggests that these guidelines "pinpoint...a role of the potential future" for nurses who can support the entire cardiometabolic syndrome. As she points out, even hepatology nurses are "not good at fatty liver disease." This document might drive a curriculum for such a specialization.
In this conversation, updated MASLD CPG co-authors Frank Tacke and Elisabetta Bugianesi discuss some of the guidelines' key goals and issues surrounding the screening, diagnosis and management of MASLD patients.
As the conversation starts, co-host Roger Green says that he, too, was impressed that all these adjustments were made within a month at the end of the process. Frank praises the "very engaged Delphi panel" that reacted and voted quickly, and fairly consistently. He proceeds to discuss how the Delphi panel was formed.
From here, the discussion shifts into its key focus: patients. Roger asks for high points in the discussion of screening, diagnosing and managing patients. Elisabetta starts by stating that the resmetirom approval is creating a great push for screening because physicians feel that there is something they can do to help their patients. She describes an approach that begins with FIB-4, proceeds to VCTE and offers two paths for patient management. This should help the system identify patients before cirrhosis or HCC in pre-cirrhotic patients.
Frank points out that this set of guidelines does not rely on biopsy for risk assessment, which he terms "a major breakthrough."
Co-host Louise Campbell lauds the document's approach to diet advice, specifically the broad range of diets that will make it valuable worldwide and for primary care physicians to work from.
Frank adds that the guidelines have adjusted thresholds and other "adaptations to the ethnic background of the individual." This included considering the socioeconomic factors of a target country.
In this conversation, updated MASLD CPG co-authors Frank Tacke and Elisabetta Bugianesi explain how the guidelines process benefitted from the close collaboration between EASL, EASD, and EASO.
The conversation starts with Elisabetta conveying the "big advantage" that came from this collaboration. The presence of the three organizations conveyed the need to create a common way to manage patients with MASLD, many of whom live with diabetes and obesity. The guideline also used the new nomenclature, which highlighted the metabolic root of the disease.
Frank notes that the three societies have their own approval processes, which led to increased rigor from having to meet three standards. He concurs that the collaboration and approach strengthened the guidelines by putting the liver in the broader context on the disease.
After co-host Roger Green notes how much more complete this is than the previously released clinical care pathway documents, co-host Louise Campbell asks whether the guidelines will increase the profile of liver disease in other specialties. Elisabetta refers to Ken Cusi's view that "it takes time," but points out two reasons for this integration to be smoother: (i) "you can't hide cirrhosis" and (ii) diabetes and other components of the general metabolic syndrome are pivotal risk factors not only for cirrhosis, but also HCC.
Frank had been concerned at first that the name change would "lose the other societies," but the reverse was true: putting "metabolic dysfunction into the center of disease definition" links overall cardiometabolic risk to liver disease. Further, the guideline has a chapter on prevention and case-finding strategies that are relevant to primary care and diabbetology or endocrinology practices.
Earlier in the episode, Louise commended the guideline for including resmetirom even before its approval in Europe. Frank thanks her, and notes that the decision to add resmetirom came after US approval and was included within the month before the guidelines were released, similar to discussion of how some glucose-lowering drugs could help treat cardiometabolic comorbidities.
Two of the co-authors of the upgraded MASLD Clinical Practice Guidelines, Elisabetta Bugianesi and Frank Tacke join Louise Campbell and Roger Green to discuss the guidelines.
The theme for the conversation is "introductions". First, the audience is introduced to co-authors Elisabetta Bugianesi and Frank Tacke, neither of whom has Surfed the Tsunami before. Both Elisabetta and Frank have unusual answers to the "one thing our audience would not expect about you if you didn't tell them" question, although in very different ways.
After this, the Surfers and guests begin the process of introducing us to the updating process. Frank Tacke describes when the idea to upgrade arose, where it came from, and the two mechanisms, co-authors and Delphi panels, that became the foundation for the upgrade.
00:00:00 - Surf's Up: Season 5 Episode 21
One important session at the EASL Congress 2024 involved the presentation of the new MASLD Clinical Practice Guidelines. CPG co-authors Elisabetta Bugianesi and Frank Tacke join Louise Campbell and Roger Green to share their perspectives on the guidelines' development some key recommendations.
00:09:36 - Revising the guidelines
Roger asks the co-authors to describe the process that led to the 2021 decision to revise the guidelines. EASL was the initial driver; EASD and EASO joined the process. They formed a committee of 15 leaders and assembled a Delphi panel of 46 individuals from different stakeholder communities.
Elisabetta describes the "big advantage" of this collaboration: it conveyed the need for a common way to manage co-morbid patients with MASLD. To Frank, this approach strengthened the guidelines by putting the liver in the center of metabolic disease.
Louise asks whether the guidelines will increase the profile of liver disease in other specialties. Elisabetta says "it takes time" but says that the nature of cirrhosis and HCC might make this easier.
00:19:07 - Adding resmetirom before approval
Earlier, Louise praised the inclusion of resmetirom in the guidelines, Frank notes that this section was added to the guidelines within a month before their release and praises the "very engaged Delphi panel" that reacted and voted quickly. He proceeds to discuss how the Delphi panel was formed.
00:23:24 - Major issues in screening, diagnosing and case-managing patients
Elisabetta starts by saying that resmetirom's approval created momentum for screening. She says the approach identifies patients before cirrhosis or HCC in pre-cirrhotic patients. Frank points out "a major breakthrough": these guidelines do not rely on biopsy.
00:28:04 - Non-medical factors
Louise lauds the document's the broad range of diets that will make the document valuable around the world . Frank adds that the guidelines have adjusted thresholds adapted to the ethnic and socioeconomic background of the individual.
00:30:52 - Pharmacological issues in the new CPG
Frank starts the pharmacological discussion noting that the CPG drives holistic thinking about the liver in a metabolic context. Elisabetta notes that while no drugs are efficacious for cirrhosis, the document does report that some drugs are safe for these patients, although sometimes with adjusted doses.
00:33:39 - Screening for cirrhosis
Frank concurs that the document provides guidance on managing patients with end-stage liver disease and also discusses how to manage cirrhosis and its various complications. Elisabetta says that HCC can be hard to find in a fatty liver.
00:36:36 - Cardiometabolic nursing as a future training and specialty
Louise suggests that these guidelines "pinpoint...a role of the potential future" for nurses who can support the entire cardiometabolic syndrome. This document might drive a curriculum for such a specialization.
00:38:48 - What adjustments would you like to see in the healthcare system?
The last set of questions begins with Roger asking what kinds of changes the authors would like to see in the healthcare system. The discussion revolves around a "cardiometabolic" perspective but in terms of nurse training and the care provided in a hepatologist's office.
00:43:18 - Winding down
As the conversation winds down, each panelist offers a final comment or question.
00:47:59 - Question of the Week
Roger asks how readily listeners believe the guidelines will be implemented, and which sections will be easiest and hardest to implement.
00:48:32 - Business Report
The next EASL Congress review episodes, starting office hours, and a vault discussion from 2023's clinical care pathway document.
In this conversation from July 2023, Stephen Harrison, Jörn Schattenberg and Roger Green discuss the implications of presentations on the FGF-21 agent efruxifermin and the dual GLP/glucagon agonists pemvidutide and efinopegdutide.
Here is the description Roger wrote for the original conversation:
In this session, conversation shifts from resmetirom to Mazen Noureddin's "NASH Monopoly" game and focuses on the value of FGF-21s and glucagon agents. Stephen posits two comments about GLP-1s. First, there is now adequate data suggesting that GLP-1s will not melt away all liver fat and as a result lead to dramatic fibrosis regression. Second, we know from a small sub-cohort of patients in Akero's SYMMETRY trial that patients already on fairly low doses of GLP-1s saw what Stephen describes as an 'incredible' and incremental benefit for the FGF-21 agent, efruxifermin. The group notes that while glucagon dual and treble agents are likely to produce dramatically more robust results in weight loss and liver defatting than GLP-1s alone, they still seem unlikely to 'usurp the need for other types of agents.' From here discussion considers the FGF-21 class. Stephen notes that two drugs, efruxifermin and pegozafermin, have demonstrated significant efficacy against fibrosis. As the conversation concludes, the panelists agree that earlier, more aggressive screening to arrest cirrhosis will become pivotal and will not occur until the right drug becomes available.
Mazen Noureddin and Naim Alkhouri join Jörn Schattenberg and Roger Green to discuss some of the other major drug development stories from the EASL Congress 2024, with special focus on denifenstat, ION-224 and TAK-227, and to review the SPECIAL study on bariatric surgery and cirrhosis.
The panelists concur that all three of these agents have potential value in therapy. Naim expresses some concern about how broad denifestat use will be based on its side effect profile. Later in this conversation, Mazen belives that denifenstat has broad potential for use, given that the most prominent side effect, hair thinning, appears transient and readily manageable. He also notes that denifenstat's impressive results were based on Intent to Treat analysis, which is more rigorous.
Naim states his interest in the ION-224 agent based on its mode of action, which is RNA interference. He also discusses SPECIAL, a study he conducted with the bariatric surgery group at Cleveland Clinic. This study, which evaluated patients with cirrhosis at the time of surgery, demonstrated a 72% risk reduction in major adverse liver outcomes over a 10-year period and 80% risk reduction in decompensation.
Jörn discusses a study he presented on TAK-227, a TG2 inhibitor originally developed for celiac disease. Early results here are quite promising and, as Aleksander Krag mentioned in S5 E17, demonstrates exciting potential for collaboration with drug developers for other diseases.
As the conversation ends, Roger asks Mazen and Jörn what they consider likely to be the biggest MASLD stories at the AASLD Liver Congress in November. Mazen selects the Phase 3 ESSENCE study for semaglutide, while Jörn suggests NITs.
Mazen Noureddin and Naim Alkhouri join Jörn Schattenberg and Roger Green to focus on the role FGF-21s will play in long-term advanced fibrosis treatment: induction or long-term therapy...or might we even think of the class as being able to produce a "MASH cure?"
Responding to Naim's comment closing the previous discussion, Mazen questions why we regard FGF-21 agents as induction therapies given that it appears to be as well tolerated as the oral agents and maintains such efficacy over time. In fact, he adds, its sustained efficacy might make it possible for livers to eliminate fibrosis and return to their "normal" state, almost like a "cure."
Jörn adds a comment about pegozafermin, another FGF-21 in development. Jörn notes that this agent is a pegylated molecule, which makes it different from efruxifermin. He notes that NITs show sustained enzyme response at 48 weeks. Mazen reiterates his optimism about the FGF-21 class and reminds us that there is a third FGF-21 in development.
Roger raises Michael Charlton's question (Season 5 Episode 11) whether an induction therapy strategy for FGF-21s might not work if removing the drug allows the MAS activity to return. On the other hand, he notes, it might take years for fibrosis to return. Mazen agrees that many unanswered questions exist, but reiterates his belief in long-term therapeutic value.
Naim Alkhouri and Mazen Noureddin join Jörn Schattenberg and Roger Green to discuss issues regarding incretin agonists and results from the efruxiermin late-breaker at the EASL Congress 2024.
Naim shares his general excitement about glucagon agents in general. He mentions that the efinopegdutide study included a semaglutide cell, which showed further reduction in liver fat vs. the GLP-1 agent.
Jörn comments on the high level of tolerability in the survodutide trials. Mazen shares his high hopes for GLP/glucagons and the triple agents. He goes back to review the survodutide data from the NEJM article.
Mazen shares the late-breaker data that Vlad Ratziu presented on behalf of Stephen. This is a 96-week, triple biopsy study showing dramatic, sustained fibrosis improvement with a 30% delta for one level and a 21% delta for two levels. Jörn notes that the triple biopsies are demonstrate the durability of the agent against fibrosis. Roger notes this is particularly encouraging because of the previous pegbelfermin data showing loss of efficacy and tachyphylaxis. Naim concurs and adds that if the two-stage drop in fibrosis can be sustained, this would be a "big deal for the field" that might lead prescribers to think about FGF-21 as indication therapy with a "more tolerated" oral later on.
Mazen Noureddin and Naim Alkhouri join Jörn Schattenberg and Roger Green to discuss the tirzepatide late-breaker at the EASL Congress 2024 and other "Twin-cretins," all of which are GLP-glucagon combinations.
"Twin-cretins" is the name Jörn has coined for agents with a GLP-1 agonist plus another incretin effect. Tirzepatide is a GLP/GIP agent, while survodutide and the agents discussed last year, pemvidutide and efinopegdutide, are GLP/gluagons.
Naim reviews the results of the tirzepatide late-breaker presentation. As expected, it showed high rates of MASH resolution. Naim does not feel it answered the question whether an incretin-agonist can achieve significant fibrosis regression without a direct liver effect, since it relied on a completer analysis that treated 3 of 10 non-completers as a success (in ITT, that would have been 0 out of 10). Again, glucagon has a direct effect; GIP does not.
This takes Naim back to the question of whether a GLP/GOP can have a meaningful effect on fibrosis. He notes that Stephen believed firmly that it could not, but there is a paradox in that bariatric surgery can produce a reduction in fibrosis. Naim notes that conclusive data will arrive later this year, so no one needs to decide now.
Mazen praises tirzepatide's effect on weight loss and safety and could prescribe it now, but the completer analysis has not persuaded him to prescribe to regress fibrosis, particularly given the lack of a dose response. He notes that "while I don't want to compare apples to oranges," he is more confident in the glucagon effect found with survodutide, pemvidutide and efinopegdutide. Jörn agrees.
Roger asks how prescribing decisions will change in a market where a significant share of US patients will have been prescribed semaglutide or tirzepatide before coming to the hepatologist. Naim comments that many of his MASH patients have been on GLP-1 already. He notes that since glucagon increases blood sugar, the ratio of GLP-1:glucagon is a key issue and difference between the three GLP/glucagon agents.
Naim Alkhouri and Mazen Noureddin join Jörn Schattenberg and Roger Green to discuss some of the new research on resmetirom at the EASL Congress 2024.
Mazen begins this discussion by covering a paper he presented on Stephen's behalf, looking at dose-response with resmetirom. The analysis indicated that PDFF and histology improvements at the 100mg dose were greater than at the 80mg dose. Mazen speculates that the higher dose might provide a greater anti-fibrotic response as well, although, in a world where biopsy is not required for prescribing, he doubts the study will ever be done. Jörn notes that the most important element of the study might be a demonstration of effect lasting at least 36 months.
As an aside, Mazen mentions a study from Samer Gawrieh demonstrating that dropping liver stiffness to <10kPa correlates with a 75% reduction in clinical liver events. He reports that resmetirom was a bit higher than 10 in Year 1, but dropped below for those patients continuing to Years 2 and 3.
At this point, Naim shifts slightly to compare modes of analysis: Completer Analysis vs. Intent to Treat.
His point is that Intent to Treat, which scores all non-completers as failures, will produce lower rates of response than a "completer" or "modified Intent to Treat" analysis, which either eliminates non-completers or assigns placebo-level response to them.
00:00:00 Surf's Up, Season 5 Episode 20
Naim Alkhouri and Mazen Noureddin join co-hosts Jörn Schattenberg and Roger Green to discuss major drug development stories from the EASL Congress 2024. They pay tribute to Stephen Harrison and proceed to groundbreakers.
00:08:16 - Presentations on Resmetirom
Mazen shares a paper he presented looking at resmetirom dose-response. The 100mg dose performed better than the 80mg dose. Jörn notes that the most important element of the study might be the demonstrated 36-month effect.
00:14:19- Implications of Different Analytical Modes
Naim compares different modes of analysis. Intent to Treat, which treats all non-completers as failures, will produce lower rates of response than a "completer" or "modified Intent to Treat" analysis, which either eliminates non-completers or assigns them placebo-level response.
00:16:12 - The "Twin-Cretins"
Jörn coined the name "Twin-cretins" for agents with GLP-1 agonism plus another incretin effect. Tirzepatide is a GLP/GIP while survodutide, pemvuditide, and efinopegdutide, are GLP/glucagons. Naim reviews the tirzepatide late-breaker presentation, which showed high rates of MASH resolution, but, as a completer analysis, might not have proven whether a GLP/GIP can achieve significant fibrosis regression. Naim notes that Stephen doubted strongly this was possible, but that bariatric surgery's effect creates a paradox. Mazen concurs, and states he is more confident in the GLP/glucagon agents. Jörn agrees.
00:23:09 - Implications of widespread GLP use
Roger asks how widespread prior patient use of incretins will affect prescribing. Naim states that many of his Rezdiffra MASH patients have been on GLP-1 already. He describes a key difference between the three GLP/glucagon agents in development.
00:24:20 - The previous GLP/glucagon studies
Naim expresses his excitement about glucagon agents in general. He mentions that the efinopegdutide study included a semaglutide cell, which showed a further reduction in liver fat compared to the GLP-1 agent.
00:26:44 - Safety of survodutide in cirrhosis
Jörn comments on the high level of tolerability in the survodutide trials. Mazen shares his high hopes for GLP/glucagons and the triple agents. He reviews survodutide data from the NEJM article.
00:29:41 - FGF-21s, starting with efrux data
Focus shifts to FGF-21s. Mazen shares data from the efruxifermin late-breaker, a 96-week, triple biopsy study showing dramatic, sustained one- and two-level fibrosis improvement. Jörn notes the design demonstrates durability, which Roger finds particularly encouraging given the pegbelfermin experience. Naim adds that a sustainable two-stage drop in fibrosis might position FGF-21 as induction therapy before long-term oral maintenance.
00:35:28 - Is a drug-based MASH "cure" possible?
Mazen wonders whether sustained FGF-21 efficacy might return livers to their "normal" state, almost like a "cure." Jörn briefly discusses pegozafermin, and Mazen notes that a third FGF-21 is in development.
00:42:22 - Wrap-up
The panel covers three other agents: the FASN inhibitor, denifenstat, Ionis's DGAT-2 antisense inhibitor, ION224, and Takeda's TAK-227, a TG2 inhibitor, plus the results of SPECIAL, a study evaluating the effect of bariatric surgery on people with cirrhosis. After these, Roger asks Mazen and Jörn what they consider likely to be the biggest story at AASLD in November.
00:53:03 - Question of the Week
Given this discussion, Roger asks what are likely to be the three most prescribed medications for MASH five years from now.
00:53:36 - Business Report
The next EASL Congress review episodes, how to attend recording sessions live, and a vault discussion from last year's EASL Congress wrap-up.
00:00:00 - Surf's Up: Season 5 Episode 19
During EASL Congress 2024, US-based Roger Green, conducted interviews with Mike Betel, Louise Campbell (twice) and Sven Francque from Milano. These interviews focused on the major MASLD themes and presentations at the event.
00:04:14 - Conversation with Mike Betel begins
On Wednesday, the first afternoon of the meeting, Mike Betel joined Roger from the convention center.
The first part of the conversation centered on the Patient Advocate session that Mike chaired with Shira Zelber-Sagi. The session's goal was to discuss barriers to addressing unmet needs in a clinical setting and explore potential solutions. Mike's key takeaway: patients around the world are having challenges getting personal attention and time from their treaters.
The rest of this interview touched briefly on other sessions Mike attended.
00:15:23 - First conversation with Louise Campbell
Roger's first interview with Louise took place late on Thursday. She described the "really nice vibe" of the meeting, dampened by the fact that Stephen Harrison is no longer with us.
The first session Louise chose to discuss was the previous day's Patient Advocate session. To her, the key point was to learn a key question that every provider should share with every patient once a year.
She briefly mentioned the one presentation from the day's General Session she was able to attend: analysis of the predictive value of VCTE.
00:19:53 - Philosophically important presentations
Louise discussed two sessions that delivered powerful, somewhat novel messages. The first was a symposium sponsored by Novo Nordisk about how SLD treatment could "manage the cardiometabolic side...rather than focusing on liver disease." The second was the "Healthy Livers, Healthy Lives" presentation which presented "very startling figures" about SLD impact on US healthcare costs and productivity and how and why India has targeted this disease aggressively.
00:26:29 - Building momentum and energy around AI
Louise and Roger both observed that momentum is building in MASLD and mentioned why they believe this is happening,
00:33:05 - Second conversation with Louise begins
Two days later, Louise and Roger conducted a second conversation, which focused on her enthusiasm for the updated Clinical Practice Guidelines and their practical implications.
00:36:12 - CPG session implications
Louise said this session had "blown her mind" with its forward-thinking style and recommendations. Her favorite point? The guidelines mentioned resmetirom even before it was approved in Europe.
00:44:07 - Thoughts about medications
Roger suggested that CPG aligned broadly with the drug presentations in the Late Breaker and General sessions. Collectively, those highlighted drugs with an array of modes of action and strengths across the metabolic continuum.
00:46:09 - Thoughts about devices
Roger asked whether Louise believed that, over time, the diagnostic focus would shift from liver stiffness and CAP to in-office PDFF. Louise discusses why this might be difficult.
00:51:48 - Conversation with Sven begins
This conversation, which took place 90 minutes after the final gavel, started with Sven praising the "vibrant hepatology community" evident at the meeting.
From there, the discussion covered the Clinical Practice Guidelines, major drug development presentations and other categories. The conversation is fairly short, but packed with information and insight.
01:06:42 - Question of the Week
Roger asks what kinds of support and education primary care will need to step into a leading role in treating SLD.
01:07:13 - Business Report
Plans for the next month, growth of the SurfingMASH Community, a special surprise instead of the Vault.
In this final conversation, Sober Livers leaders Jenn Jones and Beth Lehman share what they hope listeners will take from this discussion of HOPE (Healing Others with Peers and Education) and how they can help this unique support program grow.
The conversation starts with Roger asking what Sober Livers and/or transplant centers can do to help patients learn how to find a living donor. Beth says one key is to make "living liver" synonymous with transplantation, "as with donating a kidney, right?" Jenn adds that an individual who sought a live donor plans to help Sober Livers educate HOPE members on using social media more effectively. She adds that through HOPE, Sober Livers needs to make people who are less social media savvy aware of options and how to pursue them. Also, from a policy perspective, living donor surgery is considered elective for the donor. Until this changes, the process will be exceptionally expensive -- usually prohibitive -- for the donor.
In closing, Roger asked what issues the conversation missed. Beth asks that everyone remember the website soberlivers.org. Jenn comments that the organization does not yet have the funding it needs to expand during the first year. She notes that it is a 501(c)3 whose books are completely independent of the Fatty Liver Foundation and states that moving the program from Zoom to a more secure platform and covering all first-year expenses will cost $60,000. With that, the conversation ends.
Sober Livers leaders Jenn Jones and Beth Lehman join Roger Green to discuss HOPE, their new support community for people who have harmed themselves through AUD (Alcohol Use Disorder). This conversation focuses on plans and hopes for the future.
Roger starts this conversation by sharing a story from his own experience about the pressure caregivers struggle with and asks how HOPE (Healing Others with Peers and Education) will address caregivers and their needs. Beth acknowledges that this need is legitimate and that caregivers for these people may need a program of their own. The group wrestled with this issue when considering their original offering, but decided the organization needed to meet the needs of people living with this situation before offering services to caregivers. Jenn elaborates that the reason not to include caregivers in the initial group population is that it may limit the items and issues that HOPE's core constituency is willing to discuss. She says that creating a parallel caregiver program will be a pivotal next step once the target group is up and running.
Next, Roger asks what else Sober Livers would like to implement over time to enhance the program. Jenn notes that the organization plans to create benchmarks and conduct qualitative and quantitative research to ensure that “this is an effective community that’s actually helping people.” They will share this data and a resulting strategic plan with HOPE’s WHAC (Whole Health Advisory Council) and prospective sponsors, including one healthcare products company that has already committed to a starter grant.
In practical terms, Jenn mentions starting a second meeting at a different time of day, possibly one more suitable for West Coast residents with jobs. They plan to recruit transplant centers to make information available so that appropriate patients will enroll and even make initial contact during first hospitalization. They would like to educate the people living with disease on options they might not have considered and scientific advances. At one point, Beth mentions a desire for in-person meetings in cities with major transplantation centers.
In terms of education, Jenn mentions liver perfusion and finding a living donor as two areas Sober LIvers would like to provide support.
In this conversation, Society of Sober LIvers leaders Jenn Jones and Beth Lehman describe the HOPE (Healing Others with Peers and Education) program. They go on to discuss why version 1.0 does not include specific support for caregivers.
Jenn describes the program's core elements, starting with a monthly video call that is a support meeting one month and an educational program the next. The program will include a Facebook group where individuals can continue their conversations in private, plus a weekly blog and an array of educational resources. Beth adds that stopping drinking and addressing addictive behavior are not necessarily the same thing and that HOPE will help individuals address their overall behavior, not merely their AUD. Jenn adds that Sober Living is addressing issues holistically and anticipates that ideas and activities will "bubble up" from members. She also anticipates scaling up in time as interest grows.
Roger asks how a provider can help patients find their ways to Sober Livers and HOPE. Beth says the key is for the group to deliver educational materials to the offices where patients go. After Roger shares the group's e-mail address (soberlivers.org), Jenn notes that the Zoom address for the support meetings will not be publicly available. People must enroll to be invited. While enrolling on the Sober Livers website, they can learn more about the organization and its other resources.
This conversation focuses on the target population of patients with AUD (Alcohol Use Disorder) with decompensated cirrhosis and asks why this group needs a support community like HOPE (Healing Others with Peers and Education).
Roger asks what makes people who have harmed their bodies through AUD a unique community as compared to other communities providing support for people trying to change their behaviors. Beth and Jenn explain that the lifelong medical challenges associated with being post-transplant or living with cirrhosis create unique needs and challenges that traditional recovery programs do not address.
Roger describes a friend who was found on his bathroom floor vomiting blood and asks whether this person is a good candidate for the program. Jenn describes why that case is so serious and indicates the answer is "Yes." Beth adds that this person might not have addressed the behavior patterns that led him to overconsume alcohol, which would put him at risk of relapse and, therefore, in need of support.
This conversation re-introduces us to Sober Livers Founder/Visionary Jenn Jones and introduces us to Beth Lehman, Principal Strategic Advisor to Sober Livers and HOPE, a multi-element patient support program for people who have harmed their livers though AUD (Alcohol Use Disorder).
As this conversation starts, we meet Beth Lehman, Principal Strategic Advisor for Sober LIvers, who discusses her disease background and personal history and adds one thing we might not know about her otherwise.
After we meet Beth, Roger introduces the topic by discussing how the new nomenclature has broadened stakeholders' view of liver disease by incorporating AUD into the vision of steatotic liver disease through ALD and MetALD. In the aftermath of the new nomenclature uptake, Sober LIvers joined forces with the Fatty Liver Foundation and came to SurfingMASH's attention this way.
Jenn introduces HOPE, which stands for Healing Others with Peers and Education, an organization that provides peer support for people who have harmed their bodies due to AUD, while simultaneously advocating for "people to understand the disease better." Some peers will be living with cirrhosis, while others will be post-transplant. Patients may have other metabolic system issues.
After sharing how hard it was for her to confront her truth, Beth notes that while she has been involved in several different programs, none have had subgroups for people who harmed their bodies through AUD...which is why she believes this group is needed so badly.
Roger Green is joined by Sober Livers Founder/Visionary Jenn Jones and Principal Strategic Advisor Beth Lehman to discuss HOPE, a support program launching June 11 for people who have harmed their bodies through ALD and its consequences.
00:00:00 - Surf's Up: Season 5 Episode 18
Standard lead-in, including quotes from panelists
00:02:07 - Introduction
Roger describes the episode structure.
00:03:44 - Meet Beth Lehman
Beth Lehman, Principal Strategic Advisor for Sober LIvers, discusses her disease background and personal history,
00:08:45 - Groundbreaker
One good thing in the past week, personal or professional.
00:11:28 - Introducing HOPE
Roger starts the conversation by discussing how the new nomenclature has incorporated alcohol into the vision of steatotic liver disease. It was the new nomenclature that led Sober LIvers to link with the Fatty Liver Foundation.
Jenn introduces HOPE, (Healing Others with Peers and Education) an organization providing peer support for people living with active or remission Alcohol Use Disorder (AUD) while advocating for "people to understand the disease better." Peers will be living with cirrhosis or post-transplant.
Beth notes that while she has been involved in several different programs, none have had subgroups for people who harmed their bodies through consumption of alcohol...which is why she believes this group is needed so badly.
00:15:38 - Why patients who have harmed themselves have different needs
Roger asks what makes people who have harmed their bodies through alcohol abuse unique. Beth and Jenn explain that the lifelong medical challenges associated with being post-transplant or living with cirrhosis create unique needs and challenges.
Roger asks whether a friend who was found vomiting blood is a good candidate for the program. Jenn describes why the answer is "Yes." Beth adds that this person might not have addressed the behavior patterns that led him to overconsume alcohol, which would put him at risk of relapse.
00:22:22 - What the HOPE program includes
Jenn describes the program's core elements, starting with a monthly video call that is a support meeting one month and an educational program the next. Beth adds that HOPE's goal is to help individuals address their overall behavior, not merely their drinking. Jenn anticipates that ideas and activities will "bubble up" from members.
00:28:16 - Questions about providers and caregivers
Roger asks how a provider could help patients find their ways to Sober Livers and HOPE. Beth says the key is for the group to deliver educational materials to the offices where patients go. Jenn notes that the Zoom address for the support meetings is not publicly available. People must enroll to be invited. While enrolling, they can learn more about the organization and its other resources.
Roger asks about support for caregivers. Beth notes that Sober Livers plans to provide support over time, because "care partners are going through a lot." At the same time, she notes that people living with the disease may have things to say that they would not share with caregivers.
00:33:43 - Future plans, budget and wrap-up
Roger asks what else Sober Livers would like to implement over time to enhance the program. Jenn answers and then, In response to a question from Roger, estimates what it costs to run the program for a year. Sober Livers has raised some funds, but seeks more.
00:44:47 - Question of the Week
Roger asks listeners what other patient or stakeholder groups might benefit from a program like HOPE.
00:45:19 - Business report
The business report discusses SurfingMASH's EASL coverage, the high level of interest in the private community and the reason the vault is taking a week off.
This week's Vault looks back to the EASL Congress 2023 and includes Aleksander Krag, Sven Francque and all three surfers: Jörn Schattenberg, Louise Campbell and Roger Green. The focus of this conversation revolves around program design. The original conversation came with a robust description:
This conversation starts with Roger’s question to Sven around his role as Educational Councillor and the various educational opportunities embedded within the program. Sven first describes a postgraduate course that focuses on the link between NAFLD and cancer. He goes on to describe a plethora of activities which each embody different levels of education and participation for different stakeholder groups. Notably, he underscores the goal of broadening education to reach parties external to specialist hepatology groups. This is not only about raising awareness, but also engaging communities with the concept of liver health from a very young age. Roger asks what the balance is between virtual and onsite attendance and Aleksander suggests people are trending back to onsite participation. The group discusses why in-person attendance is especially positive for the previously described educational elements. From here Roger asks Aleksander and Sven for their lists of “3 things you can’t miss” for different participating groups. First, he asks what’s not to be missed for a recently minted transplant hepatologist. Next, he shifts focus to what’s not to be missed for attending students.
The conversation shifts to questions from Louise and Jörn which focus on how the program was put together. It becomes clear that this is a multifaceted event that combines the experiences of education, networking, science development and much more. Aleksander likens the meeting to a giant dinner party whereby the organizers are chefs who have taken a year to prepare an extravagant meal for thousands to enjoy. For the remainder of the session, Louise leans in on a comment Aleksander makes about allied health and points out that there are some very good and important sessions around health literacy.
This final conversation from SurfingMASH's EASL Congress 2024 preview includes two final papers, one covering MASLD drug development, and a diverse set of answers to Roger Green's closing question.
Jörn Schattenberg discusses a paper he will present on a completely new concept to treat MASLD, a Phase 2a trial of a transglutaminase inhibitor, a compound originally developed for Celiac disease. Aleksander Krag describes as "exciting" the idea that this concept came from Celiac disease.
Michelle Long discusses a late-breaker abstract, which means it is embargoed, and she cannot share many details. This is another "really good use" of a big data set, in this case data from an array of Novo Nordisk trials.
With all the abstracts presented, Roger Green observes that this is the first major Congress preview SurfingMASH has done where the discussion focused on anything other than drug development, in this case, data development.
Roger asks for a "big picture" lesson each panelist will leave Milano with. Michelle notes that while she likes Roger's comment about focus, she views Big Data development as driving a new, broader phase of drug development. The group agrees.
Beyond that, the panelists' closing comments vary in scope and focus but share themes that have emerged throughout the discussion.
This conversation revolves largely around two Big Data presentations Hannes Hagstrom's team is sharing at the EASL Congress. Every other panelist has at least one meaningful comment to make about the future of Big Data in MASLD.
Hannes describes two big data studies of his own, "very much Big Data, but it's not omics." One examined 860,000 residents of Stockholm who took a liver test between 2010-2022 seeking to estimate liver and cardiovascular risk. It relied on a tool from Stefano Romeo's group called the Fibrotic Mass Index. The results demonstrated the prediction of liver-related and cardiovascular-related outcomes.
The other study relied on the same dataset to build a prediction model for liver-related outcomes in the general population. Instead of relying on a dedicated test like FIB-4, which has false results on both sides, this assimilates five simple parameters (ALT, AST, GGT, ender, age) and proves to be far more accurate at risk assessment than FIB-4. The study team will also present a small, web-based calculator "where people can go to estimate the risk." The tricky part, Hannes notes, is where to set a tolerable risk threshold.
Jörn, thinking about the 860,000 sample, asks, "How much data is big enough?" Hannes notes that if the sample is big enough, we need not worry about statistical tests because we have true population-level data.
Michelle considers the overarching implications of Hannes's comments: "I think a risk-based view of this disease makes a lot of sense." Aleksander and Roger concur that using a risk-based screening approach is preferable, in large part because it should allow a far larger share of resources to be devoted to those with significant disease.
This conversation starts with Jörn Schattenberg joining the conversation. The main points are two abstracts, one reviewed by Jörn and the other by Aleksander Krag.
As Hannes finishes discussing his abstract, Jörn joins the podcast. While Michelle looks for an abstract she highlighted on which Jörn is an author, Jörn discusses a panel that Hannes will chair on the future of hepatology, at which Jörn will speak about artificial intelligence. Hannes shares his excitement about a session that looks to take a peak into the future, framing it in the context of the EASL vision and mission.
The abstract Michelle selects for Jörn is titled The cause of death, mortality rates and the role of sociodemographic risk factors and biomarkers in metabolic dysfunction-associated steatohepatitis in more than 18,000 real-world patients from the United States. Jörn shares the group's enthusiasm for large sample sets of "real-world" patients, this one obtained through the Optum health registry, and discusses some of the outputs of the research, notably including the association with EGFR and some "very nice" genetics aspects.
Roger asks the panel each to discuss one of their own abstracts they consider important. Aleksander describes a Galaxy consortium database of 900 people with a range of steatotic liver disease severity. The "true multi-omics" study incorporated "18 layers of omics" and also host genetic factors. He goes on to discuss the way the group dove into this massive set of data and how the results of this study and others like it will open a "new, new world of biomarkers." He describes the immense analytical needs for a data set with 900 cases and 18 layers of omics, which required analysis of "10 to the 11th power" to analyze." In the end, the data set identified 500 "highly significant" variables.
Jörn notes that while the data is extremely complex, it reaffirms the value of some of the pathways we have been studying. The challenge, Jörn notes, is to make it "easy" for the clinician. To Aleksander, "that's the thing...we need to bring" if studies like these are to become actionable. Roger comments that in complexity theory, complexity can produce simplicity if analysts do not seek too high a level of granularity. Aleksander sees the solution in creating tools based on host genetics, which are stable for life and which "everybody has."
This conversation starts and ends with thoughts from Michelle Long. Her first comment praises the expanded networking opportunities in the program, and her last comment focuses on the quality of the MASLD abstracts (really, all abstracts) and the importance of reviewing them in advance.
Michelle starts by commenting on the networking sessions that EASL is sponsoring around the large consortia and other projects. "It really speaks to how... open this community is to exploring different ideas and getting people together." She notes that these sessions have particular value for two groups: people just getting into the field and those looking for a potential collaborator. Aleksander describes these sessions as helping to support the big consortia by tying them into the networking sessions. It also demonstrates the way that academia, companies and public funders align on pivotal projects.
Roger comments that this is consistent with the generally high level of collegiality he sees in the hepatology community. In response, Aleksander states that the meeting will revisit EASL's mission and vision, which speaks to the many ways the organization can advance liver care.
Roger asks Michelle what else she anticipates eagerly about the Congress. Her reply? "Don't sleep on the abstracts." She starts reviewing the abstract book and quickly highlights 75 of interest, and then states there are far more than just those 75 that have high-level value. She notes that our fellow day Surfers, Aleksander, Hannes and Jörn, are authors of some of these. She describes the themes of linking and collaboration as coming through the abstracts. Finally, she recommends poster sessions as a place to dig into what lies behind the document for some pivotal pieces of research.
Roger invites Michelle to choose one abstract from her 75 with Aleksander, Hannes and Jörn as authors so that the three can describe their work.
The first abstract Michelle highlights has Aleksander as an author and is titled Longitudinal changes in liver stiffness measurements in a population-based screening cohort of 5,517 participants. Without revealing conclusions or interpretations, Aleksander describes the work his group did and then shifts focus to advocate that all listeners and attendees review abstracts extensively before coming to the meeting.
The second abstract Michelle highlights has Hannes as an author and is titled The validation of the Baveno Rule of 5 in a real-life multicenter cohort of patients with metabolic dysfunction-associated steatotic liver disease. Like Aleksander, Hannes does not share data, but discusses how valuable a multicenter cohort can be in answering pivotal questions as compared to single-sample studies, "which cannot be replicated elsewhere."
This first conversation from our EASL Congress 2024 preview starts with EASL Secretary General Aleksander Krag offering his vision for next week's meeting in Milano, after which Hannes Hagstrom shares some of his thoughts about the meeting design.
Aleksander starts by discussing the preparation that has gone into this Congress since the Vienna meeting closed last August. The goals are ambitious, but he feels EASL has, by and large, succeeded. Aleksander mentions that 7,000+ people have registered, including 80+ companies and 25+ patient groups. and that researchers submitted 3,000 abstracts, 2,000 of which have been accepted. "Almost 300 different types of sessions" with 450 faculty members focus on:
- The one approved MASLD drug and nine others in late-stage development, including "several Phase 2 studies"
- Breakthroughs on non-invasive tests
- An update on the "one-year baby" nomenclature, including a look at alcohol in the context of ALD and MetALD
- Enhanced understanding of the underlying disease.
He also highlights the EASL Studio as a "relaxed" place to listen to important discussions. Finally, he praises Milan's charms, particularly its food and wine.
Hannes describes the scale of the program as "like going to a place with a lot of good restaurants, but you only have one stomach," with not only research presentation sessions but also an array of meetings. He also commends the design element that places young researchers in prominent positions. Aleksander notes that some choices of chairs and events are designed specifically to move the public dialogue beyond "the usual suspects."
Next week, 7,000+ hepatology stakeholders will convene in Milano, Italy, to consume 2,000+ posters and presentations, including an extensive set of MASLD studies, at EASL Congress 2024. EASL Secretary General Aleksander Krag, Hannes Hagstrom, and Michelle Long join Jörn Schattenberg and Roger Green to preview the program.
00:00:00 - Surf's Up: Season 5 Episode 17
Standard lead-in, including quotes from panelists.
00:02:40 - Introduction
Roger describes the structure of this episode.
00:04:21 - Groundbreaker
Good personal and professional news from the panelists.
00:08:04 - A 10,000m look at the EASL Congress 2024
Aleksander discusses the preparation that has gone into this Congress, resulting in 2,000 accepted abstracts presented in "almost 300 different types of sessions" from 450 faculty members. Many focus on the range of key MASLD issues.
Hannes commends the design, which prominently positions young researchers.
Michelle says the networking sessions that EASL is sponsoring around the large consortia and other projects " really speak to how open this community is to exploring different ideas and getting people together."
00:21:01 - Michelle praises abstract quality and selects abstracts for colleagues to review
Michelle advises, "Don't sleep on the abstracts;" she quickly highlighted 75 of interest. She recommends poster sessions as a place to dig into what lies behind some pivotal pieces of research.
Roger invites Michelle to choose one abstract from her 75 that have her fellow panelists as authors, so that the three can describe their work.
Aleksander and Hannes both choose to describe the work their groups did on the various abstracts, but both describe methods and overall benefits.
00:26:41 - Jörn Schattenberg joins panel
As Hannes makes his statement, Jörn joins the podcast. He starts by discussing a panel Hannes will chair on the future of hepatology at which Jörn's will focus on AI. Hannes shares his excitement about a session that looks to take a peak into the future.
Jörn describes the abstract Michelle selects for him as a Big Data study of "real-world" U.S. patients, which he sees as having great benefit compared to looking at the patients he treats.
00:30:25 - Panelists each choose an abstract to discuss
Roger asks each panelist to discuss an abstract. Aleksander and Hannes each describe Big Data studies, but these are quite different. Aleksander's relies on massive computing power to analyze 12 levels of omics data for 900 patients, while Hannes's two are based on 860,000 residents of Stockholm who received a liver test between 2010 and 2022.
One study from Hannes demonstrated that five simple parameters proved far more accurate than FIB-4 in assessing risk. To MIchelle, "a risk-based view of this disease makes a lot of sense." Aleksander and Roger concur that such an approach will probably yield a far more efficient use of resources.
Jörn discusses a drug development paper reporting on a Phase 2a trial of a transglutaminase inhibitor. Michelle mentions an embargoed late breaker abstract that she describes as a "really good use" of a big data set from an array of Novo Nordisk trials.
00:48:31 - Closing comments and wrap-ups to discuss
Roger asks each panelist for a "big picture" lesson they will take from Milano. Closing comments from the panelists vary in scope and focus but share themes that have emerged throughout the discussion.
00:54:55 - Question of the Week
This week's question of the week asks which sources of insight will drive the next generation of MASLD research.
00:55:44 - Business Report
This week's news on how SurfingMASH will cover the EASL Congress, our new private community, some of its new features and a description of the vault episode.
In this excerpt from last July, Stephen Harrison shares results of the FASCINATE-2 study as part of SurfingMASH's larger coverage of exciting drug trials presented at The EASL Congress.
The original writeup reads:
This month, Surfing NASH embarks on a series of episodes dedicated to takeaways emerging from June's two major conferences: the 2023 EASL Congress in Vienna and the American Diabetes Association's 83rd Scientific Sessions *meeting in San Diego. This is the second session focusing on drug development, and specifically, on several presentations for exciting drugs in development. In doing so, the Big Band of Surfers (Stephen Harrison, Jörn Schattenberg, Louise Campbell and Roger Green) are joined by Mazen Noureddin for a fascinating conversation which covers plenty of compelling clinical trial data.
Jörn preludes this discussion by noting just how much important drug development research was released at this year's EASL Congress. Stephen proceeds from here to detail positive Phase 2b FASCINATE-2 clinical trial interim data for fatty acid synthase (FASN) inhibitor, denifanstat, as presented at EASL Congress by Rohit Loomba. In the process, Stephen elucidates why the idea of a FASN inhibitor is so exciting. It blocks de novo lipogenesis, which means it can have effects on inflammation and possibly direct fibrosis inhibition. Previously in Season 4, Episode 32, it was discussed why inflammation, which is tied to liver volume, might be a critical component to better understand for therapuetic development and the wider scope of liver health. From here, Stephen goes on to describe the trial, starting with basic design and sharing the MRI-PDFF and biomarker data that was presented at the EASL Congress. He finishes with safety and efficacy data and a general comment that the trial demonstrated, 'the drug is doing what it's intended.'*
This is the second half of Roger Green's conversation with Dimitar Tonev. It focuses largely on some of the elements of Stephen's personality that made him so unique and a role model within the community.
Dimitar discusses one more innovation Stephen brought to MASLD clinical trials: recruiting in neighborhoods that received lower levels of medical care and then, within those communities, recruiting within families. Roger harkens back to the recruitment issue to tell the story that Stephen and he started SurfingMASH to educate sponsors and sites about the ability to keep trials running in a site network like Summit.
To Dimitar, one thing that made Stephen special was his "enormous capacity to work long hours," to the degree that left Dim "wondering how this is even humanly possible." He mentions early clinic starts, 4 a.m. text messages, and other related of-hours items. Roger shares a story he heard at the funeral about Stephen stating that he didn't sleep much but slept"very efficiently." Dimitar and Roger agree about the energy and enthusiasm Stephen devoted to everything he did.
Dimitar tells a story about Stephen flying over the Atlantic with his family. You'll have to listen to learn it. He goes on to discuss Stephen's passion for working on minor diseases that were unlikely to ever pay off in terms of money or prestige and, finally, how Stephen boosted Dim's self-image by presenting a couple of Dim's slides during a presentation at a major meeting.
The conversation shares the first half of Roger Green's interview with Dimitar Tonev, whose tribute comment to Stephen Roger shared in a recent SurfingMASH weekly newsletter.
Because this is Dimitar's first appearance on SurfingMASH, he starts by telling the audience a bit about his history, including the fact that he came to know Stephen from the viral hepatitis days. As his "one unique thing," Dimitar mentions his proficiency as a skier, which leads Roger to ask about his description of Stephen in the SurfingMASH note as a "clumsy skier." Dim states that Stephen's form wasn't the best but that he skied with energy and passion. He goes on to tell a different story about how he broke Stephen's glasses the first time they met and how Stephen was able to laugh about it with him.
Dimitar describes the "really impressive way" Stephen developed his process for recruiting patients into what were then called NASH studies through the "first iterations of Summit," the idea of a site network. In response to a question from me, he described the pre-screening pathway as one element of the "secret sauce," and the use of portable FibroScan devices as another. He goes on to describe that Stephen's sites could recruit 8x as many patients per month as a typical CRO, which is why the Summit network has become a preferred provider to many CROs and why no one has yet been able to replicate his success.
This conversation includes the second half of Jörn Schattenberg's and Roger Green's interview with Donna Cryer. It focuses largely on Stephen's inclusive approaches towards bringing stakeholders to pivotal discussions.
Donna starts this conversation by noting an important thing she learned early in her career: when patients, advocates and physicians work together, their collective power is far more than the sum of their individual impacts. She commends Stephen as one KOL who always made certain that patient voices (including Donna's) and organizations had seats and voices at the table. She says, "I will be forever grateful for all the times he held space..." to that Donna and other patients/advocates could be involved in a major discussion.
Jörn concurs and notes that this podcast was a key element in sharing different stakeholders' perspectives throughout the entire MASLD community, particularly during the COVID-19 pandemic when meetings were held virtually. Finally, Roger notes that Stephen sought to include allied health providers the same way Donna describes him including patients and advocates.
When Roger asked for "Harrisonisms", Donna does not offer a specific one. Roger recalls Stephen's surprise that Roger knew the meaning of the phrase "Hoddy Toddy" to Ole Miss grads and how he quickly integrated phrases of others into his own conversations and presentations. WIth that, the interview ends.
This conversation includes the first half of Jörn Schattenberg's and Roger Green's interview with Donna Cryer. While the question is about Stephen's most outstanding contribution to MASLD, the focus is more on his remarkable ability to trigger increased awareness of MASH in many different ways.
Roger starts the conversation by asking Jörn and Donna to describe one outstanding contribution (okay, maybe two) that Stephen made to the field of MASLD. Jörn talks about Stephen's role as integrator, talking to all different kinds of players, designing trials, focusing on issues and needs of patients, regulators, investors. To Jörn, Stephen was "a lens focusing that something that was needed to spark the fire..." Picking up on this insight, Roger asks specifically about Stephen's role in the founding of NAIL-NIT (along with Mazen Noureddin). Jörn harkens back to Stephen's earlier work on the LITMUS Cohort Study and contributions to the field to describe the process that led him and Mazen to start NAIL-NIT, and notes the consortium's tremendous success to date.
Continuing this theme, Donna describes Stephen's ability to bring people together and his providing "unique space for having smaller, intimate conversations: when necessary. She cites NASH-TAG, another event he co-founded, as a meeting designed specifically for this purpose and a remarkably fertile place for making progress on big issues.
Roger recalls Stephen bringing Donna to the early podcast to describe International NASH Day 2021, and goes on to comment that Stephen was the rare individual who embodied Malcolm Gladwell's three legs of the Social Virus stool: scientist, innovator and salesman. Although he doesn't say so in the interview, the implication is that Stephen's ability to play all these roles at once has sped the social awareness of MASLD and MASH and the efforts to advance solutions.
Finally, Roger recalls Stephen becoming "ticked" during an early SurfingMASH episode on the FDA's first Complete Response Letter for obeticholic acid as proof of his passion for the work.
Global Liver Institute Founder and CEO Donna Cryer and hepatology researcher and industry executive Dimitar Tonev join Jörn Schattenberg and Roger Green to share memories of our co-founder and MASLD leader Stephen Harrison.
00:00:00 - Surf's Up: Season 5 Episode 16
Standard lead-in, including quotes from panelists
00:02:55 - Introduction
Roger describes the structure of this episode.
00:04:04 - Conversation with Donna and Jörn, including groundbreakers
Good personal and professional news from Donna, Jörn and Roger.
00:07:32 - Stephen's most outstanding contribution to MASLD
In response to Roger's question, Jörn describes the breadth of Stephen's contributions and interests. To Jörn, Stephen was "a lens focusing that something that was needed to spark the fire." Roger asks him to discuss Stephen's role in founding NAIL-NIT. Jörn's answer covers Stephen's earlier work on the LITMUS Cohort Study and other contributions to the field as well as NAIL-NIT.
00:10:34 - Personal notes about Stephen
Donna continues this theme by speaking to Stephen's ability to bring people together and his providing "unique space for having smaller, intimate conversations: when necessary.
Roger talks about Stephen bringing Donna to the early podcast to describe International NASH Day 2021 and comments that Stephen was the rare individual who embodied Malcolm Gladwell's three legs of the Social Virus stool.
00:14:33 - Stephen's advocacy of patient advocates and allied providers
Donna discusses having learned early in her career about the synergistic power of patients, advocates and physicians. She commends Stephen as one KOL who always made certain that patient advocates and organizations had seats and voices at the table,
00:19:06 - "Harrisonisms" and Harrison stories
Donna did not have Harrisonisms. Roger recalled Stephen's surprise that Roger knew the meaning of the phrase "Hoddy Toddy" and how he quickly integrated phrases of others. WIth that, the interview ends.
00:21:39 - Meet Dimitar Tonev
Dimitar starts off by telling the audience a bit about his history. His "one unique thing" is about his competence as a skier. This leads Roger to ask about his description in the SurfingMASH note of a "clumsy skier." Dim states that Stephen's form wasn't the best but that he skied with energy and passion. He goes on to tell a story about breaking Stephen's glasses the first time they met and how Stephen was able to laugh about it with him.
00:26:41 - Stephen's visionary approach to trial recruitment
Dimitar describes how Stephen developed his process for recruiting patients into what were then called NASH studies through the "first iterations of Summit," the idea of a site network.
00:31:19 - Another Harrison innovation
Dim discusses one more innovation: recruiting in neighborhoods that received lower levels of medical care and then recruiting within families. Roger shares that this podcast started to educate sponsors and researchers about the ability to keep trials running in a site network like Summit.
00:34:35 - What made Stephen Special and Wrap-Up
To Dim, Stephen special was his in his "enormous capacity to work long hours," Dim and Roger agree about the energy and enthusiasm Stephen devoted to everything he did.
00:37:48 - Special Stephen stories
Dim tells a story about Stephen flying over the Atlantic with his family. You'll have to listen to learn it. He goes on share two more special stories about Stephen. .
00:43:29 -Question of the Week
Roger asks listeners who attended DDW last weekend which paper or presentation struck them most forcefully, and why.
00:44:02 - Business report
This week's news on the Stephen Harrison memorial, our new private membership list, upcoming episodes, and listener updates.
This week's vault looks back to SurfingMASH's Barcelona coverage in earlier years to identify one point we can use to evaulate progress in the field. In this case, we looked back one year to see that INCBCN focus on NITs was driven largely by work from NAIL-NIT.
Specifically, the 2023 version of NIT coverage at #SLDThinkTank 2024 was a discussion of real-world data from NAIL-NIT. The original conversation has a robust description:
Surfing NASH returns to review the 2023 Innovations in NAFLD Care Workshop (INCBCN) which concluded on 27 May in Barcelona. Conference founders and directors Jeff Lazarus and Jörn Schattenberg discuss highlights and takeaways of the event with Louise Campbell and Roger Green.
This conversation captures the meeting in a broad sense by outlining its goals and reason for being. Jeff describes this year’s emphasis on expanding the community of practice beyond hepatology. For example, friend of the podcast and co-host of our Rising Tide series, Ken Cusi, chaired a session on the role of endocrinology and diabetology in the early diagnosis and management of NASH. In Jeff’s words, “We were trying to look at the liver more holistically and look at who else should be involved in a multidisciplinary approach.”
The discussion shifts to a review of the NASH-NITs Real-World-Evidence Summit. Jörn suggests that moving forward, the Summit ought to be expanded and broadened. After Jörn comments on the positive experience of facilitating hands-on engagement, Louise offers her take. She underscores that FibroScan testing requires adequate knowledge and training to be well-executed with precision. The group goes on to describe in detail what made the Summit unique and how it might grow in the future.
This wrap-up conversation focuses on elements to add and reconsider for #SLDThinkTank 2025. One key concept was to broaden the set of stakeholders invited to participate. Another involved focusing on the broader idea of "preventive hepatology."
This conversation starts with Roger Green asking the group what other topics from #SLDThinkTank 2024 the panel should discuss before closing. Jörn Schattenberg expresses the hope that future meetings will have a wider representation of patient advocates and allied health professionals. Jeff wishes a representative of WHO could have been there. Mike recommends broadening primary care presence, and Maja would like to see more on technologies, specifically citing proteomics and mass spectrometry as two examples. "As an outsider," Louise asks whether it is time to focus more intently on preventive hepatology and pre-screening. Jeff elaborates on the concept of preventive hepatology, anticipates that pre-screening will come from other specialties and notes that advocates and practitioners are focusing on preventive hepatology concepts without using that phrase.
Finally, Roger asks the group how non-practitioners can help drive wider awareness and action. Group answers vary widely.
This conversation from #SLDThinkTank 2024 focuses largely on ways to improve delivery of screening services to patients. Along the way, participants reflect on the value of having Rezdiffra approved in the US and on its way to approval in other markets.
As the conversation starts, Mike Betel transitions from a broader discussion of prevention to note that there are 94 FibroScan devices for all of Canada. Even these 94 are severely underutilized! Maja Thiele states that having a drug in market will motivate stakeholders throughout the system to screen more aggressively because they feel having an approved drug will enable them to help patients better. Louise Campbell asks whether the vision around utilizing FibroScan better included more creative approaches to site of delivery. This leads the group to discuss what will be necessary to improve utilization of these machines. Specifically, Mike asks who will coach allied health providers and physicians to use NITs (specifically scanners) as a way to open broader conversations on liver health.
Jeff says that the last few minutes of discussion provided a general flavor of what the Open Space session was like. and comments on why this kind of small meeting is the right design for thinking big and brainstorming openly. He notes the mandate to get "better bang for the buck." Mike says it was extremely helpful to have a large number of younger attendees.
As the Surfers dive deeper into the substance of #SLDThinkTank 2024, Jeff Lazarus describes the meeting agenda and anticipated outputs, and other panelists discuss how the "Magic Wand" exercise and other ideation elements produced some truly "Big Picture" insights.
The conversation starts with Roger asking participants to describe the meeting agenda and what they considered its highlights. Before describing the agenda, Jeff enumerates the paper(s) that will result from this meeting. He lists the ten major issues the group developed for the pursuit of ending MASLD and MASH as a global health threat and proceeds to describe and elaborate on several of these.
When Jeff finishes, Jörn recalls that at the end of the first session, the chairs gave participants a "Magic Wand" to achieve the broader goal of making dramatic progress in patient screening and treatment. He notes a consensus that "we ha[ve] mechanisms and biomarkers" but have major social, political and academic challenges ahead if we are to slow the rate of the pandemic meaningfully. To Jörn, the field may need to improve tests and clarify cutoffs, but the major issues require support from governments and payers paying for tests rather than asking patients to pay for their own. Maja notes how long and challenging "the road between research finding and then implementation" is. Mike and Jeff go on to focus on prevention issues as separate from treatment.
The first conversation from our #SLDThinkTank 2024 coverage explores the meeting design from two perspectives. Co-hosts Jeff Lazarus and Jörn Schattenberg discuss the overall design, after which participants Maja Thiele and Mike Betel share their reactions.
The conversation starts with Jeff providing background and rationale for the #SLDThinkTank 2024 design. He starts by referring back to an initial meeting in 2019 and the first two years of INCBCN (Season 4, Episodes 13, 23; Season 3, Episodes 18, 24). He then describes why he felt a small-group brainstorming approach might work better than the last two years of PowerPoint presentations and group questions. This agenda, which was designed to encourage dialogue that generated new answers to the largest questions in SLD, included five "hot topic" sections, two focused workshops and an innovative ideation concept called Open Spaces.
When Jeff finishes, Jörn describes how the highly innovative "Open Spaces" element actually worked in his section of the room.
Maja and Mike share their impressions of the meeting. Maja starts by praising the Open Space concept, which she describes as "especially fruitful" due to the diversity of attendees. After Mike seconds her comment about diversity, she goes on to describe what she did during Open Spaces. The rest of the group chimes in with points about the design.
SLDThinkTank participant Maja Thiele, a first-time guest, shares her professional history and the traditional "one thing the audience might not know about you if you did not tell them." In the process, she talks about her professional history and a current study, LiverAIM, for which she is leading a pivotal element.
Two elements make this introduction unique. First, Maja's "One Thing" answer is a first among the 120+ guests that have appeared on this podcast. She is the first SurfingMASH guest who has actually served as a radio host (old podcasters like Roger live with awe and respect for radio hosts!) Second, Jörn Schattenberg asks her to discuss her pivotal role in LiverAIM, the largest randomized control trial ever anticipated in SLD.
This episode provides not only an excellent understanding of a first-time panelist we hope will join us often in the future, but also an introduction to LiverAIM, a study that will likely be the focus of many SurfingMASH episodes in years to come.
SLDThinkTank 2024 co-chair Jörn Schattenberg and SLD Think Tank co-chair Jeff Lazarus, participants Maja Thiele and Mike Betel and SurfingMASH co-hosts Louise Campbell and Roger Green convene to discuss #SLDThinkTank, a conference designed to innovate solutions for addressing large issues, many involving public health, in conquering MASLD.
00:00:00 - Surf's Up: Season 5 Episode 15
Standard lead-in, including brief quotes taken directly from the episode.
00:02:45 - Introduction
Opening comments discussing the aggressive travel schedules of our guests.
00:04:02 - Meeting Maja Thiele and LiverAIM
Maja introduces herself to our audience, including her "One Fact:" she has been a radio host in Denmark. Jörn mentions that Maja is about to start "the biggest randomized controlled trial in hepatology" through LiverAIM, an extremely ambitious project funded through the EU Innovative Health Initiative.
00:12:47 - Groundbreaker
Each panelist shares one piece of good news from the previous week.
00:15:38 - #SLD ThinkTank 2024 design
Jeff provides background and rationale for the #SLDThinkTank 2024 design, going back to an initial meeting in 2019 and the first two years of INCBCN (S4, E13 and E23; S3, E18 and E 24). The event included five sections, two workshops and an innovative concept called Open Spaces. Jörn provides color about how Open Spaces actually worked.
00:20:13 - Participants' experiences
Maja praises Open Spaces, which she describes as "especially fruitful" due to the diversity of attendees. After Mike seconds this comment, she describes her Open Spaces experience.
00:25:53 - Meeting highlights
Roger asks participants to describe their highlights from the meeting. Jeff describes the paper(s) that will result from this meeting, lists the ten major issues the group developed for ending the SLD pandemic, after which he elaborates on a few of these.
00:29:40 - The Magic Wand exercise
Jörn: at the end of the first session, chairs gave participants a "Magic Wand" to achieve their goals. He notes a consensus that "we ha[ve] mechanisms and biomarkers," but face major public and policy challenges if we are to slow the MASLD growth rate meaningfully. Maja notes the long timeline from research to implementation.
00:33:09 - Improving utilization
Mike discusses prevention separate from treatment: There are only 94 FibroScan devices in Canada, and even these are underutilized. The group discusses what will be necessary to improve scanner use in a future world where having medicines motivates medical stakeholders.
To Jeff, this discussion provided a sense of how the Open Space session worked and why this is the right design for big issues like "getting better bang for the buck."
00:43:59 - NIT Summit
Jörn discusses the NIT Summit, which preceded the #SLDThinkTank. He sees this as a first step toward acknowledging that we need to train more people and find ways to train them better. Jeff agrees.
Maya describes Elliott Tapper's state-of-the-art talk on social media. Her takeaway: video is a valuable new format, especially for younger stakeholders.
00:47:39 - Wrap-Up Questions
Roger asks the group what other topics from #SLDThinkTank 2024 to discuss before closing. No two panelists' answers are redundant. Finally, Roger asks how non-practitioners can help drive wider awareness and action. Again, answers vary widely.
00:55:45 - Question of the Week
Roger asks listeners to describe "one way that making better use of the tools we have today (diagnostics and medicines) can make a major dent in the MASLD pandemic."
00:56:38 - Business section
This week's news on increasing interest in SurfingMASH, our first newsletter, the Stephen Harrison Memorial page, upcoming episodes and this week's Vault.
SurfingMASH's last year-end interview with Stephen Harrison took place in 2022. Louise Campbell and Roger Green join Stephen to discuss a promising year in MASH drug development and the podcast itself.
At the time, this was the description of the interview posted in Buzzsprout:
In the Season 3 NAFLD Year-in-Review conversations series, Surfers Jörn Schattenberg, Louise Campbell and Roger Green embark on a string of interviews with a handful of Key Opinion Leaders who made headlines and advances in Fatty Liver disease in 2022. In this exclusive segment, podcast co-founder and former co-host, Stephen Harrison, joins Louise and Roger to discuss the year-in-review as recorded before Madrigal’s breaking announcement of the Phase 3 MAESTRO-NASH results last week.
From the outset, Stephen admits there were “a lot of pleasant surprises” this year, alluding to the multiple positive Phase 2 trial results among other recent press releases. He anticipates several exciting modes of action becoming available in the imminent future. The interview goes on to look at advancements made in methodology of interpreting liver biopsies, understanding the limitations of biopsy and degrees of mitigation in response to those shortcomings. Stephen also offers in-depth investigation into the uptake of NITs as conditional clinical trial endpoints, something he sees as a process whose momentum keeps growing and strengthening.
Throughout this session, Stephen provides speculation as to what the promising new year holds for the Fatty Liver field. In his words, 2022 revealed “the most incremental advances in the field of NASH in the past decade.” He adds that, like this year, 2023 is primed to be pivotal. Surf on for the full-length, insight-laden interview with a remarkable physician and Principal Investigator making tremendous contributions to the pursuit of putting a major dent in Fatty Liver.
Manal Abdelmalek and Naim Alkhouri join co-hosts Jörn Schattenberg, Louise Campbell and Roger Green to reflect on the greatest professional accomplishments of co-founder and former co-host Dr. Stephen Harrison.
Naim Alkhouri starts this conversation by describing the two prospective epidemiology papers Stephen co-authored at San Antonio Military Medical Center in 2011 and 2021, an innovative design that provided early estimates of the breadth of MASLD and MASH in an asymptomatic population. He goes on to discuss Stephen's work on FAST and other NITs and finishes by remembering Stephen's exceptional work in drug development, culminating in the recent FDA approval of Rezdiffra.
Manal Abdelmalek starts her comments by recalling that Stephen developed the BARD score and, years later, celebrated that it had been supplanted by better tests. After commenting on his impact in drug development, she describes him as "visionary" and says Stephen was "not a one man show. He thought about networks and collaborations and how to move a field forward with speed and agility."
Louise Campbell also reflects back on the BARD score and the process by which Stephen came to accept that the nomenclature change was a necessary thing. She closes her comments by reflecting on his persistence and innovation in drug development and finishes with a Harrisonisms about the value of failure and learning in the development of the product WD-40.
Finally, Roger Green discusses how Stephen's desire to tear apart his failures and learn from them resulted in the landmark paper that challenged how biopsies were being read and interpreted in clinical trial design, and also agrees with an earlier comment from Manal about how innovative the original design for Pinnacle Clinical Research was.
Manal Abdelmalek and Naim Alkhouri join co-hosts Jörn Schattenberg, Louise Campbell and Roger Green to share personal memories of co-founder and former co-host Dr. Stephen Harrison.
Naim Alkhouri starts the conversation by describing how he met his "friend and mentor," Stephen. He recalls coming to San Antonio in 2017 to work with a different research group and contacting Stephen. Stephen told Naim he had "made the wrong decision" by not joining his team instead. Nonetheless, Naim persisted, and the two began a rich, rewarding friendship and research experience, which Naim describes in greater detail.
Jörn Schattenberg says that Naim's story resonates with him. Stephen "support[ed] younger people in the field," including Jörn when he was starting his career in Germany. Historically, there had been challenges in conducting clinical trials in Germany, but Stephen worked with Jörn to overcome these and create a stable structure and base for conducting MASH trials. Jörn notes that the relationship Naim described applies not only to the two of them, but also to many other young researchers.
Manal Abdelmalek recalls meeting Stephen in the earliest days of MASH, when a few young researchers shared posters in a "dark corner" of an AASLD meeting. Manal was impressed by Stephen's energy, warmth, curiosity and confidence that what was then called NAFLD would be "big" someday.
Louise Campbell recalls meeting Stephen in the early days of SurfingMASH and always being appreciative of his support for nurses and allied professionals and the role they play in patient treatment. She goes on to note that the SurfingMASH podcast's growth affirmed the vision that Stephen and Roger Green had when they started the podcast.
Finally, Roger Green shares his story of meeting Stephen at NASH-TAG 2019 and being impressed with how his energy suffused the entire space. Roger goes on to describe the process by which he and Stephen started the podcast and decided to expand its scope.
Manal Abdelmalek and Naim Alkhouri join co-hosts Jörn Schattenberg, Louise Campbell and Roger Green to rshare some of their favorite "Harrisonisms" - words, phrases and verbal memes associated with co-founder and former co-host Dr. Stephen Harrison.
Naim Alkhouri starts by stating two of his favorite Harrisonisms, two that SurfingMASH listeners know well: "is the juice worth the squeeze?" and "Keep It Simple, Stupid." He goes on to add one that never appeared on the podcast, "FAIL stands for First Attempt In Learning," which he used frequently in discussed failed clinical trials.
Manal Abdelmalek shares several phrases she describes as "words to live by." Two of these are "don't you don't take yourself too seriously " and "There will be failures. The worst ones possible are those that you don't grow and learn from." She discusses how human, approachable and down-to-earth Stephen was, and closes with a story about him ordering a hamburger and "American French Fries" at a gourmet restaurant in Paris because that was all he really wanted to eat.
Louise Campbell shared a Harrisonism she heard for the first time at Stephen's funeral about the difference between wisdom and knowledge: "Wisdom was knowing that a tomato was a fruit, and knowledge was knowing not to put it in a fruit salad." She goes on to comment on the joy he took in living a life of service.
Finally, Roger adds two favorites of his own: "the liver is the canary in the coal mine," and that when Roger heard Stephen ask whether the juice was worth the squeeze, he always followed it with "is the view worth the climb?" Roger goes on to tell a story about Stephen's older brother, Ken, responding personally to every social media post-mortem to Stephen he could find because it is what Stephen would have done, and Ken's comment about Stephen's basic humility and dedicating his accomplishments to "God's glory."
Finally, Naim tells about story about Stephen's interest in wine and Naim's in shopping and how they merged in a single vignette about Stephen and his daughter Anna Lauren in Paris.
The sudden passing on April 23 of our co-founder and colleague Stephen Harrison sent shock waves throughout the global SLD community. This week, Manal Abdelmalek and Naim Alkhouri join Jörn Schattenberg, Louise Campbell and Roger Green to remember and pay tribute to an exceptional leader, role model and human being.
00:00:00 - Surf's Up: Season 5 Episode 14
Episode introduction, including brief quotes taken directly from panelists.
00:03:11 - Introduction
Roger introduces the podcast. The three key opinion leaders, Jörn Schattenberg, Manal Abdelmalek and Naim Alkhouri, discuss their fast-paced, high intensity travel schedules.
00:04:41 - Groundbreaker: a special memory of Stephen
In place of a traditional SurfingMASH groundbreaker, Roger asks each panelist to share a special memory of Stephen. In turn, panelists discuss how they got to know Stephen and/or the role he has played in their lives. Summaries cannot do the emotion of these recollections justice.
00:17:30 - One Harrison accomplishment
Roger asks the group each to describe an accomplishment that Stephen has left the field. Each panelists provided at least 2 or 3, with no redundancy.
00:23:52 - "Harrisonisms" and wrap-up
In closing, Roger asks panelists each to provide a favorite "Harrisonism." Answers varied, although every group member recalled Stephen's question, "Is the juice worth the squeeze."
00:33:33 - Question of the Week
Roger asks how listeners feel their lives or work were affected by Stephen Harrison, either directly or indirectly.
00:33:56 - Business Report
This week's news on our new newsletter, future conversations, and the Vault, plus more on how we plan to honor Stephen.
This vault conversation looks back to our coverage of International NASHDay 2023, the predecessor title to this year's Global Fatty Liver Day.
Thursday, June 8 was International #NASHDay 2023 and the podcast hosted a special session featuring patient advocates Gina Villiotti Madison (NASH kNOWledge), Marko Korenjak (European Liver Patients' Association) and Michael Betel (Fatty Liver Alliance*). With co-hosts Louise Campbell and Roger Green, the group shares both a positive and sobering discussion around the Fatty Liver public health epidemic and its impact on younger generations now and into the imminent future.
Roger starts this conversation by asking Louise to provide more information about the U.K. Parliament debate that had just commenced. Louise notes that MPs from all parts of the UK participated and that they were extremely well-informed on childhood NAFLD and other issues. She notes that members told stories of their own weight loss and government promise to brief MPs on liver disease on an interim basis going forward. One MP said he did not like the term living with obesity, which is considered patient sensitive, because it implies that obesity is a permanent condition. This leads to Roger's closing question which asks each panelist to envision what their organizations' key 2024 International #NASHDay activities might be. While their answer are aligned with what they did for the International #NASHDay 2023, listen for some different twists and new directions.
This is a particularly important and moving episode that captures a range of topics pertinent to the patient perspective and, more broadly, stepping up to NASH.*
This closing conversation introduces two new concepts: the idea that MASH has so many facets that it is comparable to the metaphor of blind people touching an elephant, and the provider mandate to "rule the liver out" when assessing patients with metabolic diseases.
Roger cites the parable of the blind people touching the elephant as a metaphor for liver disease, which is a precursor for multiple seemingly unrelated diseases (cardiovascular and extra-hepatic cancers, to name two). He says the point is to teach liver disease to healthcare professionals as "the elephant," not its different parts. Louise agrees and suggests that the simple action point for liver disease-as-elephant is to "rule the liver out" when assessing the various related diseases. The test for this must be "cheap" and "accessible;" it does not exist anywhere in the world today.
Roger suggests that the "Keep It Simple, Stupid" approach to liver disease incorporate the two simple action items discussed in this episode. For patients, act now, get screened. For providers, rule the liver out.
In lieu of a final question, Roger asks panelists to describe one specific initiative they know of that is part of Global Fatty Liver Day. Mike describes a screening activity in Calgary. He describes a "mistake" last year in letting patients eat healthy food before being scanned. Louise assures him that eating healthy foods will affect scan outcomes less than 1% of the time. Jeff discusses the successes of street teams around the world, who screened 77,000 patients as part of International NASH Day 2023.
Jeff McIntyre uses the discussion between Louise Campbell and Mike Betel as a jumping-off point for discussing some of the larger care challenges and barriers associated with MASH patient care.
Jeff says the previous conversation between Louise and Michael provides "a really great synopsis" of the challenges and barriers to patient diagnosis and care. He reports that the Global Liver Institute is planning to release its first "Best Practices in LIver Health Policy" report. For GLI, these challenges are more complex due to the need to find solutions that will work in countries around the world. He also states that GLI believes the system needs to be intentional not only about diagnosis but also health system follow-through. This requires patient access and country systems set up for success. Roger raises the issue of having safe spaces for people to exercise in less developed countries. Louise recommends tier systems so that the solution for each country reflects the country's economics. Roger discusses a recent study showing a link between food insufficiency in 4-year-olds and MASLD and MASH later in childhood. Jeff describes the Stockdale paradox: policymakers cannot get caught up in the big picture without dealing with the short-term issues ahead of longer-term success.
Jeff describes two US health policy cases that reflect the Stockdale paradox: the VA's initial decision (later reversed) to require biopsy for Rezdiffra and lobbying by the giant food companies to have added sugar included in the list of attributes of healthy food.
Louise describes "a big to-do" in the UK about children's teeth and access to dentists because poor dental health drives a 7x increase in the risk of liver cancer. She would like to see a generalized dietician who can work with patients on the range of metabolic issues. Mike says it "scares" him about where to start small. Louise gives an example of boiling water before dressing wounds and taking other health actions in Angkor Wat, which led to dramatic declines in diarrhea and the spread of many diseases.
This conversation focuses on what happens after or around patient screening, addressing the challenges caused by using GLP-1s and dual incretin agonists to treat concomitant conditions before looking at the patient's liver, and then the opportunities that can come from on-site scanning and immediate feedback.
Jeff starts this conversation by noting the popularity and widespread discussion around anti-obesity medications, which also have effects on MASH. He says this could "lead to a tricky couple of years" if results include decreased willingness to participate in clinical trials and/or decreased demand for fatty liver drugs from patients already on incretin agonists like semaglutide or tirzepatide. Generally, he expresses a concern that all this will lead to a decline in focus on the liver.
Louise discusses activities in her two home countries, UK and Australia. She starts by noting that interest in the healthcare system picks up when patients go to their primary care physicians seeking care for a given disease, in this case, liver disease. She goes on to note that "liver disease is a small portion of poor liver health," which leads to cardiovascular disease and extra-hepatic cancers. Thus, she says screening should identify patients with poor liver health in order to educate and intervene with these non-hepatic conditions. She describes data in her possession that says 33% of Australians who believe they are healthy have poor liver health, and that most of these are post-menopausal women. She says there is a mismatch between patient needs, perceived resource demand, and funds available to support these resources.
Mike asks Louise to comment on scanning as an educational activity. Before answering his question directly, she discusses the value of on-site patient questionnaires in improving the quality and perceived value of the overall visit. Next, she discusses how she uses the sharing of scan results with the patient to generate a deeper patient understanding of the disease and activate conversation on how patients can help themselves better. Mike agrees based on his experience learning about his high CAP score, then lowering the level. Louise discusses steps treaters can take if the first intervention doesn't work.
This conversation centers around the Global Fatty Liver Day 2024 theme and the rationale behind focusing on screening.
It starts with Jeff describing how much has changed in MASLD in the past year and why this calls for a new focus. Jeff identifies the breadth of the global challenge of treating MASLD and related conditions, which is far broader than "just having one medicine for one aspect of the disease in one country." To Jeff and GLI, the best immediate path forward is to bring more patients into the system through screening, which provides the rationale for GLI's theme for the day, "Act Now. Get Screened."
Roger states that this effort will drop a large number of patients "in the top of the funnel," and notes that earlier podcasts demonstrate limited adoption of clinical care pathways or other ways to manage an increased patient volume. He asks Jeff where the care pathway issue fits in the "Act Now. Get Screened" vision. Jeff states this is an issue for the entire field, not just patients, and that the field needs to collaborate on a turnkey way for PCPs to screen easily.
Roger describes the concern raised Naim Alkhouri (Season 4, Episode 50.3) that the current clinical care pathway approach might create chaos in the system. Also, Roger asks whether US reimbursement policy is far enough along for the various actors to participate. Roger asks about the most effective action that patients and advocates can take. Jeff replies, "Get Screened."
Mike Betel suggests that while this may be an issue for the entire field, he believes the onus for keeping this issue in front of providers must come from patients assertively asking questions and seeking support. Jeff agrees, but describes the relationship between patient and provider in this case as "symbiotic."
On April 23, the global MASLD community lost one of its giants when SurfingMASH Co-founder Stephen Harrison passed away unexpectedly. Co-hosts Louise Campbell and Roger Green and guests Jeff McIntyre and Mike Betel each share a memory of Stephen.
Jeff McIntyre starts this conversation by remembering Stephen as a fellow Southerner and, in addition to his many professional accomplishments, a person who could cut through high-level discussions with a "pithy little West Texas saying" that would make a complex or abstract concept clear. Mike Betel starts his comments by talking about Stephen's older brother, Ken, who wrote personal messages back to every comment he could find on social media, which was a remarkable task in its own right. Mike discusses how often he heard Stephen speak and how many times he interviewed Stephen for various Fatty Liver Alliance posts or events. Mike concludes with a story about Stephen talking for five minutes while Mike's audio was malfunctioning and then doing a second take remarkably similar to the first. Louise discusses being on the podcast with Stephen for years and regrets that he will never cook her a deep-fried turkey. She recalls his hobby of building elaborate sand structures on the beach with his family while he ran around the world, putting a large dent in MASLD. Roger starts by describing the first time he saw Stephen at NASH-TAG 2019 and how his larger-than-life presence and exceptional energy suffused a room of 200 people. He continues by using a favorite "Harrisonism" about being thankful that they didn't stop after WD-39 because WD-40 was the 40th effort to create the product we know today, and comments that for Stephen as Principal Investigator, Rezdiffra was his WD-40. Finally, Roger says he "just lost it" when reading the Walt Whitman poem "O Captain, My Captain," which Scott Friedman posted on LinkedIn as a tribute to Stephen.
After the personal comments, Roger says that next week's episode will be a tribute to Stephen from some of his closest friends in the global MASLD community.
Fatty Liver Alliance Founder and President Mike Betel and Global Liver Institute Vice President for Liver Programs Jeff McIntyre join Louise Campbell and Roger Green to preview the premier MASH event for patient advocates, now known as Global Fatty Liver Day, which falls on June 13.
00:00:00 - Surf's Up: Season 5 Episode 13
Episode introduction, including brief quotes taken directly from panelists.
00:02:37 - Introduction/Remembering Stephen Harrison
Roger introduces the podcast. Each panelist shares a memory of Stephen Harrison.
00:11:44 - Groundbreaker
Each panelist shares one piece of good news from the previous week.
00:15:18 - Jeff Discusses Global Fatty Liver Day
Jeff starts by discussing how GLI came to its 2024 theme: "Act Now. Get Screened." Roger comments that this will require health systems to expand in scale and sophistication and shares Naim Alkhouri's critique (Season 4, Episode 50.3) of the current approach. He asks if US reimbursement policy is sufficiently developed and what patients can do. Jeff replies, "Get Screened."
00:25:46 - Fatty liver and obesity
Jeff notes the popularity and widespread discussion around anti-obesity medications, which also have effects on MASH. He expresses concerns that all this will lead to reduced focus on the liver.
00:26:43 - UK and AUS
Louise discusses activities in her two homes. Rather than focusing on liver disease, she prefers "poor liver health," which leads to cardiovascular disease and extra-hepatic cancers.
00:31:10 - Scanning patients as educational tool
Mike asks Louise to comment on scanning as an educational activity. Louise discusses the ability to generate an effective description and activate conversation when she delivers scan results right at the time of the patient visit. She then discusses the next steps if the first one doesn't work.
00:35:40 - Challenges and barriers for patients
To Jeff, the previous conversation between Louise and Michael provides "a really great synopsis" of the challenges and barriers to patient diagnosis and care. He announces that the GLI is planning to release its first Best Practices in Policy report. These challenges are more complex due to the need to find solutions for diagnosis and health system follow-through that will work around the world.
00:43:10 - Battles around healthy lifestyle policies
Jeff describes two challenging US health policy cases: the VA's decision (later reversed) to require biopsy for Rezdiffra and giant food companies lobbying to include added sugar as a healthy food item. Louise links the sugar question to "a big to-do" in the UK about children's teeth and access to dentists because poor dental health drives a 7x increase in the risk of liver cancer and advocates for generalized dietician training.
00:47:56 - The liver as elephant
Roger cites the parable of the blind people touching the elephant as a metaphor for a myopic view of liver health. He advocates teaching "the whole elephant" to healthcare professionals. Louise proposes an action point of "rule the liver out" before testing for related diseases. Roger suggests this is a dual mandate. For patients: Act Now. Get Screened. For providers, Rule the Liver Out.
00:51:21 - Initiatives for Global Fatty LIver Day and wrap-up
In lieu of a final question, Roger asks panelists to describe one specific initiative that is part of Global Fatty Liver Day. Mike and Jeff each describe screening activities.
00:58:13 - Question of the Week
Roger asks what listeners can do in their work to support the two simple mandates: act now, get screened, and rule the liver out.
00:58:44 - Business Report
This week's news on audience metrics, future episodes and this week's Vault conversation.
One theme in this week's episode involves different ways to use NITs in drug development and assessing the value of older drugs in MASH. This conversation, from our review of last September's FDA workshop on NITs, considers two additional roles that NITs might play in drug development.
The conversation includes Jörn Schattenberg, Louise Campbell, Roger Green, and guest Laurent Castera. The original post has an excellent description:
This conversation begins with a discussion of a point from a previous episode in 2022 about the difference between NITs to qualify patients for trials versus to evaluate the efficacy of drugs. This point stems from the idea that the way disease regresses may not be the same way it progresses. Laurent notes that NIMBLE and LITMUS have demonstrated important results with large data over the last two years. Jörn comments on the limits of using transaminase as a key NIT and Laurent replies by discussing a study over time that shows faster early declines on liver stiffness and slow declines over time as therapy might shift from reducing inflammation to regressing fibrosis. Louise shifts focus to ask about the relationship between kilopascal drops related to lifestyle change, specifically to ask whether these are false positives or real effects. Laurent notes that BMI is a confounder for liver stiffness and that CAP might help assess this issue. Finally, in response to a question from Louise, Laurent answers that we do not know about some of the key changes in test scores, and need to know more.Plenty more ideas are explored as this is both a fascinating and pivotal workshop which covers a range of topics on NITs with presentations by the some of the field's most innovative and knowledgable contributors. If you have questions or comments around the workshop, NITs, drug development or any other themes addressed in this episode, we kindly ask that you submit reviews wherever you download the discourse.
This wrap-up conversation about MASH Drug Development covers two issues: combination therapies with old drugs and using NITs to speed and smooth the path to approval.
Louise Campbell starts this final conversation by asking whether we are paying sufficient attention to old drugs that might have value in MASH. She points to a recent study demonstrating that low-dose aspirin significantly affects liver fat and suggests that we are not thinking broadly enough about use of older agents in MASH. Jörn Schattenberg comments that without robust NITs, it will be difficult to prove these effects, particularly, as Roger Green adds, for a drug that will not produce sufficient revenue for BioPharma to conduct a larger trial.
After a brief digression over whether we know how to shorten the time to drug approvals (short answer: not until we have better approaches to using NITs), Roger asks his closing question: how will having a drug approved affect the conduct of trials going forward? Answers vary and present a complex picture. You'll have to listen to learn
This conversation starts by focusing on the impact of concomitant metabolic therapies in MASH drug development and patient treatment and then moves on to explore some major implications of the earlier conversations.
Roger Green begins this conversation by returning to the issue of metabolic drugs. Specifically, he mentions a recent tirzepatide Phase 3 trial that demonstrated efficacy against symptoms of obstructive sleep apnea. Louise Campbell points out that sleep apnea correlates highly with SLD as well as obesity. She suggests this is one more point proving that we need to educate more physician specialties on liver health and educate them more effectively. Will Alazawi agrees with Louise's comment, citing a talk he and a colleague gave at the Diabetes UK conference the previous week that was part of an academic session on liver disease, noting that the session itself was well-attended. Will emphasizes applauding Diabetes UK for arranging and promoting this kind of multidisciplinary academic session of MASLD and MASH.
Roger shifts focus by asking what insights investors or other professionals who listen to the episode should take from this discussion. Jörn Schattenberg starts with the most important point: we now know how to get a drug approved. Considering other drugs in development, he adds that the drugs we are studying now may be potent enough to overcome issues that challenged earlier agents. Sven Francque adds that in future years, prior use of incretin double-agonists and triple-agonists will change the nature of the MASH patient population and make drugs like Rezdiffra that have liver-specific modes of action more important and valuable.
This conversation includes two sections: one optimizing efficacy endpoints to reflect clinical practice and a second looking back at what has improved in MASH drug development since 2020.
The first part of this discussion explores the idea that MASH drug development should reflect the clinical use of the target drug. Sven Francque starts by discussing how much larger the drug effect for Rezdiffra looks if we add lack of fibrosis progression to regression in creating the efficacy endpoint. Will Alazawi agrees but notes that the level of other metabolic diseases will also have an impact on how to assess a drug’s performance and that we do not adequately control for this in trials today. Jörn Schattenberg and Will discuss the value and meaning of stabilizing Type 2 diabetes in relevant patients.
Sven points out that the purpose of a clinical trial is different than the goal of clinical practice. Will agrees but wonders whether this might be a reason that some trials fail.
Roger Green shifts the focus of the conversation by asking Jörn Schattenberg what we have learned since the article he co-authored in 2020. Jörn points to two specific areas where the field has improved: greater consistency in reading biopsy results, and a tendency back then to rush agents into clinical trials without sufficient consideration of pre-trial data and even complex Phase 1 or 2a results. Will notes that trials that reported in 2020 were designed in the early or mid-10s, which means they could not take advantage of the innovations described in the 2020 paper. He goes on to point out that the failed trials produced data that provided the foundation for analyses from consortia and other groups. Sven commends the companies that produced this data for "digging deep" into results to find insights.
In this conversation, the panel discusses challenges in MASH Drug Development that are centered around efficacy endpoints and NAS scoring.
This conversation starts with Will Alazawi suggesting that the MASH clinical trial field suffers from the previous experience with Hepatitis C, where medications became capable of eradicating disease in a fairly linear fashion. He suggests that MASH trials undervalue the value of simply preventing progression, which leads Sven Francque to note that preventing progression to cirrhosis is now accepted by regulators as an endpoint.
Roger Green refers to last week's episode (S5 – E11), in which Michael Charlton said he would continue Rezdiffra therapy for any patient exhibiting a lack of progression, and that a clinically valuable efficacy measure must be applicable to true clinical practice. Roger goes on to recall Sven’s earlier comment that having the NAS score as a co-endpoint complicates the challenge of proving efficacy because the scale is relatively blunt and not well suited to the task at hand. He suggests that an activity score focused on inflammation and ballooning might function better than one including steatosis. Jörn Schattenberg suggests that this depends on the drug's Mode of Action.
Sven reminds the group that Stephen Harrison presented a paper at AASLD suggesting the approach Sven describes: splitting NAS into separate steatosis and activity scores, with the activity score based on lobular inflammation and ballooning. Roger asks whether the widely reported challenges in coding ballooning will render this method less valuable. Sven says it might, and states the challenge stems from the lack of detail in the scoring system.
Louise Campbell suggests that in addition to stabilizing MASH, endpoints might look at related metabolic diseases that poor liver health can affect. Will agrees, noting that many patients may be on other metabolic agents at the outset of a trial or, more challenging, the definition of "good practice" might change during the trial, which can add variability to the sample. He wonders whether differences in placebo rates can provide insight on this issue. Roger recalls a comment from Dean Tai of HistoIndex (S4 - E50.4) that some HistoIndex AI-driven analyses produce consistent placebo rates of ~33%, with efficacy rates far higher.
In this initial conversation, Sven Francque shares some of the key messages from the MASH Drug Development graveyard paper he co-authored in 2023. Jörn Schattenberg and Will Alazawi comment.
This conversation explores key points from Learnings from the Graveyard of Phase 2 and 3 Nonalcoholic Steatohepatitis Trials, which Sven Francque co-authored in 2023 with Aleksander Krag and Mazen Noureddin on lessons from recent clinical trial failures and the reasons to be more hopeful about the future. Sven starts by noting how different the world is now than when he co-authored this paper in 2023, and the reason why: we now have an approved drug. He goes on to describe three key issues the paper discussed that are still relevant: regression of fibrosis is a "high bar" for efficacy; researchers and trial sites cannot optimize heterogeneous patient samples to create samples that are more rigorously stratified, and the complexity of physiology leaves some attractive modes of action insufficiently efficacious.
Jörn Schattenberg goes back to the first issue: regressing fibrosis vs. simply stopping progression. He comments that if the challenge is to stop progression, the researcher needs to manage the trial and control groups. If the control group has disease that is too stable, the test group will likely fail to differentiate, but if the test group progresses too rapidly, it might not perform well enough. Sven agrees on the opportunity and the challenge if patients’ disease is too active.
As the conversation ends, Will Alazawi uses the metaphor of the hamburger to describe how finely balanced this kind of patient recruitment and assignment must be. The punchline: you need to hold the hamburger tight enough, but not too tight.
In this conversation, Sven Francque and William Alazawi join Jörn Schattenberg, Louise Campbell, and Roger Green to review papers co-authored by Sven in 2023 and Jörn in 2020 to discuss what failure has taught us about future MASH drug development.
00:00:00 - Surf's Up: Season 5 Episode 12
Roger comments briefly on Stephen Harrison's passing and explains why this episode will be more sedate than usual.
00:01:45 - Introduction
Opening comments from panelists.
00:02:28 - Groundbreakers
Each panelist shares one piece of good news from the previous week (NOTE: This was recorded before Stephen's death.)
00:05:10 - Sven Francque on the State of the Graveyard in 2023
Sven starts by noting how different the world is now than when he co-authored this paper in 2023. He goes on to describe three key issues in successful trials that are as relevant now as when the episode was written.
00:10:59 - Efficacy endpoint challenges
The group discusses an array of challenges: that fibrosis regressions is a high bar, that patient heterogeneity presents a dilemma for trial recruitment, and that NAS score presents its own challenges.
00:18:29 - Thinking more broadly about metabolic values
Louise suggests that in addition to stabilizing MASH, endpoints might look at related metabolic diseases that poor liver health can affect. The group considers whether placebo rates can provide guidance and reconsiders the regression and response rate issues, noting the differences between RCT patients and those in usual clinical practice.
00:28:05 - Lessons from 2020 Graveyard article
Roger asks what we have learned since 2020. Jörn points to improved consistency in reading biopsy results and greater diligence in analyzing pre-clinical data before rushing into larger late-stage trials.
00:31:49 - Implications for metabolic agents on MASH therapies
Roger returns to the issue of complex drug effects, noting a recent tirzepatide Phase 3 trial on dual agonist's effect on obstructive sleep apnea. Louise notes that apnea correlates highly with SLD. Louise and Will discuss the importance of educating more physician specialties about liver health. Will discusses a presentation he made to an academic session on MASH at the Diabetes UK conference the previous week and noted that it was well-attended.
00:36:05 - Looking ahead
Roger asks what insights investors and others might take from this discussion. To Jörn, (i) we now know how to get a drug approved, and (ii) drugs in development today may be potent enough to overcome issues that challenged earlier agents. Sven adds that in future years, the use of incretin double-agonists and triple-agonists will change the nature of therapy.
00:42:23 - Wrap-up and closing question
Louise asks whether we are thinking broadly enough about older agents in MASH, using a recent study on low-dose aspirin (S5 - E11.) . Jörn and Roger each raise a practical challenge for such a trial.
After a brief digression, Roger asks his closing question: how will having a drug approved affect the conduct of trials going forward. Answers vary and present a complex picture. you'll have to listen to learn
00:51:45 - Question of the Week
The question asks for the greatest hurdle left to overcome that will improve the percent of MASH agents achieving approval and, separately, speed approval times.
00:52:14 - Back-end report
This report includes Roger's usual weekly comment on Ukraine and Israel, followed by a tribute to Stephen Harrison.
This episode was recorded the day before Stephen Harrison's untimely passing. His influence on this entire podcast was massive. Three years after he ended his co-hosting stint, there are at least two references to his research, insights, or what we called "Stephenisms" during our first anniversary episode.
Earlier in this episode, the panel discusses different prescribing models for MASH drugs, triggered by Roger Green's question about whether MASH prescribing will resemble an oncology model. This conversation, from the EASL Congress 2023 wrap-up episodes, takes a very different view of the relationship between MASH and oncology.
The conversation includes Jörn Schattenberg, Stephen Harrison and Roger Green. The original post has an excellent description:
This conversation starts with a discussion about the importance of treating early stage cirrhosis patients. Jörn suggests that with new agents in place we may soon be looking to treat other patient populations such as, for example, those with HCC. In such instances NASH drugs will become adjuvant therapy to improve treatment against the primary disease target. Stephen agrees, noting that we will need a better test to diagnose HCC and, once available, there will be fewer presentations of advanced HCC because we will have treated more of them earlier with better agents and adjuvant therapies. Again, all this will await the approval of NASH and ideally cirrhosis drugs in the future. Roger asks how to identify the 20 to 30% of HCC patients who develop cancer before NASH. Stephen suggests it depends largely on NIT development. From there the panelists each share final thoughts around what the session has yet to cover that is important. Stephen comes up with a new idiom and Jörn speculates a new concept. Listen to the session to find out what they are.
This final conversation starts by considering prescribing models for other diseases and how they might work here, shifts to discussing the challenges of keeping a patient enrolled in a long-term clinical trial (or even participating in a trial in the first place), and moves on to the final question for the episode.
The conversation picks up on the FG-21 conversation, particularly how FGF-21 might be prescribed alongside Rezdiffra. Roger Green starts by asking whether and how this prescribing pattern might fit in an "oncology" model, where FGF-21 might be an induction drug and Rezdiffra a maintenance drug. Michael Charlton suggests that benefits from FGF-21s are likely to fade once therapy is discontinued, which would make this model suboptimal.
Jörn Schattenberg raises the issue of keeping patients in the long-term clinical trials necessary to achieve hard outcomes. Jörn advocates keeping his patients in trials but notes that long-term compliance will become increasingly challenging as more therapeutic options become available and the patient may not be improving. Michael suggests we will find similar challenges in recruitment for new trials if patients have to accept the possibility of receiving a placebo. Roger notes that biopsy requirements increase this challenge.
As the episode winds down, Roger asks participants what they believe are exciting studies likely to come to light over the next three months. Their answers vary. You'll have to listen to learn.
This conversation sees the end of the "hot topics" discussion, followed by Michael Charlton discussing issues and excitement around the FGF-21 class.
As we begin, Louise Campbell and Jörn Schattenberg speculate on ways to incorporate metrics like the Dietary Inflammation Index into multifactorial care. Michael asks whether alcohol is figured in the index, given its pro-inflammatory nature, and celebrates the fact that we can now evaluate MetALD patients as a group instead of removing them from classical MASH clinical trials. Louise, who raised the issue in the first place, does not know. As she notes, she first found the issue within the last week. One key question for her is how we can use this in 5-10 years when primary care becomes a key player in MASLD and all metabolic diseases.
Roger Green's hot topic involves "Ask the MD" columns in US newspapers and magazines. He gives "two cheers" for help columns in which MDs recommend that MASH patients "go to your doctor and ask for an ultrasound." He asks whether the PCP is the right destination and whether "ultrasound is the test to seek. However, he appreciates that all this brings MASH badly-needed visibility in the public eye. Michael and Louise agree that given how few patients are treated today, any such public acknowledgment is positive.
Michael discusses the emerging excitement around the FGF-21 class. The recent agents from Akero and 89bio are "emerging as highly potent" in terms of PDFF change and transaminase responses. While we need to learn more, he asks how this will fit in with Rezdiffra and, more generally, how long we can give a patient a "potent" growth factor and what will happen if/when the patient needs to discontinue therapy. Jörn and Michael note adherence challenges with this therapy; Roger comments that even with daily oral drugs, adherence can be a challenge.
After Michael Charlton finishes discussing research he finds compelling, Jörn Schattenberg and Louise Campbell each describe one item they have been focusing on recently.
Michael mentions the recent JAMA publication of a small, randomized controlled trial exploring the use of low-dose aspirin in biopsy-confirmed MASLD patients, which he describes as "a tremendous result." The results suggest benefits in terms of both fat fraction (PDFF) and transaminase levels. Jörn provides more detail about the trial. While the sample size was small, the results were highly promising. There is much to learn here from a larger RCT and also from understanding the biological mechanism better, but the group agrees this is a promising development.
Roger Green asks his fellow Surfers to discuss one item that has attracted their attention in the past week. Jörn Schattenberg goes first and discusses the upcoming Innovations in SLD Think Tank 2024. He expresses excitement that changes in format should yield unique, high-value benefits. Roger notes that Jörn and his co-chair Jeff Lazarus will discuss the think tank's results during the episode posting on May 15.
Louise mentions her constant pursuit of finding ways to improve prediction with FibroScan. In doing so, she found a study indicating correlation between the Dietary Inflammation index score and kilopascal level on FibroScan testing. Investigators are exploring the use of this index in an array of non-liver diseases related to metabolic syndrome or chronic kidney disease, but the correlation with kilopascals is fairly clear. Louise would like to see research looking at controlled attenuation parameter, since she can usually "see a fat change faster than a stiffness change."
Michael Charlton and the Surfers discuss two issues: defining therapeutic futility for Rezdiffra and describing some advances in MASLD translational medicine.
The conversation starts by continuing the topic of therapeutic futility. Louise Campbell asks Michael how he plans to determine therapeutic futility with Rezdiffra in terms of side effects or efficacy. Michael indicates that he will continue patients on Rezdiffra as long as their disease does not progress. While he would prefer a more robust approach, he describes the scale of challenge in defining futility for a drug where FibroScan and transaminase levels did not provide strong prediction.
Roger Green asks what percentage of patients are taking concomitant GLP-1 therapy. This leads to a brief sideline discussion on levels of therapeutic adherence.
Roger asks Michael what he find exciting in translational medicine these days. Michael cites the LiverRisk score, a developing test he describes as "substantially superior" to other biomarkers. His group is currently working with NHANES data to see whether this is predictive for patients who had transient elastography and met MASH criteria. He particularly wants to determine whether this is a dynamic test.
Michael goes on to discuss the work his group is doing on the microbiome, where he and others are finding potentially valuable insights. The challenge continues to be how to translate these insights into clinically meaningful interventions.
In this initial conversation, Michael Charlton describes some ways that the presence of Rezdiffra has affected practices and procedures in his clinic and shares issues he and his colleagues are discussing.
As the conversation begins, Michael hails Rezdiffra as proof that as a species, "we can be capable of amazing things in a good way," a drug approved by FDA to reverse fibrosis in a significant number of patients with the world's most common liver disease. From there, he goes on to discuss the challenges his metabolic live disease clinic faces in prescribing the drug. The first issue: the label provides "tremendous latitude" in defining the target F2/F3 patient properly.
Jörn Schattenberg asks about the patients coming to his clinic and how much knowledge they possess of the disease and medication. He also asks how Michael discusses Rezdiffra with them.
Michael describes a clinic with hepatology and endocrinology, nutrition support and a group of nurses all of whom can do elastography. Some patients want medication, others seek to care for themselves first through nutrition and physical activity plans. In all cases, the clinic takes a holistic approach, particularly because most patients have at least one more metabolic complication.
Michael shifts to a second issue: futility. The label does not include information on treatment-stopping criteria. He alludes briefly to a leading KOL group that is creating "something to help the field" decide which patients to treat and when to stop therapy, among other issues.
Jörn asks whether the clinic is setting up a new panel of test for these patients, Michael states that the clinic relies mostly on standard tests: FIB-4, ELF, FibroScan, and, for patients above a certain threshold, MRI.
Michael Charlton joins Jörn Schattenberg, Louise Campbell, and Roger Green for a far-reaching conversation that covers ways Rezdiffra is already impacting MASH patient treatment, exciting recent studies and broader issues in clinical trial recruitment.
00:00:00 - Surf's Up: Season 5 Episode 11
Opening comments from the panel, including brief quotes taken directly from the episode.
00:02:32 - Introduction
Opening comments (re)introducing listeners to Michael Charlton
00:04:34 - Groundbreakers
Each panelist shares one piece of good news from the previous week.
00:06:56 - Impact of Rezdiffra launch on Michael's clinic
Michael hails Rezdiffra as "an amazing thing" in terms of its global impact. He goes on to discuss the challenges his clinic faces in properly defining the target F2/F3 patient.
00:14:40 - Defining positive response and treatment futility
In response to a question from Louise, Michael indicates that he will continue patients on Rezdiffra as long as they do not progress.
00:19:44 - LiverRISK score
The conversation shifts to focus on progress in translational medicine. The first item Michael cites is LiverRIsk, which he terms "substantially superior" to other biomarkers. Next, he mentions his group's work on the microbiome and the challenges in translating items like these into clinically meaningful interventions.
00:23:15 - Low-dose aspirin as anti-MASH medicine
Michael discusses the recent JAMA publication of a small RCT suggesting benefits from use of low-dose aspirin in biopsy-confirmed MASLD patients. He and Jörn agree that while the sample size was small, the "highly promising" results might be worthy of discussion with patients.
00:26:29 - Jörn and Louise share their items of interest
Jörn discusses his excitement about the upcoming Innovations in SLD Think-Tank 2024 and its new format. Louise discusses a study indicating correlation between the Dietary Inflammation index score and kilopascal levels.
00:33:27 – Questions about the Dietary Inflammation Index
Louise and Jörn speculate on ways to incorporate this kind of result into multifactorial care. Michael asks whether alcohol figured in the index given that many MASH patients consume alcohol.
00:35:38 - Roger on patient feedback
Roger asks how panelists feel about MD columnists recommending that MASH patients "go to your doctor and ask for an ultrasound." Michael and Louise agree that given how few patients are treated today, any such public acknowledgment is positive.
00:38:11 - Excitement and questions surrounding FGF-21s
Michael discusses the emerging excitement around the FGF-21 class. "emerging as highly potent" and asks questions its use and long-term value to patients. The group discusses adherence challenges with a q1w injectable therapy.
00:41:26 Therapeutic models for MASH prescribing
Roger asks whether prescribing for FGF-21s might align with an "oncology" model, with FGF-21 as induction drug and Rezdiffra as maintenance drug. Michael suggests that benefits from FGF-21s are likely to fade once therapy is discontinued.
00:43:08 - Challenges in clinical trial recruitment and adherence
Jörn, Michael and Roger all agree on the growing challenge of keeping patients in the long-term clinical trials necessary to achieve hard outcomes.
00:47:24 - Closing question
Roger asks participants what they believe are exciting studies likely to come to light over the next three months.
00:49:33 - Question of the Week
The question asks how much value old standard drugs like aspirin or pioglitazone are likely to bring to MASH or MASLD patient treatment.
00:50:22 - Business Report
This week's news on audience metrics, SurfingMASH sponsorship, spring events and this week's Vault conversation.
This episode is a follow-up to Season 4, Episode 5, where we met Tim Jobson. His company, Predictive Health Intelligence (PHI), takes a unique approach to identifying and monitoring MASLD patients using basic EHR data and analytics. This session explores PHI's work over the past years and considers implications for several liver-related health challenges.
00:00:00 - Surf's Up: Season 5 Episode 10
Opening comments from the panel, including brief quotes taken directly from the episode.
00:02:04 - Introduction and Groundbreaker
Each panelist shares one piece of good news from the previous week.
00:07:02 - New projects from Tim
Tim discusses the three major activities that PHI has undertaken since our last visit.
00:12:46 - Sequential testing
Roger Green asks Tim to state one key lesson he would like to share with a global audience. Tim speaks of the value of sequential testing and the value of collecting data that will support this effort.
00:15:33 - Data governance and privacy
Louise Campbell asks Tim about privacy issues and GDPR status for these types of basic health information. Tim states that the number of cases where patients have exhibited concerns when they learn the data is helping them get/stay healthier is virtually nil.
00:22:31 - Most and least helpful data items
Tim states that "factual data" (e.g., lab tests) are more valuable than "coded data" reflecting a treater's point of view.
00:25:21 - Thoughts on patient gender and age
In response to Louise's questions, Tim shares that his group creates separate analyses by gender, strongly prefers creating risk thresholds to "measures of normality and abnormality," and already is seeing a trend of patients needing MASLD care at younger ages.
00:30:23 - Differences between MASLD and HCV
Tim discusses some differences in the challenge of bringing in-need HCV patients into the healthcare system compared to in-need MASH patients. HCV patients tend to live at lower socio-economic status, and some who lead high-risk lives may be homeless. MASH patients are more likely simply to lack knowledge and more likely to come to a physician visit once identified.
00:38:38 - Specific challenges in the US
In response to Roger's questions, Tim identifies two differences in the US today: greater clinician motivation due to Rezdiffra coming to market and a greater need for an inexpensive way to target the right patients and then track whether the drug appears to be working.
00:41:49 - Keeping data import simple
Tim comments that these kinds of activities are challenging enough when data sets and needs are fit to goal and fairly simple, let alone if researchers or policymakers inflate the dataset unnecessarily. This is particularly important because the system can probably locate so many untreated patients using simple data.
00:47:18 - Seeking high-value patients more effectively and final question
Louise and Tim consider what might be the "sweet spot" when patients are ill enough to appreciate that they need treatment but still hardy enough that therapy has time to work. From there, Roger asks a final question about how all stakeholders can contribute to the goal of aggregating large-scale basic sequential data.
00:52:52 - Question of the Week
The question asks what help listeners' organizations or others like them can offer in providing data or otherwise helping enrich data sources for assessing the value of repeat measures.
00:53:37 - Business Report
This week's news on audience metrics, post-Rezdiffra episode ideas and this week's Vault conversation.
This conversation comes from our coverage of The EASL Congress, 2023, when Sven Francque and Ian Rowe joined Jörn Schattenberg and Roger Green to consider primary care screening at the top of the Clinical Care Pathway. The original conversation had a robust write-up:
Ian starts this conversation by pointing to unmet needs in the primary care setting for disease identification. He refers to a related presentation of interest from Vincent Wong titled A clinical care pathway to detect advanced liver disease in patients with type 2 diabetes through automated fibrosis score calculation and electronic reminder messages: a randomized controlled trial. Ian suggests that this study proves both the value of working to identify more patients and the considerable amount of work remaining in this area. The group goes on to discuss what the implications of this study are for treatment in primary care both now and into the future of patient care. In particular, Jörn elucidates the value of FIB-4 not only as a screening tool for liver-related outcomes, but also as a predictor of cardiovascular risk and all-cause mortality. Secondly, Jörn notes that when a NASH therapy becomes available, "the granularity of picking up those patients will be higher" and physicians will be more motivated to take action provided that they have both a screening tool and available treatment to prescribe. This leads to discussion around the differences between hepatology and private medicine practices and management of a population-level disease. Ian raises the question around how frequent should testing be performed in the primary care setting for different pathways.
This conversation focuses on how the need for biomarkers will evolve in an era of in-office screening and MASH drugs and ends with answers to Roger Green's closing question.
Hannes Hagstrom starts this conversation by noting that one challenge as MASH drugs become available involves knowing when to discontinue or add to therapy since, as he points out, Rezdiffra will not be efficacious for all patients. This leads Jörn Schattenberg to the need for predictive biomarkers that will be specific to drugs or modes of action. These have not been studied much to date. Jörn is confident these will not be today’s biomarkers, but is unclear about whether they should point to genotype, mode of action or something else. After some byplay about how quickly this can come about (years vs. decades), Roger Green suggests that one key to commercial success will be the identification of this exact type of biomarker.
Louise Campbell broadens the group's focus somewhat by noting that since changes in nutrition and physical activity will be part of any regimen we need to assess the impact of these as compared to the drug itself. Jörn describes this vision as “kind of scary” but notes that diet and exercise labeling is standard for drugs in the US, exactly as it is with Rezdiffra, and these are not monitored closely. From there, we consider the kind of study one might do to assess nutrition and physical activity independently and why that might be extremely hard.
From there, the discussion moves on to Roger's final question, in which he asks what steps each panelist believes will take place in the next two years to support improved triaging and patient management through the system. Four active minds produce more than four answers. Listen to learn.
This conversation explores the implications of increased access to economically viable in-office screening, particularly when primary care practices begin to use the new scanning devices.
Roger Green begins this conversation by recalling a concern Naim Alkhouri expressed during S4 E50.3, that primary care reliance on FIB-4 can flood the pathways with many “wrong” patients, which might lead to confusion within the channels. Hannes Hagstrom describes a role for primary care at the top of the funnel if practitioners have clear guidance and training. Roger suggests this approach will make primary care providers triagists. The group agrees as long as primary care has clearer guidance based on a limited set of reliable, widely used tests and algorithms. In this context, Jörn Schattenberg suggests that while VCTE might be the first point-of-care test, perhaps EHR-based algorithms can be created and deployed to identify the optimal number and types of patients to bring into the system.
This reliance on algorithms can create another challenge. Hannes notes that many algorithms are being published but none are becoming the standards that will be key to primary care assuming a triage role. Louise Campbell feels that the fact that VCTE is fundamentally non-discriminatory between modes of action makes it a good tool as part of this, but we have lots of screening and education before bringing protocols or devices into a primary care setting. As the conversation wraps up, Hannes notes that we will need to keep some patients out of the pathway due to age or low level of disease to identify two qualifiers and that when we have multiple drugs and different lines of therapy or treatment patterns, that will recast the issue once again. algorithms are being published but none are becoming standards, and standards will be key to the primary care as triage approach. Louise Campbell feels that the fact that VCTE is fundamentally non-discriminatory between modes of action makes it a good tool as part of this, but that we have lots of screening and education to do before bringing protocols or devices into a primary care setting. As the conversation wraps up, Hannes notes that we will need to keep some patients out of the pathway due to age or low level of disease to identify two qualifiers and that when we have multiple drugs and different lines of therapy or treatment patterns, that will recast the issue once again.
This conversation centers around the different kinds of impact that in-office scanning can have on MASLD therapy, both in terms of improved prognostics and better overall outcomes.
Roger Green starts by suggesting that the recent commercialization of a second VCTE in the U.S. (specifically, Hepatoscope from e-Scopics), coupled with increased promotion of the scanning device Velacur from Sonic Incytes, will increase education and promotion dramatically and lead to significant increases in patients scanned and scan frequency. I then note the downside to this issue: increased presence of scanning devices, coupled with the fact that FDA approved Rezdiffra without requiring biopsy, might make it more difficult to recruit patients to biopsy-based clinical trials.
The group demurs whether this might motivate the FDA or EMA to move toward NITs sooner but is highly confident that it will lead to improved liver health coupled with increased access to training for prescribers and advanced providers and, separately, sensible reimbursement structures.
Jörn Schattenberg shifts to discuss LiverAIM, a new EU consortium with the goal of demonstrating that testing affects outcomes by comparing matched cohorts of 50,000 patients each. If this demonstrates the cost-effectiveness of screening, it will address reimbursement and the speed of device purchase. Louise asks whether LiverAIM will include a brief interventional therapy and conversation, two elements she finds vital in treating liver patients. Jörn states this is not the primary study objective but might occur. She asks how the study will address cultural and governmental differences between countries. Jörn expresses hope that these can fall out in analysis.
This conversation explores why different nutrition interventions might help MASLD patients improve their overall liver health and what lessons treaters and researchers can learn from this.
It starts with Louise Campbell discussing a recent publication of a pilot study from Armandi et al. (including Jörn Schattenberg as a co-author) evaluating the ability of short-term dietary gluten reduction to reduce metabolic dysfunction as measured in CAP (controlled attenuation parameter) scores. The study shows that even a short-term intervention can have a meaningful impact. The results confirm Louise’s experience with sugar-rich foods and suggest that several different diet interventions can produce valuable results. It leads to a discussion with Louise, Jörn and Hannes Hagstrom asking which change actually drives the lower CAP: gluten, associated high fructose and sugar content in the gluten-rich products, or overall calorie reduction. To Louise, the most important idea is that interventions work best with frequent VCTE tracking and multiple diet options for patients to choose. Jörn and Roger Green concur.
This conversation focuses on the role of VCTE in diagnosing, staging and treating MASLD patients, both in terms of prognostic ability of VCTE when compared to biopsy and separately as a therapeutic adjunct.
It starts with Hannes Hagstrom and Jörn Schattenberg discussing a study from Vincent Wong and a large group of co-authors, including Hannes,, that compares the abilities or VCTE and biopsy to predict outcomes. After Hannes mentions the studies and makes the key point that VCTE might be sufficient to predict the risk of outcomes in clinical trials or other events, Jörn describes the study in greater detail and goes on to ask a basic question, if a patient comes into a referral center with a VCTE-supported score of 10.2 kilopascals, what does that tell the physician about how to treat? Hannes notes a further complication: this is a tricky test to do properly, particularly in obese patients. He asks whether high kilopascal scores on VCTE should be repeated. Jörn responds that he often does the retest himself, and goes on to suggest that unlike all other tests, a repeat VCTE test four weeks later might serve a therapeutic purpose while also validating earlier results.
Louise Campbell comments that frequent retesting can have two different types of impact. During holiday season, it can inform the patient on exactly how much change increased eating and drinking has caused the liver. During more normal or therapeutic times, it can show the patient how quickly improved behavior might translate into improved liver health.
Hannes Hagstrom joins Jörn Schattenberg, Louise Campbell and Roger Green to discuss recent research panelists have conducted. This content-dense conversation focuses initially on the impact of VCTE and other forms of in-office monitoring and branches out from there.
00:00:00 - Surf's Up: Season 5 Episode 9
Opening comments from the panel, including brief quotes taken directly from the episode.
00:02:04 - Introduction and groundbreaker
Each panelist shares one piece of good news from the previous week.
00:06:02 - Introducing Topic
Roger invites panelists to share research they either participated in over the past couple of months or found particularly important.
00:06:57 - VCTE scores predict liver-related events as well as or better than biopsy
Hannes discusses a recent paper in which he participated (Vibration-Controlled Transient Elastography Scores to Predict Liver-Related Events in Steatotic Liver Disease; H. Lin et al., JAMA Online, 21MAR 2024.) This paper suggests that, in Hannes's words, "[VCTE] may be enough if you want to predict the risk of outcomes."
00:09:41 - The value of repeat measures
Panelists comment on the value and discrete benefits of taking frequent repeat measures for in-office scanning tests.
00:12:15 Changing gluten vs. reducing sugar: impact for patients
Louise mentions a recent study by Armandi et al. looking at the impact of changing gluten content on MASLD. The group discusses the benefits of offering patients multiple behavioral options.
00:20:33 Impact of increased access to in-office scanning
Roger asks whether an increased focus on overall in-office scanning may speed the replacement of biopsy with scan results in clinical trials, at least in the U.S. Panelists describe other possible benefits.
00:23:48 LiverAIM
Jörn discusses the LiverAIM consortium and its goal to improve that testing improves outcomes. The group asks whether prognostic value can provide a rationale for broader screening. Jörn suggests that LiverAIM might answer some of these questions.
00:28:56 Primary care as triage
Roger focuses the discussion on how various healthcare systems will manage the tsunami of patients likely to come to physicians' offices once a drug is available and patients are aware. Hannes describes a role for primary care that Roger describes as "triage."
00:31:05 Is VCTE a simple enough solution?
Roger asks whether VCTE can become the easy-to-interpret test that motivates primary care to engage. Jörn suggests we will need a simpler, potentially automated algorithm, possibly something like the Fibrotic NASH Index ("FIB-4 on steroids").
00:37:30 Predictive biomarkers and commercial success
Hannes notes that we will need a way to determine whether a given drug works for a particular patient. To Jörn, this raises the general question of predictive biomarkers for individual drugs or drug classes., which the group agrees will take years to sort out.
00:41:19 Diet and exercise
Louise suggests that the label statement that Rezdiffra is adjunctive to diet and exercise will require prescribers to monitor the efficacy of lifestyle intervention. Jörn and Roger note that this is standard in the U.S. language and requires little real monitoring.
00:44:20 - Closing question
Roger asks each panelist what we might achieve over the next two years to improve our ability to get the right patients to therapy.
00:49:15 - Question of the Week
The question asks what role you envision office scanning techniques like VCTE and 3D ultrasound playing in the future of patient screening and the development of clinical care pathways compared to computed tests.
00:50:04 - Business report
This week's news on audience metrics, our upcoming 4th anniversary and this week's Vault conversation.
With Louise Campbell and Jörn Schattenberg both on Easter Week vacations, Fatty Liver Alliance Founder Mike Betel joins Roger Green to continue a brief conversation they began in a post from the Fatty Liver Alliance last weekend. This conversation focuses largely on how patient incentives to participate in MASH clinical trials might need to change now that Rezdiffra is approved.
00:00:00 - Introduction
Roger explains why Louise and Jörn are not available for this conversation and welcomes Mike to a dialogue on issues they are considering in the aftermath of Liver Forum 16.
00:01:22 - The importance of convergence
Mike elaborates slightly on a comment he made in a Friday FattyLiver/SurfingMASH post on LinkedIn about the importance of thoughtful convergence between all the stakeholder groups to identify and resolve issues and why he considers the Liver Forum a great place to do this. Roger shares his understanding of the unifying challenge underlying the Forum's remit and the issue it chooses to address.
00:03:15 - Including patients in clinical trial design
Roger asks Mike what role he believes patient advocates should play in clinical trial design and bringing regulatory issues forward. Mike elaborates on the importance of including patients in clinical trial design.
00:04:47 - Three issues to consider around placebo, biopsy and clinical trials
Roger lists three issues he considers critical to consider in the aftermath of having an approved drug for advanced MASH patients: (i) requiring biopsies for trial when they are not required for treatment; (ii) willingness of patients to participate in trials when the Control group option remains placebo despite an approved drug; and (iii) maintaining trial patients on placebo to the end of Phase 4.
00:05:20 - Keeping placebo patients in clinical trials
To Mike, a key challenge for BioPharma companies will be what to offer placebo patients when they finish a clinical trial or the trial transitions to Phase 4. Roger suggests the challenge will become easier in future trials once a Standard of Care replaces placebo in the control group.
The conversation meanders through the various issues related to placebo in terms of trial assignment and continuation in Phase 4.
00:09:19 - The benefit of having the Liver Forum
To Mike, the Liver Forum brings tremendous benefit in terms of providing a forum for all stakeholders to consider these issues together. Roger points to a different benefit: the ability of companies to pool resources in situations where the cost might be too much for one company to assume. He cites the example of the Placebo Arm Database Project (discussed in Season 3 Episode 57).
00:10:52—Is the performance of a placebo group in clinical trials the same as that of untreated patients worldwide?
Mike asks whether study results for patients in the placebo control arm of a clinical trial are similar to results we would find in the practice of medicine outside the trial setting. Roger remembers an early lipids trial in which the effect of counseling overwhelmed drug impact. They discuss how complicated (if not impossible) it would be to design a trial that accurately compares the effect of a "standard treatment" group to the trial control and active groups.
00:13:28 - Can we ensure that patients in general practice get the same level of support as patients in a clinical trial?
Mike suggests that a multi-stakeholder event like the Forum should address ways to ensure that patients in everyday practice get the same support as patients in clinical trials. Roger suggests this goal may be unachievable given the limited amount of time primary care physicians can devote to a typical patient visit.
00:15:32 - Signoff
After a brief signoff, the conversation ends.
So far, this conversation has focused on Rezdiffra approval and its many forms of impact on MASLD patient advocates. This conversation considers their recommendation for others.
The conversation starts with Roger Green's final question. He asks each panelist to identify a stakeholder group that can take a valuable lesson from this episode and what that lesson should be.
Wayne Eskridge goes first. Wayne focuses on the need for Madrigal and the various professional societies to increase education and information support for the gastrointestinal community.
Mike Betel and Jenn Jones hope the Rezdiffra approval will lead to greater research investment and a broader, deeper focus for their investments. Louise Campbell returns to the need for provider education, this time for medical nursing and allied health professionals. She also believes organizations need to recruit greater nursing capacity.
Jeff McIntyre asserts that if nutrition and physical activity are critical adjuncts to drug therapy, the entire healthcare community needs to advocate for access and reimbursement to dieticians, physical therapists, exercise specialists, and other supportive professionals. Tony Villiotti returns once more to education, mentioning the need to increase scale. He also discusses some specific topics that will merit more focus.
Finally, Roger Green discusses two different forms of optimism: optimism among patients that they can be treated and, separately, optimism among investors that increasing the scale and scope of their investments will provide good returns.
This conversation asks what impact Rezdiffra patient education might have on a U.S. healthcare system in which 38% of American adults live with some form of MASLD and 15% live with MASH.
Louise Campbell starts off by saying she is “slightly fed up” with the idea that we cannot proceed too quickly for fear of overwhelming the system. Louise would rather flip focus to push systems to build the capacity they will need to handle the flow of patients that will certainly grow over time. Mike Betel agrees and discusses two Fatty Liver Alliance activities in Canada, one of which is a survey of 27,000 primary care physicians.
Roger Green pushes back slightly on Louise’s comment about overwhelming the system. He suggests that building capacity may be easier in countries with government-run healthcare systems, where one group can make and implement national decisions, than in the fragmented private US system where everything is measured in terms of short-term profit. Jeff McIntyre agrees with Louise’s point in that we can’t think in terms of “don’t burden the provider anymore.” He then discusses an innovarite solution the US Veterans Administration is implementing.
Louise points to the importance of systems solutions in view of her belief that most patient management in MASLD will fall to primary care within the next 5-7 years. This stresses the importance of systems enhancements and growing the population of advanced providers.
This conversation focuses on how the role of MASLD patient advocates might change and expand in the aftermath of Rezdiffra being approved.
To Wayne Eskridge, this “raises an entirely new field of education and outreach,” because now advocates can do more than merely be supportive emotionally. Advocates can, quoting again, “refresh our message and have broader perspectives and share a more hopeful outlook to the future” and talk about clinical trial participation and other drugs coming down the line. Also, he notes that advocates can provide the education to bring new patients into the system and help deliver the information providers will need to know in order to treat them. Jeff McIntyre adds that this will raise a new set of questions for advocates to ask companies and the healthcare system in terms of support for patients with cirrhosis, more patient-friendly dosing, reimbursement…a range of issues.
Roger Green shifts focus to ask how advocates can help slow the flow of patients into the system by reducing the rate of MASLD growth. Tony Villiotti says education is key and notes how NASH kNOWledge starts by educating children. Jenn Jones adds that education and promotion can give hope to patients with alcohol-related liver disease and those with the new category MetALD. She also notes that the label gives advocates new leverage to stress the importance of nutrition and physical activity.
This conversation focuses on the steps that patient advocates took to educate the FDA on what patients wanted in a MASH drug label, in this case for Rezdiffra.
It starts with Jeff McIntyre reflecting on apparent changes in how the FDA thinks about labeling since the initial obeticholic acid Complete Response Letter in 2020. His specific point: since that first CRL, GLI has worked closely with patient advocates, including those on this call, to educate the FDA on what their endpoints and considerations were around safety and efficacy and to help get Rezdiffra approved in the way that brings maximum benefit to patients. He points to biopsy as one proof point. More important, he believes the advocacy from patients has led to an approval process and label that “de-risks” the MASLD space for future investment.
The other panelists agree. Wayne Eskridge points back to biopsy as a particularly critical issue. Jenn Jones believes the collective effort has improved accessibility as well. Tony Villiotti acknowledges a concern that the FDA had been “dismissive” during the Obeticholic Acid Advisory Committee last year and describes himself as “pleasantly surprised” by the patient centricity of the final Rezdiffra label. Louise Campbell says this label might become a “game changer” if it signals that Madrigal will help MASH patients, most of whom live with co-morbidities, get support in navigating their array of issues.
As the conversation ends, Roger Green makes a specific point that Madrigal’s offer to support medical exceptions signifies a deep understanding of the actual challenges to early uptake and a commitment to do better than companies in the past.
This conversation focuses on advocates' reactions throughout the day on Thursday, March 14, the day Rezdiffra became the first MASH drug approved in the U.S.
Specifically, panelists discuss their thoughts and feelings as they reflected on Rezdiffra’s approval in the context of their personal experience. While no panelist is eligible to receive Rezdiffra as indicated, some thought back that day on their earlier patient experiences, while others thought of the patients for whom they advocate.
During the day, all the panelists describe themselves as having reflexively refreshed their screens, waiting for news, and a few described real concern over seeing the announcement that morning from AASLD withdrawn a little while later. Once the announcement came out officially, reactions varied.
Wayne Eskridge was the first to reflect on his reactions. He recalled his initial diagnosis in 2014 or 2015, a “very emotional” event in his office because, at that time, the diagnosis sounded like a death sentence. Tony Villiotti says the approval did not resonate with his experience, but that he felt a surge of hope for those who might benefit today and in the years ahead. Mike Betel seconds his statement, mentioning that the lack of a biopsy requirement was an excellent benefit for patients. Jenn Jones likes the idea that the drug is non-invasive and believes "this is the start of a new era" for MASLD patients of all kinds.
This conversation focuses on two issues: (i) identifying the right target MASH patients for Rezdiffra, and (ii) the extensive Madrigal patient support program for Rezdiffra.
It starts with Roger Green asking the group how the current set of target patients is defined. Jeff McIntyre points out that these are the patients currently treated for F2 or F3 MASH in the US healthcare system. Roger asks if this is analogous to the idea of “warehoused” patients observed in Hepatitis C. Jeff suggests these are quite different from warehoused patients in that warehoused patients are not being treated at all, whereas all the target MASH patients are engaged in some form of treatment.
Next ,Roger notes that Wayne Eskridge published a long post earlier in the day about the extensiveness of the Madrigal patient support program. Wayne discusses the program in some detail, in the process explaining why this process appears likely to be more engaged, interactive and helpful than the typical patient portal program.
Last Thursday, March 14, Rezdiffra (resmetirom) became the first drug approved in the US for MASH. Five leading North American MASLD patient advocates join the Surfers to discuss their feelings about this approval along with the opportunities and challenges that lie ahead.
00:00:00 - Surf's Up: Season 5 Episode 7
Opening introduction from an excited, enthusiastic panel, including brief quotes taken directly from the episode discussion.
00:05:55 - Groundbreakers
Each panelist shares one piece of good news from the previous week.
00:11:19 - Advocates recall March 14
As March 14 progressed, advocates' attitudes moved from excited anticipation to anxiety to deep happiness.
00:17:41 - Advocates describe their feelings as patients
None of these advocates are Rezdiffra candidates themselves, but each reflected on their personal experiences with MASLD and what the future holds for patients who are or will be candidates for Rezdiffra.
00:22:33 - Identifying target patients
This conversation starts with Roger Green asking the group to describe where the number "315,000 target patients" came from. After the group replies, Jeff McIntyre and Louise Campbell explain how this is different from a "warehoused" patient population, and Wayne Eskridge discusses the exciting, progressive Madrigal patient support program.
00:29:53 - The advocate's role today
Jeff begins this discussion by emphasizing the role GLI has shepherded and advocates have played in informing FDA about patients' key concerns for the label. He describes how these are reflected in the approval decision and label, with biopsy being the most obvious example. The other advocates agree, with Mike Betel emphasizing how closely the leading advocates co-ordinate with GLI and each other. Louise suggests it will be a "game changer" if FDA takes a similar view to labels for other metabolic diseases. Roger points to Madrigal's discussion of medical exception as proof of their commitment.
00:37:10 - The advocate's role tomorrow
Advocates agree that this approval creates new, broader opportunities for education and outreach. To Jeff, the approval will allow advocates to ask bigger questions on emerging needs. He offers treatment for cirrhosis and drug reimbursement as two such areas.
00:41:22 - Slowing the patient flow
Roger asks what steps advocates can take to slow the flow of patients through the progressive stages of MASLD. Tony Villiotti notes that this is the primary goal of NASH kNOWledge, starting with childhood education. Jenn Jones states that publicity about Rezdiffra may lead patients with MetALD or ALD to explore how they can protect their own livers and seek early detection.
00:46:15 - Overwhelming the system
Louise describes herself as "slightly fed up" at individuals who fear "overwhelming the system." Instead, she says, systems should build capacity to reflect the scale of the disease. Roger notes this may be harder to execute in the US than in countries where governments control their healthcare systems. Jeff points to the US Veterans Administration as a possible model for ways to build capacity.
00:52:21 - Emerging role of primary care
Louise states that much treatment will shift to primary care over the next 5-7 years. Roger agrees and seconds Jeff's comments about the role the VA can play.
00:54:55 - Closing question
Roger asks each panelist to identify a healthcare stakeholder group that needs to take a lesson from the issues discussed today. Answers vary widely.
01:02:06 - Question of the Week
The question asks what good ideas listeners have for other stakeholder groups in the aftermath of Rezdiffra's approval.
01:02:54 - Business report
This week's news on audience metrics, future episodes and why there will be no Vault conversation again this week
As the conversation wound down, Roger Green offered panelists to address any issue pertaining to Rezdiffra, the first MASH drug, that had not come up in the hour-long conversation.
The seven panelists raised eleven exceptionally diverse issues between them. Rather than provide a simple list of issues, the co-hosts invite you to listen to this short conversation to gain a fuller appreciation of each point.
This conversation revolves around one question: "What lessons should the BioPharma industry take from the launch of Rezdiffra?" Answers revolve largely around clinical trial design and, generally, taking a broad, long-term view of what the trial must accomplish to optimize drug adoption.
More specifically, Roger Green starts this conversation by noting that much of the SurfingMASH audience works in pharma or biotech. He asks what lessons they should take from this experience. Zobair Younossi responds first, commending Madrigal for “doing the right thing” and being persistent for years, even when it appeared that Rezdiffra would come to market years after the anticipated first drug. To Zobair, "the right thing" includes conducting multiple trials at different diseases and targets, including large samples in each trial, and introducing NITs as endpoints.
Jeff McIntyre also feels that using NIT markers to parallel biopsy in clinical trials has created a major bridge to an all-NIT, post-biopsy initial diagnosis plan. Louise Campbell asks what impact the two-day NIT workshop the FDA conducted last autumn had on any of this. Zobair, who works closely with the FDA, suggests that the agency is taking time to process this information collaboratively. He believes the agency is moving in the right direction, if more slowly than we might like.
One pivotal question surrounding the launch of Rezdiffra is "Which MASH patients are the correct targets for the first MASH drug?" This conversation focuses on the tools and education the health system will need to locate these patients and have them treated by the appropriate prescribers.
The conversation starts by considering educational goals. Zobair Younossi asks what is practical and proceeds to answer his own question. He starts by pointing out that most early patients will be found in GI practices. This presents a challenge. While hepatologists and their advanced providers have the knowledge they need to identify patients and prescribe, most of the target patients are being treated in gastroenterology practices, and this group is not as knowledgeable about the disease, screening, staging and treatment. For 2024, he says, educating this group must be the primary focus of education. Zobair notes that other specialty organizations are aligned with the need to screen, stage and treat, but the lay practitioners in these specialties also will need education.
Jeff McIntyre agrees strongly with Zobair’s assessment. Jeff asks: education to what points or outcome? Jeff views education as needing to address two issues: proper prescribing and use of the drug, but also proper identification of patients. To Jeff, these are the key needs in educating gastroenterologists and their advanced providers, but also key issues for educating patients so they can advocate effectively for themselves.
Jörn Schattenberg states that Rezdifra’s safety profile is a critical benefit. It alleviates some concern that a well-meaning provider might prescribe for a patient with compensated cirrhosis due to a lack of precision with current tests.
Roger Green notes that the excellent Rezdiffra safety profile will resolve a dilemma physicians have with most first-in-class drugs: how to do no harm while getting the drug to the right patient. This safety profile makes the dilemma less profound, although it is no less important to keep in mind.
Returning to education, Laurent Castera closes this conversation by noting that he works at a “liver clinic inside a diabetes clinic,” and that the diabetes screening protocol—an annual FibroScan for every patient with suspected advanced liver disease, followed by referral to a hepatologist—is working well.
This conversation focuses on the necessity of using NITs to screen and identify Rezdiffra patients, while at the same time acknowledging the shortcomings of current tests. Panelists suggest some different NIT testing strategies while commenting on upsides and potential challenges for each MASH NIT.
Laurent Castera joins the conversation at the beginning, which is helpful given his extensive research and knowledge of the surrounding communities. Laurent points out that distinguishing F3 patients from F4 will be a difficult challenge to solve, in part because we used categorical scores for fibrosis instead of recognizing that it is, in fact, a continuum where, in Laurent's words, "you are not 1.2 or 1.5. You're F1, 2, 3 or 4." Having a drug will facilitate a shift from the old-school categorical view to a more linear one.
Laurent goes on to comment that it is not clear exactly how we will use NITs, but that liver stiffness will certainly be one key metric, one he describes as "a prediction scale." He also comments on the problems caused by relatively low arbitrary cutoffs here, 12.25) and the need for (a) repeat measures and (b) use of at least two tests. He mentions platelet counts as one important example.
Jörn Schattenberg discusses the importance of clinical observation and judgment. Zobair Younossi takes that point further to stress the importance of conservative judgment in assessing for cirrhosis. Laurent suggests that a second, "more specialized test" that is "not related" to VCTE will tremendously improve accuracy.
I comment that one important issue is that individual prescribers will now start treating with Rezdiffra and will derive opinions about the drug based on their experiences with the first few patients for whom they prescribe. I suggest that similar patterns may be true for NITs and ask how panelists anticipate providers will receive education on NITs.
Louise Campbell talks about the roadmap that Madrigal showed of what they're going to have their reps and MSL trained doctors on and believes that will be exceptionally helpful. She also feels it is vital that practitioners early in the patient visit change also be well-educated on this topic. She notes that many of the people focusing on this topic, including former panelist Suneil Hosmane, now at Madrigal, are first-rate.
Jeff McIntyre closes the conversation by suggesting there will be a "huge patient role," because patients are people who can demand, or at least ask questions of doctors that will lead the doctor to do things they might not otherwise and to get more informed on related issues. Jeff notes that we have not come up with an adequately specific answer to the question, "What's the best NIT?" which mandates that we keep educating and speaking out.
This conversation focuses on what panelists see as a key (and somewhat unusual) benefit of Rezdiffra: that having a prescription drug for MASH creates a better environment for discussing lifestyle intervention and improving overall patient adherence with diet and exercise.
This conversation focuses on the impact of having a drug on getting patients to comply with lifestyle interventions. Zobair Younossi starts by noting that, historically, it has been "very difficult" to institute successful lifestyle interventions because patients "are not used to thinking about lifestyle as a prescription." Now, providers can counsel patients to adhere to a regimen that includes medication and lifestyle changes.
Jörn Schattenberg notes that Rezdiffra is indicated in the label as an adjunct to diet and exercise, which is common wording for most metabolic drugs. Zobair agrees but notes that this is still difficult to achieve in practice. One example: in the US, not everyone can comply with the idealized Mediterranean diet. As he notes, diet recommendations must be geographically and culturally relevant.
I note that in my 25 years of marketing research, one thing I learned was that physicians feel they "have nothing" when all they can offer patients is lifestyle modification. With a drug in the discussion, the provider can "flip the script" to make lifestyle intervention adjunctive to the drug. Jeff McIntyre points out specifically that having Rezdiffra to prescribe will help reduce stigma by "medicalizing" the recommendation to lose weight and add exercise. In effect, Jeff says, this takes the onus off the patient to feel responsible for their own disease. Zobair discusses a recent publication from the Global MASH Council on the impact of stigma.
At this point, Laurent Castera joins the conversation. He adds the thought that having a drug to prescribe will increase interest among primary care providers. He also notes the importance of the label coming without a biopsy requirement, "a very important message to convey." The conversation ends with Ian Rowe sharing his concern that it will be "quite difficult" to differentiate patients living with advanced fibrosis patients from those living with cirrhosis.
FDA approval of the first MASH drug, Rezdiffra, on March 14 marked what co-host and Key Opinion Leader Jörn Schattenberg describes as a "watershed moment" for hepatology. This opening discussion covers how panelists heard the news of Rezdiffra's approval, how they reacted, and their initial thoughts about appropriate patient targets.
As the conversation starts, the various panelists describe their moves throughout the day on March 14th and their reactions when word of the FDA's approval came. They all describe having felt various degrees of trepidation as the day progressed. Jeff McIntyre describes him and his friends as "constantly refreshing our screens" throughout the day. Zobair Younossi probably felt less anxiety than others, while some of the Europeans described feeling more.
This was replaced by excitement and joy at the final announcement. Jörn Schattenberg describes the day as a "watershed moment," that, in Zobair's words, "energiz[ed] for the entire field."
Panelists go on to describe the patients they expect to prescribe Rezdiffra for at launch (now for the US, whatever comes available on the EMR). Jörn intends to prescribe initially for F3 patients but realizes he might not know exactly how to distinguish them from early-stage cirrhosis. Zobair points to prescribing for F2 and F3 patients as indicated in the label.
Last Thursday, March 14, Rezdiffra (resmetirom) became the first MASH drug approved in the US. A global panel of Key Opinion Leaders convenes to discuss their excitement about this approval, the opportunities it will create and some of the (largely manageable) challenges it might present.
00:00:00 - Surf's Up: Season 5 Episode 6
Opening introduction from an excited, enthusiastic panel, including brief quotes taken directly from the episode discussion.
00:05:02 - Groundbreakers
Each panelist shares one piece of good news from the previous week.
00:08:15 - Waiting for news and initial reactions
Panelists describe their moods throughout the day on March 14 and reactions when word of the approval came from FDA. They describe feeling varying degrees of trepidation as the day progressed without word from the agency, replaced by excitement and joy at the final announcement.
00:14:30 - Specific patients to target or avoid
Panelists describe the patients they expect to prescribe Rezdiffra for first (now for the US, when it becomes available for EMA). The group aligns on the benefits for F3 and F2 patients (the two groups listed on the label) but shares concerns about accurate identification of F3 vs. compensated cirrhosis.
00:17:07 - Impact on explaining lifestyle interventions
Zobair Younossi notes the historical difficulty of getting patients to view lifestyle modification as a specific prescription to be followed. He, Roger and Jeff all makes points to suggest that the combination of drug + lifestyle modification will be easier to explain to patients.
00:26:32 - Staging and screening patients using NITs
Laurent Castera joins the conversation as the topic switches to proper use of NITs. Previously, Jörn Schattenberg and Ian Rowe touched on challenges in deciding which patients have F3 fibrosis vs. early stage cirrhosis. Now the group explores the relative value of different strategies for qualifying patients. One key: while FIB-4 is an efficient screening test in largely negative populations, it produced a high level of false positives in specialty practices.
00:33:50 - How to educate providers
Roger points out that individual providers will conduct individual "clinical trials" in their own practices. This makes provider education on proper use critical to launch success. Louise Campbell commends Madrigal for the education pathway they laid out during the webcast. Jeff discusses the important role patients must play.
00:39:06 - Finding the initial patients
Apropos of education, Zobair points out that most early patients will be found in GI practices. Jeff points out that these patients are already in the system and can be easily identified.
00:43:12 - Why Rezdiffra's strong safety profile matters so much
Panelists agree that Rezdiffra's safety profile alleviates some concern that a well-meaning provider might prescribe for a patient with compensated cirrhosis due to inadequacy of current tests.
00:48:39 - Suggested takeaways for industry
Panelists suggest that industry learn from the large sample sizes and thoughtful use of NITs found in the Rezdiffra trial protocols.
00:52:20 - FDA and NITs
Louise asks how important FDA's two-day NIT workshop last year was in the agency not requiring biopsy prior to prescribing. Zobair says agency officials are moving slowly down a path toward greater acceptance.
00:53:53 - Closing Thoughts
Each panelist shares a closing thought. The topics vary widely.
01:01:06 - Question of the Week
The question is what impact Rezdiffra's approval will have on individuals' day-to-day work.
01:01:47 - Business report
News on audience metrics, future episodes and why there will be no Vault conversation this week
This conversation comes from our first look at MASEF, last September, when lead author Mazen Noureddin joined the Surfers to discuss his recent breakthrough paper on this new NIT. The original conversation had a robust write-up:
Mazen Noureddin joins co-hosts Jörn Schattenberg, Louise Campbell and Roger Green to discuss serum identification of at-risk MASH and the Metabolomics-Advanced Steatohepatitis Fibrosis Score (MASEF). In late July, Mazen co-authored a paper on the subject which was published in Hepatology.
This conversation begins with Louise’s initial response around the setting of application for MASEF. She poses a question that leads the group to explore possible pros and cons of different approaches and the potential impact each might have in terms of cost effectiveness. For example, Jörn wonders how feasible it will be for non-experts to administer. Mazen suggests that its application will be relatively easy before explaining how to navigate the caveat of a gray zone similar to that of VCTE. After a few more comments on sequential pairing with FIB-4, Mazen next teases the possibility of demonstrating therapeutic efficacy in the drug development space.
Louise returns to a question around cohorts and asks whether variables like age or sex has an impact on the test’s capabilities. She then asks whether this sort of work has the potential to inform retrospective cardiac studies. After Mazen and Louise go back and forth with a few ideas in response, Roger makes the comment that he is struck by the wide breadth of application and describes the platform as “elegant.” As the conversation winds down, the group discusses a few comparisons between different blood-based markers.
If you have questions or comments around MASEF, metabolomics or any other ideas considered in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com. The Surfing the NASH Tsunami will be back next week with more original content.
After some final discussion about GLP-1s, this conversation entails Roger Green summarizing what he has heard in the episode so far and testing for confirmation or correction. It goes fast and covers significant ground.
Naim Alkhouri starts this conversation by discussing patients for whom he would prescribe resmetirom vs. GLP-1s. Lean MASH patients are likely to receive resmetirom. Earlier fibrosis patients are more likely to receive semaglutide. A multimorbid F3 patient might receive both.
Roger asks how things might change with tirzepatide, since it is a dual agonist with strong MASH-lowering effects. Naim expresses doubt that tirzepatide will be antifibrotic, since neither GLP-1 nor GIP have direct liver effects. He has more faith in the glucagon dual- and triple-incretin agonists.
The rest of the conversation involves Roger stating themes he has heard earlier and asking for confirmation or amendment. It moves pretty fast, covers a lot of territory, and receives some agreement and some correction.
This conversation touches on two important subjects: the impact of different potential resmetirom prices on the size and structure of the treatable MASH population, and the impact GLP-1s are having (and will have) on clinical trial recruitment and basic patient treatment.
It starts with Naim Alkhouri expressing concern over the $39-52K price he has heard for resmetirom, which ICER has deemed cost-effective. He mentions another paper that says a price of $19,000 would be cost-effective. To Naim, this magnifies a question that is already quite widely considered: when to prescribe resmetirom vs. a GLP-1 agent. He discusses some patient factors that might go into his decision.
Naim describes ways that GLP-1 use, which can be sporadic or episodic, is affecting clinical trial recruitment. Ian Rowe discusses the current use of GLP-1s in the UK and suggests that if the price for resmetirom is high enough, GLP-1s will receive significant use.
Naim Alkhouri shifts direction slightly, from discussing current GLP-1s to exciting recent clinical trial report. He focuses on two: survodutide from Boehringer Ingelheim and efruxifermin from Akero Therapeutics. Recent exciting results from BI and Akero suggest to Naim and others that the future for drugs is bright.
Ian Rowe anticipates a significant amount of co-prescription of GLP-1s and resmetirom in this population. GLP-1s have already demonstrated clear cardiovascular, weight loss, and HbA1c-lowering benefits. To Ian, that creates sufficient motivation to prescribe GLP-1s to multimorbid patients with diabetes, obesity and most likely MASLD or MASH. To him, the price of resmetirom will have a tremendous impact on how often UK physicians rely on GLP-1s alone.
This conversation focuses more tightly on the specific challenges with the current approaches that use NITs to diagnose and stage advanced MASH fibrosis and explores several newer options and ways of thinking about the challenge.
Roger Green notes that recent papers discuss the failure to predict accurately with FIB-4. He asks how we can improve predictive performance. Louise Campbell notes some specific challenges, after which Jörn Schattenberg praises John Dillon's work in automating lab detection algorithms. He also reiterates his view that repeat testing will be pivotal in good test protocols. Ian Rowe rejoins the conversation (from a faulty Internet connection) to comment that our inability to stage patients reliably will lead to government payers like NHS believing that they will need biopsy to stage patients accurately and treat them cost-effectively. Jörn says Germany will work differently and if EMA approves it, it will launch in Germany.
Roger asks about new tests on the horizon and specifically whether there is sufficient improvement in diagnosis, staging or treatment. He refers specifically to MASEF and Naim Alkhouri's earlier comments about four scan vendors at his conference. Ian says there are tests that can rise to this task, but they are not produced in sufficient quantity and cost too much to become a first-line option. Naim notes that the most exciting tests are a couple of years away. Ian returns to Jörn's earlier point about the value of sequential testing vs an individual test. Louise suggests that device size will be pivotal for primary care.
This conversation explores the challenges with using the current non-invasive tests (NITs) to diagnose patients with F2/F3 advanced MASH fibrosis. If tests today cannot achieve the requisite level of precision, panelists explore other ways to define patient targets.
Roger Green starts by recalling that in a recent episode (Season 5 Episode 2), Jeff McIntyre suggested that in the US, the initial patient population may be as small as a few hundred thousand people. Ian Rowe states that current tools are incapable of placing these patients in a narrow diagnostic or therapeutic window. Jörn Schattenberg takes a "pragmatic" approach to defining the patient he is certain to treat; test results are a small part of his calculus.
Naim Alkhouri shifts the discussion to focus on VCTE cutoff points for cirrhosis. The interplay between Naim and Ian suggests that different practices and guidelines carry with them different cutoffs. Jörn expresses gratitude that the can watch the US and learn from that experience. He notes the tension between wanting a cost-effective system and large numbers of patients clamoring for the new medicine. The need to rule some patients out is obvious, the way to do so is challenging.
Asking, "What can we do besides scan" or use conventional tests, Naim discusses some newer options, starting with the metabolomics-based MASEF score discussed in Season 4 Episode 39. He also mentions the LiverFast test. Jörn describes factors that can render a test inappropriate for a particular patient. Louise suggests the right test will depend on the specific question the provider is trying to answer.
This conversation explores why proper use of non-invasive tests (NITs) will play a pivotal role in increasing the number of patients diagnosed and treated for MASH. It becomes particularly pivotal if, as expected, the first MASH drug is approved later this month.
Roger Green starts this conversation by describing why he considers NIT use and adoption one of the two pivotal patient treatment issues for 2024. Jörn Schattenberg notes that he has not received any referrals from PCPs or endocrinology based on elevated FIB-4, which would happen if enough front-line treaters were adopting the new clinical care pathways. Educational efforts have begun, but do not seem to be changing behavior yet. As Jörn puts it, "We're still preaching, and I haven't seen it in much activity."
Naim Alkhouri states that his experience is the same as Jörn's. He reminds us that we covered some of these issues in a 2023 end-of-year conversation (S4 E50.3). He reiterates his concern with FIB-4 as a standalone first-line test and states his preference for combining it with an in-office scan. He comments that at the recent Desert Liver Conference, four companies displayed these devices, each with a different price point and convenience factor.
Ian Rowe describes the British experience as being different: "every patient with elevated ALT in the context of metabolic risk factors has a FIB-4 and now has a FibroScan." His biggest concern is that tests are insufficiently precise. If we have top-end and bottom-end cutoffs, he fears, "you're going to end up excluding a lot of patients who would be potentially eligible for treatment."
In 2024, the two major areas for change in diagnosing and treating MASH are new drug approval and changes in use of NITs. Naim Alkhouri and Ian Rowe join Jörn Schattenberg, Louise Campbell and Roger Green to consider what might change with NITs and how having an approved drug might change thinking on this issue.
00:00:00 - Surf's Up: Season 5 Episode 5
Opening introduction, including brief quotes taken directly from the episode discussion.
00:02:36 - Introduction and Groundbreaker
Panelists congratulate Naim on the recent, highly successful Desert Liver Conference. In the groundbreaker, each panelist shares one piece of good news from the previous week.
00:06:36 - Why Focus on NITs?
Roger describes why he considers this issue worthy of an episode. Naim and Jörn both state that they have received no referrals from PCPs or endocrinology based on elevated FIB-4 tests. Ian notes that the UK has guidelines and pathways built into some protocols; these make it challenging to stage a patient as F2 vs F3 vs early compensated cirrhosis.
00:13:06 - NITs and treating F2/3 MASH patients
Ian says that current tools are incapable of defining the small initial target patient population Jeff McIntyre suggested in Season 5 Episode 2. patients clearly enough to place them in a narrow diagnostic or therapeutic window. Jörn takes a "pragmatic" approach to defining the patient he is certain to treat; test results are a small part of his calculus. Naim shifts the target patient to focus on VCTE cutoff points for cirrhosis. There is no clear cutoff.
00:18:45 - Tests worth using beyond the widely discussed options
Asking, "What can we do besides scan?" or use conventional tests, Naim discusses some of the new blood-based tests. Jörn describes factors that can render a test inappropriate for a particular patient. Louise suggests the right test will depend on the specific question the provider is trying to answer.
00:22:59 - Improving on FIB-4
Roger notes that recent papers discuss failure to predict accurately with FIB-4. In the conversation that follows, panelists agree that automating test results and using a series of tests instead of a single event will both have real value.
00:28:27 - New Devices and Blood-Based Tests for Use in Office
Roger asks about new tests on the horizon and specifically whether there is sufficient improvement in diagnosis or treatment. Naim notes that the most exciting tests are a couple of years away. Ian returns to Jörn's earlier point about the value of sequential testing vs an individual test. Louise suggests that device size will be pivotal for primary care.
00:35:30 - Impact of Resmetirom Price
Naim expresses concern over the $39-52K price he has heard for resmetirom. Roger states that price reflects size of target market. At that point, the discussion veers toward factors that drive drug prices higher.
00:40:22 - Impact of GLP-1s on treatment and resmetirom
Roger asks the group what the impact of consumer-driven GLP-1 use is likely to be on US prescribing of MASH drugs. Ian discusses use of GLP-1s in the UK and suggests that if the price for resmetirom is high enough, GLP-1s will receive significant use. Recent exciting results from BI and Akero suggest to Naim and others that the future for drugs is bright.
00:47:16 - Final question
This entails Roger summarizing what he has heard in the conversation and testing for confirmation or correction. It goes fast and covers significant ground.
00:53:26 - Question(s). of the Week
The question is what else will change, besides prescribing, once a drug is improved and what the industry can to do optimize change.
00:54:06 - Business Report
News on audience metrics, the upcoming Question of the Week, future episodes and this week's Vault
Two years ago, Surfing the MASH Tsunami conducted two episodes with Chris Estes, then the chief modeler for the Center for Disease Analysis Foundation exploring issues around CDAF's then-recent publication of a NASH/MASH disease model. This conversation centers on issues of advanced fibrosis. We thought it might be interesting to look back at that episode in lieu of today's topic. Here are the summary notes from 2022:
*This conversation starts with Chris Estes describing the processes he and his colleagues at the Center for Disease Analysis Foundation have used to build a disease model for NAFLD and NASH prevalence in 15 countries. Chris discusses some of the unique challenges that modeling NASH presents. Among other items, these include (a) spontaneous regression of disease; (b) "excess" mortality (mortality not from liver disease where NASH is a contributing factor); and (c) interplay of demographics (gender, age, race, etc.) and co-morbidities (most notably Type 2 diabetes) with disease.
When Chris ends his initial comments, Jörn Schattenberg asks about the viability of using obesity as the anchor for increasing prevalence estimates instead of diabetes, noting the varying definitions of BMI across countries. Chris notes that obesity is imperfect but adds that we have robust, stable, long-term obesity data bases in most countries, whereas diabetes estimates are newer and many people with diabetes to not recognize they have the disease.*
The last element in this conversation starts with Alina Allen noting that for clinical trial development, researchers test patients with a range of diagnostics. As a result, they do not need to develop estimates based on (or even linked directly to) obesity or diabetes. Alina asks what models can tell us that can help bring down high placebo rates in double-blinded, placebo-controlled clinical trials. Chris mentions meta analyses as recently as seven years ago that exhibited negative disease progression over time and adds that any assessment of F3 (or even F2) fibrosis is affected by concomitant disease.
This conversation is sponsored by Resoundant, a Mayo Clinic company and the developers of Magnetic Resonance Elastography. MRE is widely available with over 2000 locations worldwide, and can be done as a low-cost, rapid exam in just 5 minutes. Together with PDFF, this quantitative exam is called an Hepatogram – a powerful non-invasive alternative to liver biopsy in many cases. For more information, visit www.resoundant.com on the web.
As the episode comes to an end, the group winds up focusing on the need for better, more frequent MASH education as a pivotal need if we are to flatten the growth curve of the MASLD pandemic. In the process, the discussion returns to the risk for women and the important role they can play.
Louise Campbell starts this conversation by harkening back to the issue of post-menopausal women. As she notes, women provide most of the hands-on care in health system, and also do most of the cooking and food shopping for the home. To Louise, targeting women also targets children, so educating women will have multiple derivative benefits.
Zobair Youonossi agrees completely, particularly for the low SDI countries. I suggest that slowing prevalence and disease has two elements: fewer patients at the starting line (or with early MASLD) and better therapies and programs for patients who already live with the disease. I also ask whether the consumer uptake of GLP-1s might have an impact in the US.
Zobair states that educating children is the key long-term driver and that the effect of consumer medical behaviors like taking GLP-1s is likely to be minimal. He also believes that MASLD requires more attention from global and national governmental and non-governmental players…NOW!
This episode does not have a formal closing question, but the rest of this conversation offers a wrap-up of each panelist’s perspective.
This conversation focuses largely on the work of the Global NASH Council, an effort of over 200 stakeholders in more than 50 countries to address a range of macro issues in the MASLD space.
Zobair Younossi, who is the Global NASH Council Chair, starts this conversation by discussing a specific Global NASH Council project on how to implement guidelines for different specialties across regions. He offers two reasons this is such an important project.
- In general, Zobair notes, 90% of the content in guidelines is virtually identical, but the other 10% might vary widely. The goal of the Global NASH Council is to identify this last 10%, understand the reasons for these differences, and seek to align them better.
- As he points out, guidelines are worthless without effective implementation. The second goal of this project is exactly that: to improve implementation.
Zobair goes on to discuss other Global NASH Council projects, ranging from shared biopsies to the previously mentioned modeling activities. He notes its growth in size and expresses gratitude to the other global MASLD leaders, including Jörn Schattenberg, who are part of one of more of the Council's major projects.
Roger Green asks Zobair to put the guidelines project and the Council's policy focus in the context of his earlier comments about high SDI vs. low SDI countries. He describes differences in what food insecurity means between the two types of nations and how that should affect each country’s pursuit of policy and guidelines. He also suggests that it will be more important to provide patient and provider information for specific low SDI countries.
This conversation starts with a focus on slowing the growth of the MASLD pandemic, and then veers slightly into a discussion of the specific issues post-menopausal women face with MASLD.
Roger Green starts by commenting how it seems both pivotally important and highly efficient to find a way to flatten the growth curve, and he asks Zobair what he considers key to doing so. Zobair replies that the key is to focus on multidisciplinary care centered around primary care, which will require extensive physician education. He also comments that countries may differ widely in what their current MASLD priorities should be. He introduces the idea of the sociodemographic index and the difference between high and low SDI countries. To Zobair, it is critical to elevate the issue of how to support low SDI vs. high SDI countries, which involves, in different ways, every stakeholder from WHO down to patients and their advocates.
Louise Campbell shifts focus to point out that the article raises a point about the increased risk of MASLD to postmenopausal women. This brings up a range of comments, the most important of which revolve around the need to educate OB/GYN physicians and their allied providers on the important liver risk to post-menopausal women.
Initially, this conversation focuses on how cost-effectiveness issues relate to the MASLD Disease Burden. In the process, Zobair Younossi provides education on some of the metrics and concepts pivotal to drug value assessment.
Roger Green starts off asking how the economics of treating MASH stack up against hypercholesterolemia at the birth of statins in the 1980s, where the medical benefit was clear but economic was harder to manage. Zobair proceeds to describe the process by which the cost effectiveness of drugs is measured, computation of Quality Adjusted Life Years, or QALYs, and how different countries vary in the level of QALYs they consider cost effective. He also notes that within the US, at least, we may be willing to accept five times greater cost per QALY than for another. He also points out that cost effectiveness grows as new therapeutic options include price competition into a market.
Louise Campbell shares the specific US cost numbers from Zobair’s article, which she describes as “frightening,” particularly given the rate of growth in the disease and society’s lack of efficacy in shifting the curve on this. Zobair responds by saying that one goal of the article was to create awareness that regular surveillance of diabetic patients for MASLD could have a significant economic impact in the US.
As the conversation winds down, Jörn Schattenberg comments that all this is a team effort and Zobair agrees heartily.
In this opening conversation on MASLD disease burden, Zobair Younossi summarizes and expands on some key points from the recent Diabetes Spectrum review article he co-authored with Linda Henry.
Zobair starts by discussing the recent review article, Understanding the Burden of Non-Alcoholic Fatty Liver Disease: Time for Action which he describes as "a summary of a large body of evidence that's being generated." He points to three pivotal issues:
- The treatment burden associated with MASLD and MASH is extremely high and will grow over time. The prevalence of MASLD in the overall population has grown to ~38%, but for Type 2 diabetics, who have worse outcomes associated with MASLD, this number is 68%. MASH numbers are estimated to be 5-7% in the general population, but 37% among T2D patients. As diabetes increases across the globe, these rates will go higher.
- The humanistic burden, as measured in Quality of Life scores, is also significant. Patients living with MASLD and MASH report lower QoL scores, which translates not only into a less happy, more depressed society, but also into significant indirect economic effects due to poorer worker performance and, presumably, more time away from work.
- The economic burden of MASLD is significant in every country, but the scale and structure of this burden varies from country to country. Key drivers include dietary issues and inactivity, and issues are becoming more pronounced globally. These economic issues are driven largely by the key downstream sequelae. The leading causes of death from MASLD are cardiovascular disease and extrahepatic cancers, which are costly, and patients with cirrhosis are highly susceptible to liver cancer as well.
Jörn Schattenberg joins the conversation to commend Zobair on his work, which, as Jörn puts it, "educate[s] us as physicians on where the risk factors and the at-risk populations are, and we're moving that way. I mean, we're trying to focus on patients with diabetes that are more advanced from the hepatologist perspective." He also discusses the ongoing effort to educate endocrinologists and primary care about these issues as well, since those two specialties treat the lion's share of diabetic patients.
Zobair goes on to describe the Markov models of disease cost his group has built already in seven countries, and plans to build in more. Key point: MASLD is costly everywhere, but the structure of cost and, most importantly, public health solutions will vary from country to country.
Zobair Younossi, Chair of the Global NASL Council, publishes seminal papers on MASLD epidemology, cost of disease, and related public health needs regularly. Co-hosts Jörn Schattenberg, Louise Campbell, and Roger Green ask questions and share perspectives from their own experiences.
00:00:00 - Surf's Up: Season 5 Episode 4
Opening introduction, including brief quotes taken directly from the episode discussion.
00:02:45 - Introduction and Groundbreaker
Panelists swap brief, lighthearted comments about where they are geographically and where they have been recently. In the groundbreaker, each shares one piece of good news from the previous week.
00:11:15 - Epidemiology article
Zobair Younossi discusses the recent review article, Understanding the Burden of Nonalcoholic Fatty Liver Disease, published earlier this month in Diabetes Spectrum. He starts by discussing incidence and growth rates for MASLD, MASH, and cirrhosis across the world, and how these differ by country. He goes on to discuss the impact of MASH on patient Quality of Life and the high correlation between multi-metabolic patients (most notably diabetics) and negative outcomes.
00:15:55 - Panel questions and comments
Jörn Schattenberg joins the conversation to praise this and other of Zobair's works for helping physicians know what to do when they decide to become more engaged in treating MASLD and MASH. This leads Zobair to discuss the Markov model they have created to evaluate burden of disease.
00:19:14 - Costliness and cost-effectiveness of therapy
In response to a question from Roger Green, Zobair describes the criteria and metrics used to evaluate the cost-effectiveness of a new drug or diagnostic. Louise Campbell comments on how high and underappreciated the social and economic burdens of disease are to every global society. Zobair notes that health economists do not focus on liver disease as a discreet set of costs and burdens.
00:27:17 - Goals and activities for the next few years
Roger states that given how fast the MASLD and MASH populations are growing, an effort to "flatten the curve" would be heroic. Zobair replies that each country needs to fight liver disease, but that each country will have different immediate challenges.
00:31:28 - Women's health and liver health
Louise notes that the epidemiology paper refers to the high level of risks among women over 55. This leads to a discussion between Jörn, Zobair and Louise on the higher risk level post-menopausal women experience and some pathological elements that make this important.
00:34:58 - Global NASH Council
Zobair bridges this portion of the conversation to discuss the work of the Global NASH Council, a group of >200 members in >50 countries organized into different workstreams to create knowledge and awareness around MASLD and MASH.
00:38:59 - Low SDI and High SDI countries
To Zobair, one element in the global effort on MASLD and MASH is the recognition that High SDI (wealthier) and Low SDI (power) countries face dramatic differences in the challenges they face.
00:41:14 - Reducing the rate of disease growth
To Louise, educating women might be a key to driving awareness, both because post-menopausal women live at higher risks and because they cook and schedule for their families. This leads to a broader discussion about the most effective education starting with children. Finally, Zobair discusses the importance of making all stakeholders PLUS global agencies recognize the scale of this challenge and to act in concert with increasing urgency.
00:48:42 - Question of the Week
The first Question of the Week asks what steps each of us can take to help stem the pandemic.
00:49:41 - Business report
News on audience metrics, the first Question of the Week, next week's episode and this week's Vault conversation
Our first conversation focusing on the new MASLD nomenclature surfaces as part of our coverage of the EASL Congress 2023. Hepatology researchers and key opinion leaders Sven Francque and Ian Rowe joined Jörn Schattenberg and Roger Green to discuss the value of the new nomenclature and its current and anticipated impact on their practices.
This conversation focuses on the outcome of the nomenclature process, a three-stage Delphi process that produced new names and classifications for what had previously been known as fatty liver disease and henceforth will be known as steatotic liver disease (SLD). Sven, who was actively involved in the entire exercise, gives a concise summary of the process by which the new classifications were developed and how the new terminology will work. The rest of the conversation focuses on three issues.
- Excitement that we will now have the opportunity to study patients whose disease has both metabolic and alcohol-based components.
- The processes by which the three clinicians, Sven, Ian and Jörn are starting to share the new structure with their patients with varying degrees of success. One interesting observation emerges here from Sven: the English language terms do not translate equally into Dutch, so there is a patient advocate-led effort to create a new set of terms in Dutch.
- Roger raises concerns about implementation planning for the new nomenclature. One concern is around the possible impact on drug or diagnostic development and the other is about the kinds of communication issues covered in earlier episodes. Sven, who again worked more closely on the process, states with confidence that the change will not have an impact on drug or diagnostic trials. Subsequent events prove Sven right.
This conversation ties up several issues related to MASH and the new MASLD nomenclature that the panel did not touch on earlier in the episode. These range from the impact the nomenclature might have on other elements of treatment to the impact of this effort over time. Finally, the panelists grade the process to date (they admit, their views might be a bit biased) and signs of success.
Roger Green starts this conversation by asking what impact panelists believe the new MASLD nomenclature might have on NITs. From one perspective, Meena Bansal notes that it should have no impact given that NAFLD/NASH and MASLD/MASH map so similarly on top of one another. From a different perspective, Jeff Lazarus asks whether the nomenclature and accompanying guidelines from professional societies will result in more testing. The group aligns around the idea that patients living with Type 2 diabetes are an excellent target for increased testing with NITs given the high overlap of the two groups. Maru Rinella comments specifically that all efforts to tie T2DM to MASLD as frequently common metabolic diseases will be helpful and that discussing the proper use of NITs might be one way to make this connection. Louise Campbell agrees that increased focus on "Healthy Livers, Healthy Lives" will drive exactly these kinds of discussions. The rest of the episode consists of Roger asking panelists three questions, to which they respond:
- What might change over the next year or two? Meena believese that approval of a drug will drive significant growth in the learning curve and, with that, enhanced disease awareness and understanding. Jeff suggests that this will not take the form of a transition from NAFLD to MASLD, but instead that people first learning about the disease will use the new nomenclature properly. Mike Betel notes that on the Fatty Liver Alliance website, ~98% of searches are simply for "fatty liver disease." Over time, he anticipates this will change and also that websites like FLA will address "fatty liver" queries in terms of new nomenclature.
- Impact on ICD codes. Meena, who is doing significant work in this area, answers that the goal is to have no impact but simply a smooth cutover.
- How the group would grade its work on this activity to date. As Jeff notes, answers from the people who led the process are likely to be quite biased, but all gave fairly high grades.
This conversation focuses on how the new MASLD nomenclature might improve providers' explanations of MASH to patients. Louise Campbell describes new opportunities, while Meena Bansal describes how focusing on metabolism provides a richer opportunity for providers to explain to MASH patients why fat on the liver matters.
Louise Campbell starts this conversation by discussing a new NHS program providing primary care centers with VCTE units they can use to screen patients for MASLD and MASH. She points out that this will provide a unique opportunity to present the new MASLD nomenclature to primary care and allied health providers in a way that connects immediately to diagnosing patients and educating them properly about their disease. She notes that at the patient level, the discussion is still likely to focus on excess fat on the liver but presents the idea of "fat" in a less stigmatizing way.
Meena Bansal focuses more specifically on exactly how provider-patient conversations might change. For years, she suggests, physicians have written "hepatic steatosis" on patient charts, but then told patients they "just have a little fat on the liver." In her view, the new nomenclature will take the word "just" out of the discussion and present the "little fat on the liver" as part of a metabolic syndrome that requires treatment. She goes on to mention another source of excitement: the ability to consider MetALD patients as part of the same MASLD community and add them to Mt. Sinai's longitudinal patient registry, which will likely become a rich source of MetALD data.
Earlier in the episode, Jeff Lazarus had mentioned his excitement at the growing role and publicity for the "Healthy Livers, Healthy Lives" initiative. Louise notes that increasing focus on liver awareness and awareness of the importance of liver health, as discussed in Season 5 Episode 2, aligns neatly with Meena's disease description and the new communication opportunities for new physician and allied health specialties.
This conversation shifts from the rearview to the path ahead. Louise Campbell starts by asking about the role of Allied Health Providers in the process. After this issue, process leaders Maru Rinella, Jeff Lazarus and Meena Bansal discuss how this will roll out as we move ahead.
It starts with Louise Campbell asking why there Allied Health Providers did not play a larger role in the Delphi process. Maru Rinella replies that, in her vision, this group’s involvement will be critical in the rollout and message development but less so in a Delphi process that was mostly about hashing out, as Maru puts it, “the nuances of the disease.” To Maru, this is also the place where patient voice brings the most pivotal value. Meena Bansal notes that there were some PAs and NPs in the Delphi process. Meena Bansal agrees that their role will be critical in discussions on how to communicate the disease to the patient (a topic we return to in later conversations). Louise appreciates, accepts and largely agrees with this discussion.
Roger Green shifts focus from the past process to ask about the rollout phase: when it began, what it will include and when it might end. Meena says it will never end. Jeff Lazarus comments that while publication was the formal rollout, even before then groups were vying to be the first to change their names. He also noted that the article was published simultaneously in several journals with broad, rapid uptake in the literature. Since the key is to raise awareness and educate the population, he considers the speed and breadth of uptake a major sign of success. Maru Rinella comments that journal participation has been generally excellent.
This conversation focuses on the Delphi process for a new MASLD nomenclature. It starts with Jeff Lazarus describing what a Delphi process is and how it worked here. Jeff and two other key players in this process, Maru Rinella and Meena Bansal, describe what they consider some of its greatest strengths as well as one thing they wish had worked out better.
Jeff's description focuses on the four rounds of data gathering and some key activities that transpired before the formal process began. He goes on to identify what he considers some of the pivotal outputs of this one. In particular, Jeff describes the focus on patients with alcohol and diet issues, and the naming of a new discreet disease for these patients (MetALD) as being “revolutionary.”
Roger Green agrees with Jeff's assessment that the naming of MetALD was an important outcome and that the process had clear benefits in this way. He goes on to ask why people opted out of the process. Maru Rinella comments that some people opted out after the third phase due to disagreements with the direction of the activity. Roger refines the question to ask why people opted out in the first place. Jeff and Maru note the amount of work required for this kind of activity, and he, Maru Rinella and Meena Bansal all describe that not all invitees understood how important this process would be upon first invitation. Jeff and Maru go on to mention that the participation rate was high, somewhere around 80%.
Roger asks what could have gone better. Maru, Jeff and Meena Bansal each note groups for which they wish participation had been broader, including possibly a broader representation of stakeholders (notably, more patients, although Maru notes this was not for lack of trying) and more organizations or countries.
This conversation focuses on the issues and visions that led to the identified need for a new MASLD nomenclature. Maru Rinella and Jeff Lazarus discuss the original goals of the process and how focus broadened and shifted throughout.
It starts with Maru Rinella describing what she terms “an existential crisis” for the field around a publication suggesting changing the name of the disease from “non-alcoholic” fatty liver disease to “metabolic” fatty liver disease. She considers this the main impetus for key global players to converge. Jeff Lazarus notes that stigma and several other processes came into the discussion. Maru and Jeff agree that the participant recruitment process came in two phases, one where it was hard to get participants and a later point where it was to manage the size of the exercise. Jeff felt the tipping point happened when people understood how the Delphi process would work and also the need for this to succeed. Maru felt that people had to grasp the implications of a consensus process, which Delphi is. As the conversation ends, another leader in the process, Meena Bansal and a patient advocate participant, Mike Betel of the Fatty Liver Alliance, describe how they came to enroll.
The process of creating a new MASLD nomenclature for the condition formerly known as Fatty Liver Disease was a multi-year process with unique challenges and complications. Three leaders in the process, Maru Rinella, Jeff Lazarus and Meena Bansal, and patient advocate Mike Betel join Louise Campbell and Roger Green to discuss the process, transition and rollout.
00:00:00 - Surf's Up: Season 5 Episode 3
Co-hosts Louise Campbell and Roger Green sit with Maru Rinella, who co-chaired the New Nomenclature process, Jeff Lazarus, who oversaw the entire Delphi process, Meena Bansal, who played a key role and co-moderated the 2023 AASLD session, and patient advocate Mike Betel to discuss the entire process from inception to today and beyond.
00:03:57 - Meet Meena Bansal
Dr. Meena Bansal, Division Chief at Mt. Sinai Hospital in New York, discusses how she became involved in liver disease and her current research interests, and shares one fact about herself that might surprise you.
00:05:47 - Groundbreaker
Panelists share one piece of good personal or professional news from the previous week.
00:08:22 - Characterizing the Nomenclature Process
Maru and Jeff discuss the original goals of the process and how focus broadened and shifted throughout.
00:16:02 - How the Delphi Process Worked
Jeff describes the overall process. Roger asks about people who chose not to participate at the outset, which leads to a discussion about the overall rate of participation. Roger then asks what might have worked better, which leads Maru, Meena and Jeff to discuss groups they wish had been better represented.
00:27:05 - The Role of Allied Health Providers
Louise asks why Allied Health Providers did not play a larger role throughout the process. Maru and Meena differentiate between providers' roles in the early process and the mechanics of rolling out to the patient community.
00:29:38 - Focusing on the Rollout
Roger's question about the rollout leads Jeff to focus on some of the key early stage events. Jeff and Maru go on to discuss the high level of participation from key journals.
00:33:32 - Early Awareness
Mike Betel brings a piece of data on physician awareness from the pre-test of a study he is conducting in Canada, which serves as a conduit into the entire topic of who is aware of the nomenclature today and how knowledge will spread over time.
00:38:56 - The New Message for Patients
Louise notes that the upcoming UK effort to bring VCTE screening to primary care will provide an effort to define and characterize the disease for patients. Meena comments that providers have done this informally for years, but while the message used to be that the patient "just has fat on the liver," this nomenclature will formalize the disease, remove "just," and focus the patient on therapy.
00:39:15 - MetALD - A New Disease in the SLD Family
Roger states that in his mind, the newly defined disease MetALD is a major positive outcome of the process. Maru, Meena and Louise each describe ways this new definition will aid diagnosis and treatment, Mike notes that the message still must be tailored for each patient.
00:43:55 - Implication for Diagnostics
The group discusses the idea that while the nomenclature will not lead to new diagnostic tests, it might lead to increased and more appropriate use of the tests that exist.
00:48:25 - The Future of the Nomenclature
Roger asks the group where this process will be in a year and five years. Answers vary.
00:51:58 - Grading the Process So Far
Roger asks panelists how they grade the process to date. Grades are high although, as Jeff notes, they are grading their own work.
00:55:27 - Business Report
News on audience metrics, the upcoming Question of the Week, next week's epidemiology discussion and this week's Vault conversation
This conversation is part of a March, 2023 interview between co-hosts Louise Campbell and Roger Green and Jeff McIntyre of Global Liver Institute, one of the guests on the S5 E2 panel. This particular conversation focuses largely on Jeff’s insights around the imminent anticipated drug approvals of obeticholic acid (which was withdrawn several months later) and resmetirom (whose PDUFA date is next month).
Jeff's analysis includes mixed levels of enthusiasm around a draft report from ICER which includes pricing estimates for these drugs. The contention lies in the draft’s reference to NASH as a non-progressive disease - a position which the panelists readily refute. Jeff’s positive note is that the report carefully considers patient perspective and he was able to participate as an expert reviewer.
The conversation shifts to speculations around the future standard for noninvasive testing and biomarkers. Jeff emphasizes the “need for a noninvasive that can be scaled with the least amount of burden to primary care providers and the patient populations that need them.” Roger Green points to the various guidelines’ referral to FIB-4 as such a test. This summons quote of Quentin Anstee's repeated admonition that “we not let the perfect be the enemy of the good.” For whatever shortcomings of FIB-4, if it can be done now and it's two generations of successive approximation of what we've had before.
As the session winds down, Louise Campbell asserts further comments around the ICER draft and NASH as a progressive disease. She recollects the podcast’s recent conversation with Tim Jobson, founder of Predictive Health Intelligence, (S4 E5) which discusses developing a simple tool to identify patients at risk of liver disease by analyzing the results of blood tests given throughout their lives.
Leading MASLD patient advocates Jeff McIntyre (Global Liver Institute), Milan Mishkovikj (European Liver Patients Association), Tony Villiotti (NASH kNOWledge) and Wayne Eskridge (Fatty Liver Foundation) describe their respective organizations' priority 2024 MASH programs to co-hosts Louise Campbell and Roger Green.
In this conversation, the advocates each describe their respective organizations' top project for 2024. Wayne Eskridge goes first, describing the Fatty Liver Foundation's annual "flagship" study, The State of NAFLD and NASH Care in America. This study, which has been going on for "a few years," surveys patients' experiences around diagnosis and treatment of their SLDs. This year, which increased focus on non-invasive testing and the anticipated availability of a MASH drug, should yield particularly interesting results. Tony Villiotti talks about the extensive "liver awareness" education work NASH kNOWledge is conducting with over 250 schools and community centers in the Pittsburgh area. As part of NASH kNOWledge's ongoing effort to communicate to children on their own level, Tony anticipates his 10-year-old grandson accompanying the team this year, dressed in a "Livvy the Liver" costume. Milan Mishkovikj discusses a program where ELPA leadership conducts liver screenings at the European Parliament in Brussels, which provides opportunities not only to teach legislators and executives about their liver disease but also to learn their own liver health status. Jeff McIntyre discusses GLI's Advanced Advocacy Academy, or A3, a program to create and educate liver health advocates across the globe. To use Jeff's phrase, the program is starting to "grow roots" and become a self-sustaining year-round activity. Louise Campbell notes that the common theme in all four programs is that they are patient-focused, and most are children-focused.
Roger's final question is to ask what will constitute success for each organization over the next 12 months. The answers vary in specifics but carry the basic themes of education, access and drug approval common to the rest of the conversation.
Leading MASLD patient advocates Jeff McIntyre (Global Liver Institute), Milan Mishkovikj (European Liver Patients Association), Tony Villiotti (NASH kNOWledge) and Wayne Eskridge (Fatty Liver Foundation) join Louise Campbell and Roger Green to explore the roles advocacy groups might play in supporting patient access through drug information, education and advocacy processes.
The conversation starts with Roger. He takes note of advocates' sense that they are held outside the access process and asks whether and how that might change. Wayne suggests the question itself is highly optimistic, noting that in a fragmented payer structure, the only advocate organization large enough to have impact is GLI, and he commends them for doing so. Louise comments that while patients take the medications, "they are not the market. The market is the payer." In the UK, the market is either NICE or the private insurers, and these payers look for cost effectiveness. She also notes that MASH drugs might find themselves competing against diet and exercise, incretin agonists and other interventions yet to come that are not steatosis-specific. Prescribers make decisions within the context of guidelines (what Louise describes as "ticking boxes").
Tony notes that payers are the "final frontier" in terms of communicating with patients and assessing their needs. Jeff notes that this range of access-related issues are what he described earlier as the "second half" that starts subsequent to drug approval. He notes that in the US, this relates not only to private insurers but also CMS and the VA system, since most of the early MASH patients will be older than 65. He views patient activism and advocacy as the vehicles patients can use to affect the value process and achieve wider, simpler availability to medications. Milan looks at these same questions from a European perspective, and notes that government payers care about total cost of disease. For MASH, this probably involves liver cancer more than any other disease sequel.
As the conversation ends, Roger comments that in his past work as a pricing consultant, he always advised clients that education and communication were keys to long-term success. In his vision, a patient who does not see the value in medication will not take it. This will lead the prescriber to believe it doesn't work well and, over time, not to prescribe it.
Leading patient advocates Jeff McIntyre (Global Liver Institute), Milan Mishkovikj (European Liver Patients Association), Tony Villiotti (NASH kNOWledge) and Wayne Eskridge (Fatty Liver Foundation) join Louise Campbell and Roger Green to discuss what Jeff calls "the second half" - the hard work on coding and patient access that will follow the first MASH drug approval.
Leading patient advocates Jeff McIntyre (Global Liver Institute), Milan Mishkovikj (European Liver Patients Association), Tony Villiotti (NASH kNOWledge) and Wayne Eskridge (Fatty Liver Foundation) discuss their expectations for life after the resmetirom PDUFA data and, with it, the potential for the first MASH drug approval, with Louise Campbell and Roger Green.
The conversation starts with Roger noting a funny coincidence; the March 14 PDUFA data for resmetirom is Pi Day, which means the first MASH drug approval might come on the math geek's favorite day of the year. He asks panelists to describe their moods as they look forward to the event. All five other panelists Advocates describe their "guarded optimism" regarding whether resmetirom will be approved. Wayne Eskridge also notes the potential for confusion and disappointment because not every patient who anticipates receiving the new drug will do so. Louise Campbell and Milan Mishkovikj describe how US approval might affect their respective countries and regions. Going last, Jeff McIntyre describes the extensive planning GLI is doing to prepare for a PDUFA decision that might raise as many questions as it answers, particularly around coding, reimbursement and definition of appropriate patients. When he has finished discussing the questions we might all face arouind the initial FDA ruling on resmetirom, he goes on to describe a possible approval path for countries outside the US.
00:00:00 Surf's Up: Season 5 Episode 2
Co-hosts Louise Campbell and Roger Green sit with four leading MASLD patient advocates (Tony Villiotti of NASH kNOWledge, Wayne Eskridge of the Fatty Liver Foundation, Jeff McIntyre of the Global Liver Institute, and Milan Mishkevikj of the European Liver Patients Association) to discuss their plans and actions for MASH patients in 2024. The discussion covers the advocates' hopes and concerns for the year and the programs and efforts each considers top priority.
00:04:09 Meet Milan Mishkovikj
North Macedonian patient advocate Mishkovikj, a key leader in the ELPA, discusses how he became involved in liver patient advocacy and shares one fact about himself that might surprise you.
00:11:25 Groundbreaker
Panelists share one piece of good personal or professional news from the previous week.
00:15:52 Anticipating Pi Day
Every year, Pi Day is March 14. This year, that date has extra significance: the PDUFA Date for resmetirom approval at FDA. Advocates describe their "guarded optimism" regarding whether resmetirom will be approved. Wayne notes the potential for confusion and disappointment because not every patient who anticipates receiving the new drug will do so. Louise and Milan describe how US approval might affect their respective countries and regions. Jeff describes the extensive planning GLI is doing to prepare for a PDUFA decision that might raise as many questions as it answers, particularly around coding, reimbursement and definition of appropriate patients. He also describes a possible approval path for countries outside the US.
00:26:42 Post-Approval Planning
As Jeff puts it, "We have to be planning for the second half while we're playing the first half on this," with essential questions about the implications of labeling on the topics he mentioned earlier. Roger asks what role patients might play in access decisions, to learn that the advocates have largely been "blocked out" of the process. GLI anticipates driving conversations with health systems around policies and access. The other US advocates do not anticipate doing so. Milan describes how ELPA will work with EMA, the European Parliament and other relevant groups. Louise adds private insurers and governmental payers to the critical post-launch lobbying and discussion targets.
00:38:43 Where Does the Patient Fit?
Roger asks where patients fit in the decision paradigms and how that might change over time. Louise shares her view that while patients might consume the medications, the real customer is either the prescriber or payer. Tony describes payers as "the last frontier" in learning how patients feel. Jeff returns to a range of "here and now" access issues GLI can address now. Milan and Roger discuss perspectives on the interplay of regulators, payers, providers and patients.
00:49:13 Advocates' Key Programs
Each advocate describes one key program they will run in 2024. Wayne describes FLF's State of NASH Care in America survey. Tony describes NASH kNOWledge's children's education programs. Milan describes continuing pilot programs ELPA started in 2023 to education the European Parliament. Jeff discusses GLI's Advanced Advocacy Academy, which "grew roots" worldwide in 2023. At different points earlier in the discussion, each advocate commended the support they get from GLI.
00:56:30 Closing Question
Roger asks what will tell each advocate whether they've been successful when they look back on 2024, 12 months from the recording date. Answers are powerful and vary by organization.
01:02:55 Business Report
News on audience metrics, the upcoming Question of the Week, next week's nomenclature discussion and this week's Vault conversation.
After a month off in January, SurfingMASH returns for the 2024 calendar year. In this last segment of Episode 1, the co-hosts explore the complexities surrounding advertising and accessibility of metabolic agents in the US market, with a particular focus on how these factors might influence public engagement and healthcare provider education.
The tone of this segment demonstrates concern that gaps or inaccuracies in consumer information might affect patient treatment in the care pathways, as providers who may not yet be equipped to handle inquiries about newly approved liver treatments deal with issues of proper prescribing and access.
Louise Campbell starts this conversation by reflecting on the challenges and frustrations caused by price and access disparities when DAAs entered the Hepatitis C market. In her UK practice, native Egyptians went back to Egypt to purchase DAAs at £1,000, which meant that the UK care team lost control of patient information. She highlights the importance of educating not just physicians but also allied health professionals who spend more time with patients, to ensure they can have informed discussions about new medications and their management. She proposes exploring education strategies and designing clinical pathways to support the effective introduction of new treatments. She mentions upcoming recommendations for fatty liver in Australia as an example of progress in liver health management.
Roger Green expresses interest in delving into diagnostics challenges, especially considering the rapid uptake of semaglutide and tirzepatide as weight loss drugs offered by telemedicine providers outside the traditional care paradigm. He worries about the potential this model has to leave treaters with inadequate or inaccurate knowledge of their patients, and advocates for a more educated approach by payers to include liver-aware diagnostics in metabolic disease management to better serve patient needs and prevent liver-related complications.
Jörn Schattenberg also advocates for broader, deeper education campaigns while noting that there appear to be few if any interactions between GLP-1s and resmetirom based on clinical trial reports.
This conversation underscores the interconnected challenges of drug marketing, healthcare provider education, and diagnostic practices in the evolving landscape of liver treatment and highlights the need for a multifaceted approach to address these issues effectively.
After a month off in January, SurfingMASH returns for the 2024 calendar year. In this conversation, the group examines the explosion of telemarketer-driven consumer advertising for GLP-1 agents as anti-obesity medicines and asks what impact this might have on diagnosis, treatment and monitoring of MASH in the US.
Specifically, the participants discuss the potential impact and concerns surrounding the use of weight-loss drugs, including semaglutide, and the impending approval of drugs for treating fatty liver disease. They highlight the challenge of ensuring patients receive comprehensive care that includes liver health assessments, especially with the rise of telemedicine and commercial approaches to medication distribution. The dialogue underscores the necessity of educating healthcare providers beyond physicians, such as Allied Health professionals, to have informed discussions about these medications and their management.
The discussion also delves into the issues of drug pricing, the black market for medications, and the importance of proper education for all healthcare providers to prevent misuse and ensure the right patient populations are being treated. Jörn Schattenberg notes the significance of preparing for drugs that are weight neutral, addressing the obesity epidemic without exacerbating liver disease issues. He emphasizes the need for specialists to assess treatment responses and manage patient care effectively.
Roger Green expresses concerns about the commercialization of healthcare leading to suboptimal patient education and care, particularly in the context of obesity treatment. He plans to engage with payers to discuss the implications of new treatments on healthcare systems.
Louise Campbell raises questions about drug-drug interactions and the broader implications of new treatments being prescribed outside their intended patient populations. Jörn reassures that no major issues were identified in clinical trials regarding drug-drug interactions and believes that standard clinical practices can manage any potential concerns.
The conversation reflects a complex landscape of treating liver and obesity-related conditions, highlighting the need for comprehensive education, careful patient assessment, and a multidisciplinary approach to healthcare in the face of new and emerging treatments.
After a month off in January, SurfingMASH returns for the 2024 calendar year. In this conversation, the group explores the goal of provider and patient liver education, key goals for liver awareness and the potential for direct-to-consumer advertising of GLP-1s for weight loss to garble the "liver awareness" message.
The dialogue underscores the concern that the convenience of telemedicine and the allure of easily accessible obesity treatments might lead patients to overlook comprehensive health assessments, especially for liver disease. The conversation reveals a broader concern about the health system's ability to ensure that treatments like Novo Nordisk's weight loss drug are used responsibly and with proper medical oversight.
Louise emphasizes the importance of being "liver aware" and advocates for integrating liver health into overall health assessments. She suggests that everyone, especially those prescribed weight loss medications, should have basic liver function tests to identify any underlying liver conditions that could be exacerbated by such treatments. The discussion also touches on the dangers of the black market and non-prescribed use of weight loss drugs, highlighting the need for education and responsible prescribing practices.
The conversation shifts to the potential impact of drug approval publicity and the need for health systems to educate both patients and healthcare providers on the comprehensive management of obesity, including liver health considerations. The speakers express concern that the hype around new treatments could overshadow the importance of holistic health assessments and lead to missed opportunities for diagnosing and treating liver disease.
After a month off in January, SurfingMASH returns for the 2024 calendar year. In this conversation, Louise Campbell describes how VCTE can serve as a behavioral monitor, Roger Green reviews some changes in the podcast this year and the group begins to discuss why "liver awareness" should become an important concept.
As this conversation starts, a joke from Roger Green about "VCTE as lie detector" leads Louise Campbell to note that personal trainers should consider looking at "internal health" (fat in organs) instead of "external health" (general obesity). She also discusses the ability to link her digital app, MyLife365.me, to VCTE measurements.
Roger Green becomes the last co-host to discuss his last couple of months. He outlines a couple of upcoming changes in the SurfingMASH podcast, including a new "Question of the Week" segment.
After describing the new segment, Roger shifts the conversation to focus on some practical issues surrounding the potential for increased demand on the clinical care pathway once a MASH drug is approved. Jörn Schattenberg notes that we will need dramatic increases in provider education over time for them to step into an active role in the pathway. He believes that drug approval will speed this process.
Throughout the entire episode, a question re-emerges about the goal of liver education. In the past, this podcast has discussed "liver health" and "liver wellness" as if the liver is the target and goal. In this conversation (and later in the episode) the concept of "liver awareness" bubbles up. "Liver awareness" refers to appreciation of the role the liver plays in all metabolic health.5
After a month off in January, SurfingMASH returns for the 2024 calendar year. In this conversation, Louise Campbell describes her recent efforts in enhancing liver health awareness and education, focusing on the launch of the user-friendly website MyLife365.me. Also, she shares lessons about patient communication and creating liver awareness.
This conversation combines an informal discussion on best ways to deliver information to patients with some more formal thought about good communication. The website's significant increase in visitor metrics indicates a growing public interest in tracking one's own liver health. while expansion and uptake in multi-lingual and non-English-speaking countries suggests its versatility. Louise highlights the importance of easy-to-understand resources, such as color-coded interpretations of diagnostic results, which have made liver health information more accessible to the general public.
On issue at the outset: despite the adoption of new medical nomenclature, she notes the public's continued use of traditional terms like "fatty liver" when seeking information.
She also shares the expansion of her MyLife365 app to countries including India and France, providing users a platform to track liver health improvements through lifestyle changes. The app's feature of visualizing liver health progress in a simple and engaging manner has been particularly well-received, fostering liver health awareness among younger demographics. Jörn contributes to the conversation by emphasizing the benefit of detaching liver health from stigmatizing factors like body weight, focusing instead on pathophysiological relevance.
The dialogue shifts to the practical applications of liver health tracking in clinical settings. Louise mentions the positive feedback from both patients and physicians on the convenience and effectiveness of using the app for monitoring liver health over time. The discussion underscores the importance of being "liver aware," promoting preventive health measures, and facilitating conversations about liver health in both clinical and everyday settings.
This conversation reflects a broader shift towards engaging the public in proactive liver health management, leveraging technology and clear communication to demystify liver disease and encourage healthy lifestyle changes. Louise's initiatives, including the website and MyLife365 app, represent significant strides in liver health education, aiming to bridge the gap between clinical knowledge and public awareness.
After a month off in January, SurfingMASH returns for the 2024 calendar year. In this conversation, Jörn Schattenberg describes the challenges, opportunities and experiences that he has found in assuming Department leadership at the University of the Saarlandes.
Jörn shares his early experiences and aspirations as the new chair of a department, emphasizing the joys and challenges of transitioning into this leadership role. He lists the department's strengths and identifies
opportunities for growth based on his own prior experiences.
Jörn provides specific focus on his aim of enhancing clinical trials and diagnostic capabilities within the department. He discusses the importance of building a clinical study team and ensuring that physicians have the support and time needed to engage in patient recruitment for clinical trials.
Separately, Jörn highlights innovative patient navigation systems already in place at Saarlandes, like the pager system that enables patients to move from appointment to. appointment within the hospital seamlessly. He discusses his desire to streamline outpatient diagnostics and improve collaboration with the radiology department for advanced imaging techniques. Jörn's approach is patient-centric, focusing on better treatment options and diagnostics, and he has received positive feedback from colleagues.
The conversation underscores the significance of leadership in driving clinical and administrative improvements, fostering a collaborative environment, and enhancing patient care through innovative practices and a focus on liver diseases.
The first episode of Season 5 of Surfing the MASH Tsunami starts with a brief discussion of what the co-hosts have worked on for the last two months and proceeds to consider the impact on patient treatment of having a MASH drug approved in the US market, particularly in today's direct-to-consumer weight loss advertising.
The conversation starts with Jörn Schattenberg discussing his first two months as a Department Chair, focusing on the transition, challenges, and opportunities he has encountered. He focuses on the satisfying challenges and opportunities he's encountered, including managing inpatient departments and enhancing the department's focus on liver-centric research and clinical practices. Significant emphasis is placed on improving diagnostic capabilities and clinical trials, highlighted by securing two major EU grants for liver disease research.
Louise's talk focuses on the launch of a new, user-friendly MyLife365.me website aimed at improving liver health. The revised website is generating major growth in traffic and has expanded beyond the world's major English-speaking marketing to France and India. Louise highlights the app's success in engaging both the general public and physicians, which can facilitate easier discussions about liver health with physicians and patients sharing easy-to-interpret, color-coded outputs.
Roger briefly discusses some of the changes coming to this podcast in 2024. One exciting element is the new "Question of the Week" segment, which is scheduled to launch later this month.
The rest of the discussion centers around some practical patient treatment issues that might arise upon the approval of a MASH drug (presumably resmetirom, coming later this year). Some of the discussion focuses specifically on increased needs for patient identification and screening that will arise with increased consumer public relations and physician education. Roger expresses a concern that increased consumer advertising for telemedicine and local medical practices that center around prescribing semaglutide or tirzepatide over the phone will create an array of challenges for patient screening and management (possibly even accurate record keeping). The group agrees that increasing the depth and breadth of education will be one key to success, including a broadening of targeted specialties and, as Louise points out, different provider groups.
Surfing the MASH Tsunami continues its 2023 wrap-up conversations with Global Liver Institute Vice President of Liver Health Programs Jeff McIntyre, along with co-hosts Louise Campbell and Roger Green. The conversation focuses on Jeff's mixed assessment of 2023, focusing largely on drug approvals and the new nomenclature.
In 2023, the field of fatty liver disease experienced both setbacks and progress, encapsulated in Jeff's phrase, "Two steps back, one step forward." Central issues included drug approval processes, nomenclature changes, and advancements in understanding and treating Non-Alcoholic Steatohepatitis (NASH). The year was marked by significant efforts to address fatty liver disease, but results were mixed, partly due to the complexities and inefficiencies in the drug approval process.
A notable moment was the FDA Advisory Committee's review of obeticholic acid, which highlighted issues with the clarity and reliability of the FDA's drug approval endpoints. This process was perceived as bureaucratic, sometimes disheartening, and not always effectively engaging with patient communities. Jeff underscores the importance of enhancing communication between various stakeholders in healthcare, including medical societies, patient communities, and regulatory bodies.
The conversation also reveals a consensus on the need for more involvement of patients and nurses in decision-making processes. Jeff stresses the necessity of educating the FDA about liver disease and the impact of drug approvals on patient safety, advocating for a stronger voice for patients and nurses in redefining the FDA’s approach to safety.
Roger adds to the discussion by expressing concerns about institutional risk aversion in regulatory processes, which can impede drug approvals. He points out that some FDA committee members lack basic knowledge about fatty liver disease, leading to naive questions and decisions. Louise highlights the reclassification of fatty liver disease as metabolic dysfunction and its potential benefits, suggesting that integrating liver disease treatment within endocrine and cardiology care could be beneficial due to the interconnected nature of these fields.
Looking ahead to 2024, Jeff anticipates positive developments in drug approvals and increased patient involvement. He notes the change from International NASH Day to Global Fatty Liver Day, indicating a shift in nomenclature and expectations of more patient engagement in regulatory discussions and decision-making processes.
In conclusion, the conversation reflects a blend of optimism and caution regarding the future of fatty liver disease treatment. The importance of patient-centered approaches and collaborative efforts among healthcare stakeholders is emphasized, highlighting the ongoing need for patient advocacy organizations to play a significant role in navigating the complexities of the disease. This includes dealing with the challenges posed by the new nomenclature and the potential for new treatments. The dialogue underscores the necessity for a more integrated, patient-focused healthcare system that prioritizes the perspectives and needs of those directly affected by fatty liver disease.
Surfing the MASH Tsunami continues its 2023 wrap-up conversations with Ukraine Public Health Executive Tatiana Deshko, Mike Betel of the Fatty Liver Alliance and co-host Roger Green. The conversation focuses on how the last six months of the Ukraine war have affected public health challenges and citizen morale and how continuing foreign aid from the US and Europe affects that morale.
This conversation focuses on how the last six months of war have affected citizen morale and, concurrently, an evolving and increasingly challenging healthcare landscape. The conflict continues unabated, causing substantial loss of life, disrupting daily routines, and imposing severe strains on the healthcare system. Despite the hardships, Tetiana explains, the Ukrainian people remain steadfast in their commitment to freedom and democracy, even as they face exhaustion and depleted resources.
The healthcare crisis that Tetiana outlined in Season 4 Episode 28 has escalated due to the rising number of wounded and, concurrently, an acute shortage of human resources to address the expanding health needs. The number of available healthcare professionals keeps diminishing as many have been called to military service.
To counter these challenges, Ukraine has pivoted towards innovative solutions, including telemedicine and artificial intelligence. These technologies play a crucial role in offering health advice, particularly for chronic conditions such as HIV, hepatitis, and tuberculosis. They help by simplifying patient pathways, expediting diagnostic processes, and ensuring timely treatments in a resource-constrained environment. But while international support for telehealth initiatives is significant, \ language barriers remain a substantial challenge to effective care delivery.
The ongoing conflict complicates the ability to address non-urgent health issues like metabolic diseases. The war has also led to a surge in stress-related diseases, mental health issues, and suicides, especially among the youth in urban areas. All this leads to declining health attention and general health among Ukrainians.
This conversation underscores the dire situation in Ukraine, where the healthcare system struggles constantly to adapt to the demands of war. There's a pressing need for mental health support and an increase in stress-related illnesses. Telemedicine has become a critical tool for connecting displaced patients with healthcare providers. However, language barriers and the vast healthcare needs present formidable obstacles.
These war-related challenges to Ukraine's healthcare system are profound. The dedication and resilience of healthcare professionals like Tetiana are pivotal, but the entire system also relies on vital support from the international community. International support is particularly key in certain inventive healthcare delivery solutions, including implementation of mobile clinics and efforts to establish prosthetic centers. These challenges are particularly acute in occupied territories, which lack healthcare infrastructure. Additionally, new warfare tactics like the use of mines and tear gas have introduced further complications, increasing the need for specialized care and support, including for blinded veterans.
Despite these difficulties, there is an enduring spirit of resilience and resourcefulness. The Ukrainian people and healthcare professionals keep adapting to these unprecedented challenges, showing remarkable ingenuity in finding solutions. While the road ahead is fraught with complex obstacles, there is hope that the current turmoil will lead to development of a more robust and resilient healthcare system in Ukraine. The continued commitment to a free and democratic Ukraine, boosted by innovative healthcare strategies and backed by international support, underscores the nation's determination to overcome these adversities.
Surfing the MASH Tsunami continues its 2023 wrap-up conversations with Novo Nordisk International Medical Vice President Michelle Long, along with co-hosts Louise Campbell and Roger Green. The conversation focuses on advances in research, collaboration and insight creation the entire MASLD research community has made in 2023 and what this new perspective portends for the future of MASLD research.
Michelle starts by using the word "momentum" to characterize the MASLD research community in 2023. She says the pace of change makes it impossible to summarize or describe the year easily, For example, the adoption of new nomenclature came six months ago at EASL, but it feels like it was far longer than that. Roger compares the optimism in the field to 2019 while awaiting what was the anticipated approval of OCA. Today, he notes, the entire community understands so much more about MASLD and has so much more confidence in resmetirom than in OCA that we see optimism about future drug developments along with a greater appreciation of the potential scale of the global crisis around MASLD.
Michelle comments that in the aftermath of OCA, the scientific community has been "willing to adapt and eat humble pie." Today, we see proposals for future studies that demonstrate how fast researchers are adopting new knowledge and using it in new study designs. In particular, she notes that the year's FDA workshop showcased a shift in drug development strategies and a deeper understanding of surrogate endpoints, reflecting a desire within the field to embrace new insights for advancement.
Louise adds to the dialogue by discussing the swift adoption of new terminology and the integration of noninvasive diagnostic technologies, emphasizing the patient's perspective and the importance of comprehensible communication about their health condition. She advocates for broader inclusivity in future Delphi processes, specifically seeking greater involvement for nurses and allied health professionals, groups that provide line communication with patient communities.
Roger notes a newfound humility within the academic medical community that promotes collaboration and ongoing improvement. Michelle agrees, stressing the need to dismantle barriers such as pride and the critical role of cross-sector collaboration in addressing the field's unmet needs and the lack of approved therapies. She designates 2023 as a turning point, with a shift toward a more open, conservative, and cooperative mindset in the scientific community, departing from previous attitudes.
The discussion moves to the intricacies of interpreting histology data from clinical trials, where Michelle points out the importance of a nuanced understanding of such data, including the timing of biopsies and the correlation with noninvasive testing results.
As an example of the new nuances, Roger cites bariatric data shared at EASL suggesting that it takes five years for the liver fat reduction associated with bariatric surgery to translate into a one-level regression of fibrosis and a HistoIndex study suggesting a consistent "true" placebo rate of 34%, which is far higher than we see in drug studies. Michelle acknowledges that aligning the ideal scientific method with business realities is a pivotal, realistic challenge. The group concludes with predictions for 2024, expecting significant advancements, possibly including new therapy approvals. Despite potential obstacles, there is a shared optimism for rapid progress and enhanced collaboration in hepatology research and clinical practice.
Surfing the MASH Tsunami continues its 2023 wrap-up conversations with biotech entrepreneur Rachel Zayas, Founder and CEO of AGED Diagnostics, along with co-hosts Louise Campbell and Roger Green. The conversation focuses on AGED's progress in 2023, what Rachel has learned about fundraising and creating winning pitches, and what she anticipates for her company and the entire MASLD community in 2024.
The discussion begins with Rachel, like most other participants in this series, highlighting the FDA decision on resmetirom, anticipated by March 14, 2024, as a breakthrough event for the MASLD community. She expects this will lead to a breaking down of traditional silos between medical fields, fostering a more integrated approach to healthcare. She already sees greater participation from other metabolic specialties in hepatology-related discussions and conferences.
Roger, intrigued by her comment, inquires about the specific forums facilitating this interdisciplinary engagement. Rachel responds that she sees small numbers of such specialists today but believes this foreshadows a growing trend.
The conversation then pivots to potential challenges facing the hepatology field in 2023. Roger asks Rachel whether she has seen any impact from the FDA's non-approvable letter for obeticholic acid on her segment of the investor community. Rachel states that the early-stage investors she courts assume high risk in their investments and, if anything, seem more likely to commit based on what the community is learning from burgeoning amounts of high-quality academic and commercial research.
Louise joins the discussion by highlighting the evolving landscape of healthcare investment. She emphasizes the significance of improved tracking mechanisms, noninvasive techniques, and adaptive FDA approaches. Louise advocates for a more inclusive approach in hepatology, suggesting increased participation in broader medical conferences to bolster interdisciplinary collaboration.
Turning to AGED Diagnostics, Rachel shares her team's advancements in research and development, particularly their work on a multi-site pre-clinical trial focusing on liver disease biomarkers. She outlines her team's objectives and expectations for the upcoming year, highlighting significant progress in their research endeavors.
The conversation also touches on Rachel's experiences with early-stage investors in the life science space. She notes their growing interest in hepatology, especially in noninvasive diagnostic tools for liver fibrosis and MASH. This shift in investor attention streamlines her pitching process, allowing her to focus more on developing AGED's technologies and solutions her team offers.
Looking ahead to 2024, Rachel anticipates the hoped-for resmetirom approval as pivotal. She also predicts an increased demand for noninvasive tools to monitor MASH progression and regression, foreseeing a rise in supply and demand for such tools once a therapeutic solution is available. She estimates that between 2025 and 2027, more tools in this area will emerge,
In closing, Roger asks about potential storm clouds and bright spots Rachel sees. She notes that payer approvals might constitute a logjam. Roger suggests that diagnostics that tell us which patients benefit from therapy will provide the best defense against such a logjam. In contrast, Louise suggests that the lack of education among allied health professionals might become another obstacle in implementing new treatments and diagnostics. She emphasizes the need for adequate frontline delivery systems to support the introduction of new medical solutions.
Surfing the MASH Tsunami continues its 2023 wrap-up conversations with Global Liver Institute Founder and CEO Donna Cryer, along with co-hosts Louise Campbell and Roger Green. The conversation focuses on Donna's personal health challenges in late 2023, what her absence revealed about the strength and depth of the GLI team, and what she foresees as major challenges for 2024.
The conversation starts with Donna discussing a major medical event in her life during the last few months in 2024, one during which, in her words, "I almost died." She speaks briefly but clearly about the nature of the event itself, as well as how and why she is rebounding to full strength. Donna goes on to describe how well the GLI team performed in her absence and the various forms of feedback she received confirming this. In response to a question from Louise, she notes that building a strong team has always been her priority at GLI and cites several past examples where the team has led while she assumed other roles and challenges.
From here, Donna notes a major change in 2023: the evolution from being a liver community to what she describes as "a community that cares about the liver," a multi-specialty, multi-stakeholder group focused on the wider implications of liver disease and patient and public health. As examples of this broader community, she cites the common guidelines from AACE and AASLD, conversations with payers and a willingness from other liver disease groups to share capabilities with the SLD community. She goes on to note that none of this change happens quickly, but that in the 10 years since GLI was formed, the scale of change has been consequential.
The discussion turns toward the process of nomenclature change. Donna notes her concern throughout the process that some important implementation steps were not being considered on as timely or thorough a basis as she would have hoped. Specifically, she cites the issue of ICD codes and the need to involve primary care providers and organizations into the key processes. Louise Campbell agrees, noting the challenges around bringing wider use of VCTE into the UK system even after NICE has accepted the need to do so.
Donna notes that this is the reason that GLI is calling its annual event Global Fatty Liver Day, not to be "recalcitrant, but because, as a global organization, we recognize" that not all parts of the world have adopted this nomenclature. She anticipates using what she calls "bridging documents" so that people using different nomenclatues can explain the same processes.
From here, the conversation transitions to cover the growing momentum and energy in the patient and advocate communities, as evidenced by general energy and Roger's experience (along with Mike Betel) of getting pushed out of overflow rooms for patient sessions at AASLD (listen to E50.2 for more details). Finally, the conversation returns to the value of the MetALD classification, some issues around Donna's recent health scare, and a promising view of the future.
Surfing the MASH Tsunami continues its 2023 wrap-up conversations with patient advocates Neeraj Mistry of the Fatty Liver Foundation and Jenn Leigh Jones of the Society for Sober Liver Survival, along with co-hosts Louise Campbell and Roger Green. The conversation focuses on the joining of their organizations and ways the new nomenclature affects how providers and patients look at Steatotic Liver Disease.
The conversation starts with Roger asking Neeraj and Jenn to provide a word of phrase that sums up the MASLD space at the end of 2023. Neeraj offers two words: "inclusivity and solidarity." "Inclusivity" refers to liver disease moving from being a "marginal issue" compared to other diseases to the center of the conversation. "Solidarity" refers to a commitment between providers, patients, corporations and advocates all to present a similar message based on the new nomenclature and the breadth of disease. Jenn's two-word phrase is "amor fati," a term coined by the Stoics and advanced by Nietzsche, meaning "love of one's fate." To Jenn, this means accepting one's past and learning from it. To convey this message, she tells her own story movingly, using the metaphor of a turtle.
Neeraj moves ahead to describe the patient experience as "many etiologies, one journey," and then to list the items that patients need on this journey: "care, support, treatment, access when available. And for those who are at risk, we need preventative intervention." For most liver diseases, he continues, the interventions are similar, sometimes identical. The new nomenclature creates a new, broad umbrella under which providers and advocates can create an "echo chamber" for common solutions. The new nomenclature provides this. Jenn adds that much liver disease results from mental health issues, regardless of the specific etiology. One of the sounds from the echo chamber needs to promote understanding of these issues.
Louise questions whether providers see the same inclusivity as patients and advocates. She cites her experiences in viral hepatitis, where providers tended to see patients from different geographic backgrounds or ethnicities as facing different challenges, and nurses as the patient advocates within the healthcare system to promote inclusivity.
Roger shifts to focus on stigma, specifically the idea that the counterpoint to inclusivity is the idea that people who feel stigma tend to look for someone suffering under greater stigma, which means that patients whose primary issue is alcohol look with disdain on those whose primary issue is diet, and vice versa. He adds that Hannes Hagstrom stresses the idea that all liver disease is on a spectrum (S4 E50.5). Neeraj notes that stigma and mental health challenges lead to habits that become addictions that become tremendously hard to overcome.
The discussion about stigma progresses in several directions: how it affects different stakeholders differently and the pivotal role of allied providers (Roger), how stigma represents a "tower of shame" and the importance of allied providers' empathy in overcoming shame (Jenn), the diverse skills and team treatment of mental health patients in NHS (Neeraj), and how viable models exist today (Jenn).
Roger notes that others in the system say that technology must be a pivotal part of the solution, given the lack of time available to doctors. Neeraj emphatically disagrees, noting that technology cannot be empathetic and that healing relies on interactions between people. Jenn concurs, noting that many patients in this system have relatively limited technological abilities or access beyond their cellphones.
The discussion closes with a question about 2024 and expressions of optimism and hope from the entire panel.
Surfing the MASH Tsunami continues its 2023 wrap-up conversations with hepatology researcher, key opinion leader and 2023 UEG Rising Star of the Year Hannes Hagstrom, along with co-hosts Louise Campbell and Roger Green. The conversation focuses largely on issues in diagnostics and clinical care pathways.
The conversation starts with Hannes describing highlights of 2023 as positive drug trials, excellent in-person meetings and the new nomenclature. Asked to clarify, he focuses on how the new nomenclature focuses on the interaction of alcohol consumption and what was previously called "non-alcoholic" disease. As a second point, he discussed the ability to use non-invasive tests (NITs) as a replacement for biopsy, if not entirely appropriate today, at some point in the near future.
Roger asks Hannes whether he has seen an impact of defining MetALD as a separate disease and including alcohol on the steatotic spectrum, he says he has not seen much yet, perhaps a little confusion about the new name (which he sees as necessary in any transition and appropriately timed now.
Roger asks Hannes whether he sees any "storm clouds" in 2023. Hannes sees two points for concern: the pace at which regulatory agencies acknowledge the value of NITs in diagnosis and early signs of confusion around clinical care pathways.
To Hannes, the entire community should prioritize simplification and streamlining to the degree possible. For example, primary care practitioners (PCPs) will send diabetes patients to ophthalmologists to test for retinopathy, after which the specialists will take responsibility for the specific condition but leave basic care to the PCP. He questions whether hepatologists have the bandwidth to play a similar role. Roger notes an earlier discussion (S4 E50.3), in which Naim Alkhouri mentions PCPs' concern that hepatologists will "steal" total care of the MASLD patient. Hannes notes that European systems do not operate this way. Louise comments that in the UK, 95% of all scans require no new treatment, which means that a nurse-based system can pinpoint challenges and spread workload among appropriate specialties. To her, this makes pathway development "absolutely key."
Hannes asks Roger for historical context on this issue. Roger suggests that acceptance of the importance of MASLD feels to him similar to the final acceptance of the cholesterol hypothesis in the 1980s, but in terms of drug development and treatments, more like hypertension in the 1950s when there were multiple modes of action available, none of which were efficacious for most patients as monotherapies. He also notes that we do not know which care paradigms will hold (his example: oncology, with its induction vs. maintenance drug choices and cycles).
He notes the group is looking at many issues, most of which focus on prediction modeling and treatment response. One project he describes focuses on providing a prediction model that is meaningfully superior to FIB-4 and is based on primary care practices, not clinical trial groups. He also describes work on "emulated target trials," in which the researcher can compare historical data to current clinical trials using advanced statistical techniques. The goal here is to create comparisons on a range of questions, including intention to treat and protocol effects. Finally, Hannes mentions beginning work on treatment response markers, where his team is in the early stages, partly because there are no approved drugs to support these analyses in a larger population.
In 2024, Hannes sees potential "game changers" as coming not only from drug development (and hopefully approvals), but also work on diagnostic markers and new kinds of multi-center, multi-region collaborations that will create larger, richer and more diverse data sets than researchers have today.
Surfing the MASH Tsunami continues its 2023 wrap-up conversations with HistoIndex Chief Scientific Officer Dean Tai, along with co-hosts Jörn Schattenberg and Roger Green. The conversation focuses on growth in the use of AI in Steatotic Liver Disease and some of the insights the profession is developing as a result.
The conversation starts with Dean Tai and Jörn Schattenberg discussing the many promising advances in artificial intelligence over the past year. The two leaders agree both that the advances are providing exceptional new insights already, and will provide even greater insight when we can link AI to outcomes. Roger Green also notes how important it is that we improve the insights we develop from biopsy and, at the same time, the quality of non-invasive tests and suggests that AI has the ability to help on both issues. Finally, from the patient perspective, Louise Campbell suggests that anything that reduces the number of patients we biopsy or the number of biopsies per patient is a significant advance.
To be more specific, Dean points out that some of the newer clinical trials are yielding decreases of 30-70% in liver fat density, along with significant decreases in liver volume. Since these measures reduce faster than fibrosis, AI is now giving us the ability to learn more about the process of fibrosis reduction in the aftermath of density and volume declines. Jörn notes that one important issue here involves differences in how pathologists and AI read changes in fibrosis. Specifically, we sometimes overread fibrosis levels in the presence of fast liver fat reductions. He also notes that we can combine these findings with direct fibrosis measures to learn even more and faster. Louise anticipates that this will provide additional benefits if we can fit patient quality-of-life metrics with this data to pinpoint when in the disease treatment process patients begin actually to feel better.
Dean goes on to a second point. AI allows researchers to explore reductions in different regions of the liver in terms of how different regions relate to outcomes. He also points out that in Steatotic Liver Diseases, we see that fibrosis continues in parallel with fibrolysis, which researchers now need to consider in the context of overall disease. Roger mentions two items: that Dean has said in private conversation that in AI-based studies, placebo response usually occurs in ~1/3 of patients and, separately, that bariatric studies suggest that one level of regression might require five years. Dean responds by saying that AI allows us to determine when underlying disease is resolving even if the pathologist considers the patient as presenting with regressive disease.
Roger asks whether AI can be used to assure patients how thoroughly we have studied these drugs and how much we have learned and, separately, to demonstrate more value to payers than we believe using "naked eye" data. Dean suggests the keys will be to simplify the data we present and also to generate a joint statement from the entire community on these issues.
Looking at 2024, Dean anticipates more and richer data than we have. He also cautions that we should shift from biopsy to NITs in clinical trials before we have developed deeper knowledge on how the liver works and what NITs must capture. In this process, he envisions 2024 as a "proof-of-concept" year before we can move to totally non-invasive monitoring in 2025 or 2026. Jörn, who had dropped off the conversation for a few moments, suggested that AI will improve clinical practice over time as well.
In closing, Dean states his concern for 2024 is that we shift too quickly from biopsy to NITs. Louise comments that we cannot discredit biopsy (at least, not yet) and that providers can explain to patients why it is necessary.
Surfing the MASH Tsunami continues its 2023 wrap-up conversations with hepatology researcher and key opinion leader Naim Alkhouri of the Arizona Liver Health Institute, along with co-hosts Louise Campbell and Roger Green. The conversation focuses on viewing the year's major events in drug development, non-invasive tests (NITs) and clinical care pathways.
This conversation starts with Roger asking Naim his reaction to 2023. Naim starts by mentioning his disappointment that OCA did not get approved but shares his vision that the data presentation did not support approval and his hope and belief that resmetirom will fare better. From there, he shifts quickly to discuss being "a little bit disappointed" at the implementation of the AACE and AGA guidelines. In practical terms, he has not seen a single referral from primary care practices (PCP) for elevated FIB-4. He notes that this will require better education of PCPs, but also expresses concern that the guidelines might not be practical for them. In the effort "not to miss a single patient," he believes, authors have created a system with too many patients screened, found negative, and sent back to the PCP. Instead, he suggests, guidelines should have a more realistic goal (reducing unidentified patients from 95% to 80%) and rely on higher FIB-4 cutoffs until PCPs have integrated the concept of MASH screening into their practices. Wrapping up his view of 2023, he describes it as a "good year," although unfortunately one in which drug approval and increased pathway use did not occur.
Roger suggests that the same phenomenon -- worrying more about making things perfect than making them implementable -- applied to the original rollout of the new nomenclature as well as pathways, and goes on to discuss what he sees as the behavioral psychology implications of the pathway guidelines. Naim responds with two suggestions: raise the minimum PIB-4 score at which patients are referred to 2.67 and, in the US, reflex to an ELF test before sending patients to specialists. Louise notes that ELF is not as readily available in the UK as Americans might assume. Roger adds that it might be of value to educate PCPs on the value of FIB-4 as predictive of MACE and other forms of mortality.
Roger asks Naim to describe the "biggest wins" of 2023. Naim starts by citing specific advances in NITs, specifically mentioning NIS-2+ and MASEF (discussed in S4 E39). In terms of medications, he discussed the double- and triple-incretin agonists and their ability to support patients in defatting their livers and notes that, of course, resmetirom's positive Phase 3 results are the biggest story. His third item is the expansion of multi-specialty meetings that educate other specialties on SLD, why it matters, and what roles the other specialties can play in diagnosing and managing MASH patients.
Roger's next question is about disappointments. Naim wishes FDA had moved further and faster in alternate drug approval pathways and metrics, but sees progress in terms of their openness to exploring NITs and, more exciting, their recently stated willingness to grant full approvals in cirrhosis based on histology. Roger asks how AI fits into the emerging picture. Naim states that AI analyses can teach a great deal about the disease, but is not practical for patient treatment.
The last question: his most optimistic picture for 2024 starts with resmetirom approval, goes on to mention several exciting potential drug development results and then discusses creating MASL Centers of Excellence relying on robust NITs for diagnosis and management.
Surfing the MASH Tsunami continues its 2023 wrap-up conversations with patients and patient advocates Mike Betel of the Fatty Liver Alliance (Canada) and Tony Villiotti of NASH kNOWledge (Pittsburgh, PA), along with co-hosts Jörn Schattenberg and Roger Green. The conversation focuses on viewing the year's major events and upcoming priorities from a patient advocate's point of view.
The conversation starts by looking at the roles that patient advocates in different countries have played in the global mix. The conversation starts by focusing on highlights and not-so-highlights of the year, with the first group including the return of face-to-face conferences with active patient involvement and education, the second group including the complete response letter for obeticholic acid and the new nomenclature seen as generally positive but somewhere in the middle.
The conversation's first deep dive comes around the new nomenclature. Mike notes that this was an important initiative for every stakeholder in the MASLD/NAFLD community during the year. Tony describes himself as originally having been opposed because of all the re-work it will require for his organization and also because at a 1:1 level, it becomes hard to envision a physician explaining this disease to patients without raising the concept of "fat." They start by discussing liquid tests, but Mike then shifts to VCTE and the idea that Canadian patients wait six months for VCTE, which is not tenable in the long-run. Mike discusses having gone to the Canadian parliament this past spring and that he learned how little members know about MASLD. He sees increased meetings and conversations, particularly with patients telling their own stories, as critical to building government support.
In response to a question from Roger, both Tony and Mike consider the new nomenclature background noise that will not meaningfully affect how patients and their providers communicate. Jörn notes that in German, he cannot discuss metabolic disease or steatosis because they will mean nothing to the patient, so he uses the term "fat liver," which is the literal German translation.
The conversation shifts to the concept of "stigma", with Jórn starting by noting that the phrase "fat liver" has little stigma. Tony and Jörn agree that framing the issue properly can overcome any perceived stigma on the part of patients. The group agrees that it will take time for stakeholders to adopt the nomenclature, but, as Mike says, "it's here" and everyone will need to get used to it.
In response to a question from Roger, both Mike and Tony highlight increased use of and access to non-invasive testing (NITs) as a primary advocate goal for 2024. They also discuss gaining access to VCTE on a timely basis.
Roger asks what listeners should consider about working more effectively with patient advocate groups. Mike starts by asking that manufacturers and sponsors bring patients into the clinical trial design process far earlier. He also notes that patient advocate groups need financial support from all sources including manufacturers, to support education. Tony mentions the importance of working with children, going into schools to educate children, and, through them, to reach the parents.
Advocates' hopes for 2024 start with the idea of resmetirom being approved. Mike looks to learn more about what primary care physicians in Canada are doing now and how he can motivate them to do more. Mike and Roger discuss strategies for working with industry. Tony mentions the importance of motivating patients to seek their own care. The last comments are around the availability of multi-lingual materials in the two countries.
Surfing the MASH Tsunami kicks off its 2023 wrap-up conversations with Jeff Lazarus, the 2023 winner of the Distinguished Scientific Achievement Award from the American Liver Foundation. He discusses three core MASLD-related opportunities for which he played a key role in 2023: the Research in Action initiative, the new MASLD nomenclature process and the Healthy Livers, Healthy Lives coalition.
Most of this discussion focuses on Jeff's work leading the Research in Action coalition. As Jeff notes, this was the first time the MASLD "field has set its own agenda." Absent governmental or not-for-profit agencies driving the discussion, a group that has grown to over 400 collaborators published its own action agenda in AASLD and EASL publications. Jeff discusses the process through which he built this consensus, focusing on domains identified in earlier meetings: (i) treatment and care; (ii) models of care; (lll) increased awareness; and (iv) leadership. Jeff feels the legitimacy of this activity comes from "casting the net wide" with a series of Wilton Park meetings and from demonstrating how far MASLD lagged behind other non-communicable diseases in terms of goal development, structured support and public presence. Another key element in the initiative's success was a side event at the World Health Assembly led by the four major hepatology organizations, including not only AASLD and EASL but also APASL, and ALEH. Efforts to create parity with other non-communicable diseases will result in increased funding and "massive" increases in awareness.
Today, the other NCDs mention other related metabolic diseases but not MASLD or MASH. Another example of the lack of urgency around MASLD: NIH just put out a call for funding for HIV, which Jeff notes might not be as high a priority in 2024 as MASLD.
At this point, Jörn Schattenberg joins the conversation to congratulate Jeff on his recognition and award and also to discuss how important it is to the entire community that Jeff plays the role he does. In response, Jeff comments that one benefit of the Award is that it ratifies the importance of the kinds of consensus building and application of public health initiatives in MASLD space.
From here, Jeff and Jörn step further forward to discuss the importance of funding prevention and education programs, done by governments in the EU and perhaps public or private players in the US. Jörn discusses the multidisciplinary nature of the Barcelona meeting they co-chair and how it provides outreach beyond hepatology. Jeff continues the thought to discuss the importance of social determinants of health (for example, food insecurity) in a world where healthy foods cost far more than more common alternatives (basmati rice costs 3x basic white rice).
Roger asks how the new nomenclature is proceeding. Jeff says it is doing quite well in that there is significant global buy-in. Major centers around the world are adopting the new nomenclature for their meetings and clinics, but, Jeff notes, it is difficult for physicians to explain the disease to patients without using the words "fat" or "fatty."
As the conversation winds up, Jeff notes the importance of bringing primary care to the education and outreach processes and the goal of doubling the number of patients screened over the next four years. The conversation closes on this note: much that must be done, but confidence that the energy to achieve these big goals is coalescing properly.
This Vault conversation stems from the wrap-up to TLM2022. In the episode, the panel (Jörn Schattenberg, William Alazawi, Naim Alkhouri, Laurent Castera, Ken Cusi, Wayne Eskridge and Roger Green) addresses several topics from the program. This one focuses largely on NITs.
This conversation focuses on several papers of interest to Laurent. The first is a prospective screening study on patients with diabetes seen in either primary care or a diabetes clinic in the US. Using NITs to screen for NASH and MRE to screen for advanced disease, they identified 65% with NAFLD, 14% with advanced fibrosis and 5% with cirrhosis. When 164 of these patients moved into biopsy, they identified 61% with NAFLD, 30% advanced NASH and 9% cirrhosis. Laurent contrasts these results to a similar study conducted in a French diabetes clinic-treated cohort with transaminase greater than 20 in women and 30 in men. This yielded 58% NASH, 38% advanced fibrosis and 10% cirrhosis.
The panelists then explore the implications of both studies in terms of how screening should be conducted today. Laurent estimates that we might miss ~25% of advanced patients using current VCTE cutoffs without additional parameters. He also notes that neither duration of diabetes nor A1c levels were predictive. The group concludes that, as Ken puts it, studies like these push the needle toward action in both primary care and diabetes settings.
This conversation between Scott Friedman, Laurent Castera, Louise Campbell and Roger Green covers a pivotal session on the new MASLD nomenclature, plus what the panelists found exciting and important about the developing class of triple agonists, at TLM 2023.
This conversation starts with Roger stepping gently into the topic of the new MASLD nomenclature by discussing a Saturday morning session chaired by Maru Rinella and Meena Bansal. The session took a broad, fairly detailed view of progress in knowledge and implementation of this nomenclature. Roger's point: two of the three obvious potential downsides to the new nomenclature are now rendered resolved. First, George Makar of FDA stated that the agency now uses the terms “MASH” and “NASH” or “MASLD” and “NAFLD” interchangeably, which means that the nomenclature will cause no delays or rework around drug and device clinical trials. Second, Quentin Anstee and Arun Sanyal reported from the LITMUS and NIMBLE databases that the patient overlap when mapping against the two definitions was 95-98%, which means there should be no dispute around the impact on how we define patient populations. In this regard, Roger notes that Gregory Gores, editor-in-chief of Hepatology, said the journal believes this issue is over and will not accept more publications on the subject.
The third item is the perceived stigma around the word “fat.” Roger quotes NASH kNOWledge founder and patient advocate Tony Villiotti, who points out that while we may describe a specific medical event as a myocardial infarction, the doctor still tells the patient "You had a heart attack." Similarly, the concept of “fat on the liver” will be essentially to explain what is going on to the patient, whatever the nomenclature says. This leads Laurent to discuss the paper on stigma presented at the conference which suggests that "fatty liver" is far less stigmatizing in general than "obesity" or "diabetes," and some specific nuances of the paper. When he is done, Scott and Roger comment on vastly different moments in history and regions in the world where obesity was actually considered a sign of something positive.
This entire discussion leads Scott to remember a presentation on Eli Lilly's triple agonist retatrutide and the remarkable impact this class of drugs is likely to have on how we manage obesity, diabetes and liver disease. Roger notes that Altimmune and Merck/Hanmi have similar agents in development. He goes on to note that these drugs demonstrate levels of weight loss found with bariatric surgery and asks Laurent and Scott whether they believe the drugs will have impact similar to surgery. Both say it is too early to tell. Louise follows this by mentioning a study showing that allied health professionals are proficient at motivating patients to lose weight, maintain that loss, and do so in healthy ways.
Roger's wrap-up question asks what will be different at TLM2024 next year in San Diego. You’ll have to listen to hear the answers.
This conversation between Scott Friedman, Laurent Castera, Louise Campbell and Roger Green covers what the panelists found exciting, important or striking about liver science, VCTE, regulatory approvals using NITs or AI, and other issues at TLM 2023.
It starts with Roger sharing his belief that regulators are likely to approve NITs only if a small battery of tests (or ideally, a single test) prove valuable in assessing all agents, or at least all agents, for a stage of disease or segment of the market. Scott notes his frustration that biopsy is an expensive and poorly-graded measure and hopes that FDA will move past semi-qualitative biopsy.
Roger asks Scott what we learned about basic science in the meeting. Scott discusses advances in single-cell technologies as pivotal in helping us understand underlying disease better, and goes on to mention several presentations on senescent cells that provided insight but, he felt, little for basic drug development.
Roger then asks Louise what in the meeting she found most interesting. She points to two posters regarding VCTE. The first looks at liver stiffness and controlled attenuation parameter, or CAP in patients after transplantation. Louise describes this as the first time she has seen CAP used as an independent predictor. She mentions a second poster on methotrexate using VCTE as having similar promise to expand VCTE as a research tool.
Louise then goes on to discuss a poster addressing the evolving impact of allied providers in hepatology. In this poster, the authors projected a roughly 1/3 growth in hepatology patients by 2023 requiring treatment, coupled with a roughly 1/3 decline in the number of hepatologists available to treat them. Allied providers in hepatology showed a similar trend. To Louise, this signaled clearly that all countries need to boost the number of allied providers if these patients are to receive the care they will need. As the conversation winds down, Louise and Roger discuss the high level of patient presence and energy suffusing the entire event.
This conversation between Scott Friedman, Laurent Castera, Louise Campbell and Roger Green covers what the panelists found exciting, important or striking about the presentations covering NITs, artificial intelligence and bariatric surgery at TLM2023.
The conversation starts with Roger discussing a presentation in which Stephen Harrison shared HistoIndex data from the MAESTRO-NASH trial for resmetirom. HistoIndex’s proprietary methods produced results suggesting 34% improvement in the placebo group vs. 54% in the treatment group. More interesting, Dean Tai from HistoIndex suggested to Roger in a private conversation that this 1/3 placebo success rate holds fairly common across trials using these methods. Given that bariatric surgery studies suggest a five-year gap from successful surgery to fibrosis regression, the one-year standard requested by FDA for conditional approval might lead us to understate drug efficacy for resmetirom and later New Drug Applications submitted under these criteria.
Laurent discusses a study from Phillipe Mathurin’s group in France that demonstrates among bariatric surgery patients, MASH resolution and fibrosis regression lead to improved outcomes. His point: it is important that this study confirms the idea that MASH resolution and fibrosis regression do, in fact, lead to fewer Major Adverse Liver Outcomes, or MALO.
The conversation shifts to NITs and the value of biomarkers in proving that a drug is working. Laurent notes that no single market is sufficiently reliable and that we will need a cluster of tests to evaluate any given drug. As an example, he cites the impact of BMI on liver stiffness as a confounder that does not exist in other tests like ELF. Scott asks about HepQuant; Laurent has limited experience but finds the idea conceptually appealing. Scott notes that the slow rollout and low budget might be responsible for the lack of market and academic interest.
Laurent focuses on a specific poster looking at a database of 16,000 patients over two years. The study shows that an increase in liver stiffness, AGILE-3 or AGILE-4 score all correlate with MALOs. What the study doesn’t address, and Laurent points up will be key to learn, is whether declines in these measures correlate with improved outcomes among declining patients.
This conversation between Scott Friedman, Laurent Castera, Louise Campbell and Roger Green covers what the panelists found exciting, important or striking about the presentations of clinical trial results at TLM2023.
Instead of focusing immediately on MASH drugs, Scott suggested we should not overlook the idea that elafibranor is preparing to come to market in the US as a novel medication for PBC with good efficacy and safety from patients who do not respond well to ursodiol or obeticholic acid. I note that elafibranor is only one of two PPARs speeding toward market in PBC with exciting data given what we all heard in the late-breaker presentation on seladelpar. Scott also mentions to integrin antagonist from Pliant in PSC, a disease with no available solutions today. Laurent agrees with Scott that the rare disease drug advances were more exciting than the advances in more common liver diseases.
I bring up papers addressing the value of FGF-21 and FGF-19 agents in cirrhosis, which showed some promise for compensated cirrhotic patients. Scott politely disagrees, feeling that while these agents might hold disease steady, they do not address the challenges and mechanisms necessary to meaningfully regress disease. We agree there is a benefit to any agent that slows or reverses the course of disease even slightly in that this buys the patient more time to be treated with more exciting medications still in the pipeline.
Scott notes that for Hepatitis C, a far simpler disease it took 25 years from discovery to cure on a path of incremental process. Scott notes that drug development successes are keeping investors interested, which is encouraging in a challenging environment for investment.
Laurent returns to the issue of cirrhosis, noting that there are multiple challenges and concomitant bad behaviors like alcohol consumption. He points out that where good studies exist, these are short studies with small samples. Scott points out that MASH is less like hepatitis and more like inflammatory diseases like IBD, where causes of underlying disease are difficult to determine and there is no single pathway in drug development. He buttresses this by noting that in clinical trials, resmetirom provided benefit to only 25% of patients.
This conversation between Scott Friedman, Laurent Castera, Louise Campbell and Roger Green covers the four panelists’ general impressions of TLM2023, both the good and bad of it.
Scott starts with a simple statement: “It was good to be at an AASLD that felt like an AASLD. Specifically, Scott is talking about the energy and excitement associated with the meeting. He also approves of Boston as a meeting location.
Scott’s meeting worst was the meeting app. The group elaborates on why they all agree.
Laurent Castera agrees with Scott: bad app; excellent meeting with a great deal of colleague interaction.
As a virtual attendee, Louise felt her own unique pain with the app. In addition, only 20% of sessions were live, and many were Zoom, which meant ‘Zoom in the US.’ She describes this as the most disappointing meeting experience, and she notes that some people paid $1,200 for it.
I make two other points: the patient tracks were broad in coverage and highly well-attended, and Saturday night’s Diwali celebration. Scott, Laurent and I agree that the meeting was genuinely crowded and hot…but worthwhile.
My final comment: tremendous excitement and anticipation about March 14, resmetirom’s PDUFA date at the FDA.
Hepatology researchers and key opinion leaders Profs. Laurent Castera and Scott Friedman join Louise Campbell and Roger Green in the final element of our review coverage of TLM 2023. This far-ranging conversation moves beyond MASLD/NAFLD and MASH/NASH to consider an array of topics.
The episode starts with Roger asking the other guests for their general impressions of the meeting. Three key insights:
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"Pre-pandemic" levels of interaction and discussion among attendees
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Online meeting app was a "fail", becoming a topic of conversation in its own right while fostering confusion
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In the "frenzy" about the anticipated resmetirom approval and other MASH drugs approaching market, we shouldn't overlook that patients with PBC will soon have two new exciting PPAR agents, elafibranor and seladelpar. As Scott notes, we also learned about promising modes of action for PSC so, overall, a promising meeting for rare cholestatic diseases.
The rest of this discussion covers multiple topics, key among them:
· Impact of FGF-21 and FGF-19 agents on patients with compensated cirrhosis. Roger is optimistic that agents might provide improvement. Scott is more pessimistic because we do not have agents addressing the unique mechanistic challenges in cirrhosis vs. advanced fibrosis. Both agree that agents on the horizon can buy time until curative or regressive medications arrive.
· AI-based analysis. Roger bridges to Stephen Harrison’s presentation of HistoIndex analysis of resmetirom that produces an estimate of 54% efficacy vs. 34% placebo. He comments that given this analysis and that bariatric surgery studies tell us fibrosis regression may take five years, the FDA one-year standard might be so stringent as to be misleading.
· Bariatric surgery. Laurent refers to a presentation from Phillippe Mathurin's group demonstrating that in patients post-bariatric surgery, MASH resolution and fibrosis regression clearly lead to improved outcomes.
· NITs. Laurent discusses a poster from a multi-country 16,000-patient cohort that did not confirm liver stiffness as leading to a decline in MALO over a two-year period but anticipates more robust findings over time.
· VCTE-based analysis. Louise discusses two posters with analyses based on FibroScan. The first, from the Virginia Commonwealth University and the VA, found that liver stiffness correlates with success in liver transplant and that CAP can predict the risk of future MI in these patients. She notes that CAP of 270 served as "its own parameter" in predicting time to mortality.
· Nomenclature. Roger notes that a Saturday morning session resolved the two most pivotal outstanding issues about the effect of nomenclature change on scientific development. FDA signaled that the agency views old and new nomenclature terms as interchangeable. NIMBLE and LITMUS analysis determined that patient mapping is also interchangeable.
· Impact of triple-agents. Presentations at this conference confirm that triple agents addressing GLP-1, glucagon and GIP can have bariatric surgery-level impact on liver fat and reduce the entire disease burden.
Interspersed between these topics are a range of insights on cirrhosis disease models, regulatory slowness in moving on from current conditional efficacy metrics, treater supply vs. patient demand, "stigma", and basic science. This is a high-level view of an information-dense conversation. Listen to learn more and hear all the details.
Fatty Liver Alliance President and Founder Mike Betel, a leading patient advocate for MASLD/MASH patients, joins Roger Green in our continuing review coverage of TLM 2023. Mr. Betel discusses presentations and events he found most valuable to patient advocates. He also discusses the new MASLD nomenclature and Fatty Liver Alliance's upcoming 2nd Annual Primary Care NAFLD & NASH Summit.
The conversation starts with Mike paying the event a profound but slightly backhanded compliment. He comments that interest in some sessions was so strong that organizers did not leave sufficient space for everyone who wanted to attend. As he pointed out, even the "overflow rooms" were overflowing for some sessions! Mike then paid the event a profound complement: the content of the sessions, coupled with his ability to interact with Key Opinion Leaders, made for a meeting that provided him with insight and enthusiasm into where the field is heading.
Mike shifts focus slightly to praise Madrigal Pharmaceuticals for the Public Service Announcement the company premiered at this event. He describes himself as "blown away" by the 2:30 video. Mike notes, and Roger agrees, that virtually everyone he spoke with at the conference who saw the PSA felt the same way. In response to Roger's question, Mike offers that what makes the PSA so special is that it focuses on "a real person and a real community interacting" in ways that portray real-life with humor and, at the same time, commitment. He mentions a couple of specific items he particularly likes and goes on to note that as of the end of conference, the video had already received 500,000 views online.
Mike goes on to discuss one scientific paper he found compelling, a presentation by Prof. Arun Sanyal about the Eli Lilly incretin triple-agonist retatrutide. He cites Arun's comment that in over 90% of the obese patients in this study, the drug reduced liver fat so much that patients' fat levels were defined as "normal." Roger goes on to note that there are three triple-agonists in development, the other two being Altimmune's pemvidutide and Merck/Hanmi's efinopegdutide.
Shifting focus, Mike congratulates Dr. Jeff Lazarus on being recognized with the Distinguished Scientific Award from the American Liver Foundation. jeff's work over his career has spanned major public health efforts in HIV, Hepatitis C, COVID-19 and Fatty Liver diseases, but his most recent effort was spearheading the Delphi process around the nomenclature change. Roger commends the work that Jeff, Ken Cusi and a few others have made in reaching across specialties and countries to foster and promote clinical care pathways. Mike commends a presentation by Jeff and Mazen Noureddin talking about "a united voice for liver health."
Next, the conversation shifts to discuss the new nomenclature, which received significant attention at TLM 2023. Mike comments that while nomenclature is moving ahead, widespread change will hinge on endorsements from regulators, professional organizations and the pharmaceutical industry. Roger notes two specific steps forward: a comment from George Makar of FDA that the agency sees the terms of interchangeability and reports from Profs. Sanyal and Quentin Anstee that the old and new definitions map identically for 95-98% of patients.
The last part of the discussion focuses on Fatty Liver Alliance's upcoming primary care event. Mike discusses some highlights of the conference and tells listeners how to find it. The podcast ends with a call to action for community-wide engagement in liver health, underscoring the necessity for collaborative efforts to broaden the understanding of liver disease, enhance patient care, and adapt to the evolving medical landscape.
Dr. Tim Jobson of Predictive Health Intelligence joins Roger Green in our continuing review coverage of TLM 2023. Dr. Jobson discusses the studies he presented at the meeting and other work related to population-level screening for metabolic diseases, the importance of providing better care in areas with lower socio-economic status residents and the global value of population health management.
The conversation starts with Tim discussing the major impact that new medicines like resmetirom and new indications for GLP-1s will have on the entire treatment framework for MASLD and MASH, starting with increased interest in screening coming from physicians who will have medications they can use to treat patients. Roger identifies the ability to predict which patients will proceed from MASLD to MASH as a major area for improvement, which serves as a segue to Tim to discuss PHI's work.
PHI presented two posters at TLM2023, mostly focusing on deploying PHI's medical record-based case finding approach to identify specific patients badly in need of care but not receiving it. This is particularly crucial in what Tim describes as "areas of deprivation," with residents of lower socio-economic status. One poster addressed identification of untreated patients with Hepatitis B. The other focused on liver disease in these areas: similar rates of disease but far higher rates of advanced disease.
Tim's is particularly excited about population-level risk stratification and the ability to identify a "five-fold" increase in the people we can target early in adulthood based on their propensity to develop non-communicable disease later in life. This study will target 7% of the population, which he expects will make the program economically viable. Tim reports he has seen tremendous interest in this idea at the meeting, strikingly among US physicians, allied professionals and payers.
The conversation shifts from Tim's work to other issues in the meeting he found fascinating. He was powerfully struck by some of the data and drugs becoming available in Primary Biliary Cholangitis (PBC) and findings about modes of action in Primary Sclerosing Cholangitis (PSC), two rarer diseases vitally in need of better therapies.
Tim also asks where AI will fit into the emerging care paradigms. In this regard, one of his concerns regards the intrinsic biases in existing datasets when we try to predict which patients have more urgent need for a liver transplant among those on the list. Tim and Roger return to the issue of biases in the current dataset, and agree the biases are probably too "hard-wired" to eliminate, which means researchers will need to find ways to adapt...and, Tim believes, they will do so.
Looking at another issue that interested Tim, the discussion shifts to asking what the meeting is telling us about Hepatitis B and Hepatitis C. Tim notes that we are unlikely to meet the ambitious elimination goals we have set. Doing better will involve improved patient identification and motivation, which has two tiers of challenge. In developing countries, the data and data structures necessary to target patients simply do not exist. Even when they do exist, as in the UK, the system reaches only half-to-two-thirds of patients with clear signs of serious disease.
The right strategy for the solution is to pilot in a narrow swath of population, then go broader. As the conversation ends, Tim notes that the technology is here or will be shortly to achieve this goal.
Dr. Zobair Younossi joins Roger Green to kick off our review coverage of TLM 2023. Dr. Younossi discusses the studies he presented at the meeting and other work related to patient quality-of-life, the economics of screening and treatment, and how stigma affects patients and providers.
The conversation starts with Zobair listing the topics on which he and his group will present data at the TLM2023 meeting. The first of these is an oral presentation regarding health disparities in adolescents. The thrust of this work is that food insecurity is leading to dramatic, increasing rates of MASLD and MASH among adolescents. Food insecurity, which correlates with lower incomes and living in "food deserts" -- primarily urban areas where stores sell ultra-processed foods at high prices -- emerges from the NHANES database as a correlation and likely cause of MASLD and even MASH with fibrosis in these younger patients.
Zobair cites alarming statistics about the underestimated prevalence of liver diseases in children and teens. Standard estimates put MASLD in children at 10%, but Zobair believes that number to be closer to 18%, with adolescents as high as 24% and the adult US population at 38%! In parallel, there has been a striking increase in liver disease among type 2 diabetics, which was previously estimated at 55%, but he now estimates at 68%! He notes that "food deserts" also tend to be "activity deserts" without facilities that support a healthy lifestyle.
Roger notes that an increase in patients with Type 2 diabetes and MASH will have significant economic implications: they are more likely to develop cardiovascular disease and obesigenic cancers before they progress to cirrhosis. Also, they are more likely to go from advanced fibrosis to cirrhosis than people with MASH and no diabetes. These social and economic realities emphasize the need for cost-effective screening strategies similar to those recommended by professional societies. Zobair mentions another paper he is presenting at TLM that demonstrates cost-effectiveness for screening in all intermediate-risk patients even before MASH drugs come to market.
From here, the conversation focuses on the factors that make MASLD and MASH so costly. Zobair focuses on fatigue, which affects 30-40% of MASLD patients. Many patients consider fatigue something they live with, not an effect of disease, but MASLD can lead to "brain fog," or cognitive impairment.
Zobair and Roger go on to explore the issue of stigma in the context of conference presentations and Zobair's own work. After noting that stigma was a significant reason for the recent nomenclature change, Zobair reports that it seems less of an issue for patients (8%) than providers, where the number is higher. Roger notes his experiences in marketing research, where providers frequently blamed patients for their disease and expressed frustration or even contempt that patients could not take better care of themselves. Zobair notes that this translates to patients, who express more significant frustration and sadness about being blamed for the disease than simple name-related stigma. Zobair makes two more points on stigma: (i) patients who feel stigmatized have lower quality-of-life scores, and (ii) to patients, obesity and Type 2 diabetes are far more stigmatizing than "fatty liver disease."
The final portion of this conversation focuses on cultural differences. Zobair notes that the stigma associated with obesity and MASH is a Western-world phenomenon and a relatively recent one. In much of the world, obesity can appear as a sign of prosperity because the obese person has enough wealth to buy large quantities of food. They conclude that understanding these nuances is crucial for improving patient-provider communication and addressing factors beyond individual control, such as social determinants and health disparities, which heavily influence health outcomes.
Last week's posting consisted of 1:1 interviews with four KOL from different spheres, each talking with Roger Green about what they are looking forward to seeing at this week's The Liver Meeting 2023. This week, two of those KOLs, co-host Jörn Schattenberg and hepatology KOL Naim Alkhouri, join Roger and co-host Louise Campbell, FRCP, in a free-wheeling review of key abstracts that will be presented at TLM2023.
The discussion begins with Jörn spotlighting the first item in the abstract book, a presentation titled MASH Resolution Without Fibrosis Worsening After Bariatric Surgery Improves Long-Term Survival. Jörn spotlights this study for demonstrating survival benefits, a significant benchmark for drug approval processes. This study of bariatric patients with concomitant MASH and fibrosis reveals that MASH resolution often comes before fibrosis regression. This suggests that MASH resolution itself might predict improved long-term outcomes, contrasting with earlier beliefs that only linked fibrosis regression to positive prognoses. Louise comments that reducing inflammation should logically lead to fibrosis regression, comparing it to the treatment of hepatitis C. Naim agrees, emphasizing the liver's remarkable ability to heal if the initial injury stops, such as with alcohol cessation or hepatitis treatment. However, he points out challenges in clinical definitions and trial inclusions based on the current focus on MASH histology.
The conversation shifts as Naim shares his excitement that both the ENLIVEN trial with FGF-21 agent pegozafermin and the ALPINE-4 trial with FGF-19 agent aldafermin demonstrate the potential for these agents to reduce fibrosis one level (and occasionally even two!) in patients with cirrhosis. The group agrees that treating cirrhosis is the most urgent challenge facing MASLD hepatology today because patients are close to decompensation and antifibrotic pharmacotherapy does not exist. This leads Roger to ask whether the presence of these agents will drive more aggressive screening for cirrhosis patients and for the group to list the benefits early screening will offer.
Louise shares two papers she intends to follow, both of which focus on gender disparities in liver health. She reminds the group of Roberta Forlano's research (shared in S4 E44) and comments during that discussion that women in liver failure experience higher rates of death that man -- they do not fare as well on liver transplant lists and exhibit higher rates associated with hepatic renal syndrome. The group concurs that this disparity needs more attention and fits into a broader issue of inequality in medical treatment based on gender and other demographic factors.
Roger shares two posters on lanifibranor with an eye toward how payers are likely to assess agents when they come to market. As the group discussed in earlier episodes, there are significant challenges identifying which patients are likely to succeed prospectively on a MASH drug and another on determining in a reasonable timeframe whether the medication is working. Of the two lanifibranor posters, one suggests that changes in adiponectin levels can predict level of therapeutic success, while the other shows that presence of a mutated PNPLA3 gene has minimal or no impact on the likelihood of therapeutic success.
The group discusses a few other papers and concepts. One paper of note came from the NAIT-NIT consortium and suggests that biopsy can lead to an overestimation of liver fat levels compared to MRI-PDFF. Naim and Jörn comment on behavioral or attitudinal constructs from hepatologists that might lead to this result.
Finally, the group comments on the importance of late-breakers as a vital conduit or cutting edge research and each member notes one other paper or session at the meeting they find intriguing.
STAY SAFE AND SURF ON!
This week on Surfing NASH, host Roger Green embarks on a series of one on one interviews with KOLs and patient advocates to talk about the Liver Meeting 2023 (held in Boston from November 10 - 14) and much more. In this conversation, friend of the podcast, Naim Alkhouri, joins to discuss this highly anticipated event as well as offer a glimpse into his current work and research interests.
The Liver Meeting is known for its exceptional educational content and amazing presenters. This year will be no exception and, if you can't make it to Boston, the state-of-the-art lectures will also be available online. If you have questions or comments stemming from this conversation, the Liver Meeting, or our interview series in general, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
This week on Surfing NASH, host Roger Green embarks on a series of one on one interviews with KOLs and patient advocates to talk about the Liver Meeting 2023 (held in Boston from November 10 - 14) and much more. In this conversation, Key Opinion Leader, Scott Isaacs, joins to discuss this highly anticipated event as well as offer a glimpse into his current work and research interests.
The Liver Meeting is known for its exceptional educational content and amazing presenters. This year will be no exception and, if you can't make it to Boston, the state-of-the-art lectures will also be available online. If you have questions or comments stemming from this conversation, the Liver Meeting, or our interview series in general, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
This week on Surfing NASH, host Roger Green embarks on a series of one on one interviews with KOLs and patient advocates to talk about anticipations around the Liver Meeting 2023 (held in Boston from November 10 - 14) and much more. In this session, President of the Fatty Liver Alliance, Michael Betel, joins to discuss this highly anticipated event, plus some additional key ideas around patient advocacy.
The Liver Meeting is known for its exceptional educational content and amazing presenters. This year will be no exception and, if you can't make it to Boston, the state-of-the-art lectures will also be available online. If you have questions or comments stemming from this conversation, the Liver Meeting, or our interview series in general, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
This week on Surfing NASH, host Roger Green embarks on a series of one on one interviews with KOLs and patient advocates to talk about the Liver Meeting 2023 (held in Boston from November 10 - 14) and much more. In this first conversation, Jörn Schattenberg joins to discuss this highly anticipated event as well as offer a glimpse into his current work and research interests.
The Liver Meeting is known for its exceptional educational content and amazing presenters. This year will be no exception and, if you can't make it to Boston, the state-of-the-art lectures will also be available online. If you have questions or comments stemming from this conversation, the Liver Meeting, or our interview series in general, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
In continuation of the Surfing NASH interview series, Roger Green talks to Professor Oren Shibolet, Head of Gastroenterology and Hepatology at the Tel Aviv Medical Center. This is a powerful discussion which touches on the Hamas invasion on October 7 and its aftermath on the Israeli people and the practice of medicine today.
This conversation From the Vault reprises our earlier interview from June with Tetiana Deshko, Director of Programs for the Alliance for Public Health in Ukraine. Dr. Deshko shared her own experience with the challenges of providing health for patients in the midst of an invasion, particularly in occupied and battleground areas.
Think of this From the Vault episode as a dramatically expanded weekly business report, in which Roger discusses the situation in Ukraine. Dr. Deshko's description is powerful and provokes emotions that words cannot describe. You can support her vital public health work by making donation to the Alliance for Public Health, one of the largest non-governmental organizations in Ukraine, (click this link to donate and read more about their important work).
If you have any question or interests around the event or Ms. Deshko's experiences in Ukraine, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On! Перемагаймо разом!
In continuation of the Surfing NASH interview series, Roger Green talks to Professor Oren Shibolet, Head of Gastroenterology and Hepatology at the Tel Aviv Medical Center. This is a powerful discussion which touches on the Hamas invasion on October 7 and its aftermath on the Israeli people and the practice of medicine today.
In this conversation, Oren discusses ways that the Hamas invasion and slaughter have affected the collective perspective of Israelis. At the end, he also shares concerns about the long-term impact of the invasion and likely war to come on the practice of hepatology at his center, which has been until now a leading clinical trial site. This description cannot begin to touch on the gravity of this conversation, so surf on for the full account.
If you have questions or comments stemming from this episode, or the interview series in general, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
In continuation of the Surfing NASH interview series, Roger Green talks to Professor Oren Shibolet, Head of Gastroenterology and Hepatology at the Tel Aviv Medical Center. This is a powerful discussion which touches on the Hamas invasion on October 7 and its aftermath on the Israeli people and the practice of medicine today. In this conversation, Oren discusses how the events of October 7 have affected the Israeli medical system, focusing largely on the practice of hepatology. Along the way, you will get a flavor of what it is like to live in a place where air raid sirens ring 5-6 times per day and there are strict, life-saving protocols about what to do when you hear the sirens. This description cannot begin to touch on the gravity of this conversation, so surf on for the full account.
If you have questions or comments stemming from this episode, or the interview series in general, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
In continuation of the Surfing NASH interview series, this week Roger Green talks to Professor Oren Shibolet, Head of Gastroenterology and Hepatology at the Tel Aviv Medical Center. This is a powerful discussion which touches on the Hamas invasion on October 7 and its aftermath on the Israeli people and the practice of medicine today. This first conversation starts with Professor Shibolet talking about his career history. From there he shifts to discuss his experiences of October 7, the devastating day of the Hamas terrorist attack.
If you have questions or comments stemming from this episode, or the interview series in general, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
In continuation of the Surfing NASH interview series, this week Roger Green talks to Professor Oren Shibolet, Head of Gastroenterology and Hepatology at the Tel Aviv Medical Center. This is a powerful discussion which touches on the Hamas invasion on October 7 and its aftermath on the Israeli people and the practice of medicine today. Surf on to learn more about this current complex issue and more.
If you have questions or comments stemming from this episode, or the interview series in general, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
One of the most important challenges facing Fatty Liver stakeholders involves improving early diagnosis for patients with clinically relevant or advanced fibrosis (F2/3). Today, a significant percentage of patients learn they are living with cirrhosis in the Emergency Department during a decompensating event. Four in ten of these patients in the UK do not leave the hospital. This episode From the Vault reviewed a model that Ian Rowe and Richard Parker developed to determine the most cost-effective strategy for F2/3 diagnosis.
In this conversation, Ian Rowe describes the factors that motivated him and Richard Parker to build a decision model focusing on early NASH diagnosis. He identifies three data points demonstrating how severely NASH stakeholders need a better early diagnosis paradigm and then describes the five diagnostic strategies his model will test. :
- the high percentage of people whose liver disease is picked up for the first time when they present in the ED with decompensating disease or hepatic encephalopathy
- the fact that roughly four in ten of these patients will die during treatment for this initial round of liver disease
- the inefficiencies around diagnostic current methods, whereby practitioners flag abnormal liver enzyme tests and refer to specialists, where it may take months to get a specialist appointment.
- He then describes the five early diagnostic strategies that will be tested and contrasted in this decision curve model.
This week on SurfingNASH, we introduce the audience to new guest, Dr Roberta Forlano, who's been awarded an EASL Juan Rodes PhD Fellowship and has completed a PhD in Translational Hepatology at Imperial college London in 2022. Her current research interest are screening strategies for NAFLD in primary care, automated quantitation of histological features , lifestyle management, CV risk assessment and non-invasive markers in NAFLD. These interests and much more are shared and discussed with Jörn Schattenberg, Louise Campbell and Roger Green in a compelling episode with an overarching theme focusing on screening strategies for gender-based SLD challenges. To offer an example of how immensely productive and busy Roberta and her team have been, they recently presented 6 posters at the recently concluded SLD Summit.
This final conversation covers the other paper discussed in the episoe at large, a literature review looking at how MASH and MASLD might differ in women compared to men. Roberta starts by noting the gap in literature about gender differences in MASH studies, and that women appear represented in most clinical trials. Most of the rest of the conversation involves Roberta and Louise commenting on gender differences and the impact of menopausal status on MASH and MASLD in women. When this finishes, Roger asks Louise and Jörn to describe one thing we discussed that might affect their practices or patterns. He also asks Roberta what she would like listeners to take away from the conversation.
With that as a very brief introduction to a fascinating conversation well-worth a listen, surf on to learn more about Roberta and critical ideas around screening strategies and much more. If you have questions or comments stemming from this episode, or any others for that matter, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
This week on SurfingNASH, we introduce the audience to new guest, Dr Roberta Forlano, who's been awarded an EASL Juan Rodes PhD Fellowship and has completed a PhD in Translational Hepatology at Imperial college London in 2022. Her current research interest are screening strategies for NAFLD in primary care, automated quantitation of histological features , lifestyle management, CV risk assessment and non-invasive markers in NAFLD. These interests and much more are shared and discussed with Jörn Schattenberg, Louise Campbell and Roger Green in a compelling episode with an overarching theme focusing on screening strategies for gender-based SLD challenges. To offer an example of how immensely productive and busy Roberta and her team have been, they recently presented 6 posters at the recently concluded SLD Summit.
This conversation starts with Roger asking Roberta to describe the demographics of the population in the northwest London region where the study of interest was done. Roberta comments on the robust diversity of the population, after which Louise amplifies this point by noting the large number of Arabic and South Asian patients in the study population. She discusses why culturally this might matter and the challenges that those populations might present. From there, we discuss the P-values associated with different diabetes drug therapies and their impact on MASH and simple diagnostic methods. Finally, ideas are shared around challenges which may present to patients which ultimately persuade them not to participate in a study.
With that as a very brief introduction to a fascinating conversation well-worth a listen, surf on to learn more about Roberta and critical ideas around screening strategies and much more. If you have questions or comments stemming from this episode, or any others for that matter, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
This week on SurfingNASH, we introduce the audience to new guest, Dr Roberta Forlano, who's been awarded an EASL Juan Rodes PhD Fellowship and has completed a PhD in Translational Hepatology at Imperial college London in 2022. Her current research interest are screening strategies for NAFLD in primary care, automated quantitation of histological features , lifestyle management, CV risk assessment and non-invasive markers in NAFLD. These interests and much more are shared and discussed with Jörn Schattenberg, Louise Campbell and Roger Green in a compelling episode with an overarching theme focusing on screening strategies for gender-based SLD challenges. To offer an example of how immensely productive and busy Roberta and her team have been, they recently presented 6 posters at the recently concluded SLD Summit.
This conversation starts with your Jörn returning to a key point from Roberta's paper around a 38% false negative rate for FIB-4 screening. Jörn notes that while this feels like a high rate for false negatives, it might not present as much of a diagnostic challenge if treaters repeat the screening every 2 to 3 years. Roberta agrees and notes how remarkably cost effective this screening strategy is. Even in an environment with no approved drugs for MASH, Louise notes that the false negative rate for Enhanced Liver Fibrosis (ELF™) Test was far higher, which Roberta attributed to the test thresholds which were set for severe disease. She suggests that if health is to be used in these situations, the cutoffs need to be far lower. From there, the group goes into several issues of the paper the value of VCTE diagnostics, the common theme that most patients come from a background of lower socioeconomic status and the idea that simple ultrasound produced reasonably reliable results. This last point matters tremendously because primary care clinics throughout the world are more likely to have access to ultrasound than VCTE, and in some countries, ultrasound is the only imaging technique reimbursed by the health care system.
With that as a very brief introduction to a fascinating conversation well-worth a listen, surf on to learn more about Roberta and critical ideas around screening strategies and much more. If you have questions or comments stemming from this episode, or any others for that matter, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
This week on SurfingNASH, we introduce the audience to new guest, Dr Roberta Forlano, who's been awarded an EASL Juan Rodes PhD Fellowship and has completed a PhD in Translational Hepatology at Imperial College London in 2022. Her current research interest are screening strategies for NAFLD in primary care, automated quantitation of histological features , lifestyle management, CV risk assessment and non-invasive markers in NAFLD. These interests and much more are shared and discussed with Jörn Schattenberg, Louise Campbell and Roger Green in a compelling episode with an overarching theme focusing on screening strategies for gender-based SLD challenges. To offer an example of how immensely productive and busy Roberta and her team have been, they recently presented 6 posters at the recently concluded SLD Summit.
This conversation starts with Louise introducing our new guest Surfer and why she felt the various recent papers might be so important for our audience. For Louise, the common thread in much of Roberta's work, and certainly the two papers we discuss in this episode, is the focus on at-risk populations, patients with Type-2 diabetes in primary research, and postmenopausal women in literature review. Most of the conversation entails Roberta discussing the reasons she and her team pursued the issue of screening done by frontline treaters among a high-risk patient group, and in this case, patients with Type-2 diabetes in the northwest area of London. She describes all the key elements of the paper, from how the group selected patients to screen and how to screen them to then what the researchers learned in the process of doing the study. When she finishes, Jörn commends the study and notes that the results described are similar to what he has seen when evaluating patients in this clinic
With that as a very brief introduction to a fascinating conversation well-worth a listen, surf on to learn more about Roberta and critical ideas around screening strategies and much more. If you have questions or comments stemming from this episode, or any others for that matter, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
This week on SurfingNASH, we introduce the audience to new guest, Dr Roberta Forlano, who's been awarded an EASL Juan Rodes PhD Fellowship and has completed a PhD in Translational Hepatology at Imperial college London in 2022. Her current research interest are screening strategies for NAFLD in primary care, automated quantitation of histological features , lifestyle management, CV risk assessment and non-invasive markers in NAFLD. These interests and much more are shared and discussed with Jörn Schattenberg, Louise Campbell and Roger Green in a compelling episode with an overarching theme focusing on screening strategies for gender-based SLD challenges. To offer an example of how immensely productive and busy Roberta and her team have been, they recently presented 6 posters at the recently concluded SLD Summit.
With that as a very brief introduction to a fascinating conversation well-worth a listen, surf on to learn more about Roberta and critical ideas around screening strategies and much more. If you have questions or comments stemming from this episode, or any others for that matter, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
This week, SurfingNASH offers an episode comprising two seperate interviews which focus on stories around career trajectories, transitions and entrepreneurship. Host Roger Green talks with Rachel Zayas (AGED Diagnostics) and Michelle Long (Novo Nordisk) about their unique stories and creating new opportunities amidst a field with broadening but sometimes opaque horizons. These discussions will be very informative for those who may be wondering about what's on the other side, whether it be commercial medicine or academia. Surf on to learn more as Rachel and Michelle expand on bridging these gaps, managing challenges and their excitement for new ways forward.
In this final section of our interview with Michelle, we focus on the advice that Michelle would give a person in academia who wants to consider a corporate career and, conversely, what she now looks for in a corporate candidate coming from academia. Finally, Michelle discusses how she expects to spend the bulk of her research and conference time over the next year.
If you have questions or comments around these interviews or any of the topics discussed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
This week, SurfingNASH offers an episode comprising two seperate interviews which focus on stories around career trajectories, transitions and entrepreneurship. Host Roger Green talks with Rachel Zayas (AGED Diagnostics) and Michelle Long (Novo Nordisk) about their unique stories and creating new opportunities amidst a field with broadening but sometimes opaque horizons. These discussions will be very informative for those who may be wondering about what's on the other side, whether it be commercial medicine or academia. Surf on to learn more as Rachel and Michelle expand on bridging these gaps, managing challenges and their excitement for new ways forward.
This conversation with Michelle shifts focus to why she considers herself to have been naïve about commercial life. She then talks about the traits and characteristics that make an individual a good candidate to succeed and enjoy being in industry, and alternatively, the characteristics that suggest an individual might not enjoy it so much or perform as well.
If you have questions or comments around these interviews or any of the topics discussed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
This week, SurfingNASH offers an episode comprising two seperate interviews which focus on stories around career trajectories, transitions and entrepreneurship. Host Roger Green talks with Rachel Zayas (AGED Diagnostics) and Michelle Long (Novo Nordisk) about their unique stories and creating new opportunities amidst a field with broadening but sometimes opaque horizons. These discussions will be very informative for those who may be wondering about what's on the other side, whether it be commercial medicine or academia. Surf on to learn more as Rachel and Michelle expand on bridging these gaps, managing challenges and their excitement for new ways forward.
This conversation features the first part of our interview with Novo Nordisk International Medical Vice President, Michelle Long. The discussion focuses on the process by which Michelle came to leave academia and transition to corporate life. Along the way, she covers the importance of mentorship as well as deeply understanding what an individual finds exciting about a career in academia and, more specifically in Michelle’s case, academic research.
If you have questions or comments around these interviews or any of the topics discussed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
This week, SurfingNASH offers an episode comprising two seperate interviews which focus on stories around career trajectories, transitions and entrepreneurship. Host Roger Green talks with Rachel Zayas (AGED Diagnostics) and Michelle Long (Novo Nordisk) about their unique stories and creating new opportunities amidst a field with broadening but sometimes opaque horizons. These discussions will be very informative for those who may be wondering about what's on the other side, whether it be commercial medicine or academia. Surf on to learn more as Rachel and Michelle expand on bridging these gaps, managing challenges and their excitement for new ways forward.
This final part of Roger’s interview with Rachel shifts quickly from a discussion around fundraising to one about intentionality. Rachel shares the journey of how her company began with focus on hepatocellular carcinoma, the listening process that led to a refocus on NASH and NAFLD, and some of the opportunities that have accrued as a result of this switch. The rest of the conversation exemplifies the importance of strategic partnerships by focusing on AGED’s partnership with the US Department of Defense through the Henry Jackson Foundation.
If you have questions or comments around these interviews or any of the topics discussed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
This week, SurfingNASH offers an episode comprising two seperate interviews which focus on stories around career trajectories, transitions and entrepreneurship. Host Roger Green talks with Rachel Zayas (AGED Diagnostics) and Michelle Long (Novo Nordisk) about their unique stories and creating new opportunities amidst a field with broadening but sometimes opaque horizons. These discussions will be very informative for those who may be wondering about what's on the other side, whether it be commercial medicine or academia. Surf on to learn more as Rachel and Michelle expand on bridging these gaps, managing challenges and their excitement for new ways forward.
This conversation with Rachel returns to focus on fundraising and what it takes to win a new venture competition. She expands on the idea that fundraising is a two-way exploration to see whether the investor and investee company can function as partners in the development process. She also goes on to describe how competitions work and what transpired in the recent Pepperdine University School of Business competition that AGED Diagnostics won. Lastly, Rachel shares her thoughts on how and why ventures benefit from doing well in competitions even if there is no prize per se beyond the recognition of winning.
If you have questions or comments around these interviews or any of the topics discussed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
This week, SurfingNASH offers an episode comprising two seperate interviews which focus on stories around career trajectories, transitions and entrepreneurship. Host Roger Green talks with Rachel Zayas (AGED Diagnostics) and Michelle Long (Novo Nordisk) about their unique stories and creating new opportunities amidst a field with broadening but sometimes opaque horizons. These discussions will be very informative for those who may be wondering about what's on the other side, whether it be commercial medicine or academia. Surf on to learn more as Rachel and Michelle expand on bridging these gaps, managing challenges and their excitement for new ways forward.
This first conversation features a section of the interview with Rachel. While we originally planned for the interview to be largely about fundraising and what it takes to win new venture competitions, it didn’t quite turn out that way. After an initial question about fundraising, the two quickly refocus on Rachel’s product development process and the clinical trial work she is doing in preparation for market. Along the way, she describes the thinking behind designing her basic trial specifications and the sequential steps she has taken toward the 2,000 that will be her pivotal effort in obtaining approvals and coming to market.
If you have questions or comments around these interviews or any of the topics discussed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
This week, SurfingNASH offers an episode comprising two seperate interviews which focus on stories around career trajectories, transitions and entrepreneurship. Host Roger Green talks with Rachel Zayas (AGED Diagnostics) and Michelle Long (Novo Nordisk) about their unique stories and creating new opportunities amidst a field with broadening but sometimes opaque horizons. These discussions will be very informative for those who may be wondering about what's on the other side, whether it be commercial medicine or academia. Surf on to learn more as Rachel and Michelle expand on bridging these gaps, managing challenges and their excitement for new ways forward.
If you have questions or comments around these interviews or any of the topics discussed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
This episode From the Vault comes from last year's SurfingNASH review of the 2022 NAFLD Summit with Mazen Noureddin, Sven Francque and Hannes Hagström.
The 2022 NAFLD Summit uniquely presented a range of perspectives and insights on fatty liver and metabolic diseases.
Program speakers Mazen Noureddin, Sven Francque and Hannes Hagström join Surfer, Roger Green, on site from Dublin to review their reactions immediately after the conference ended. At the outset of this episode, the group discusses the benefits of participating in a smaller conference more focused on the challenges presented by the field of NAFLD. Mazen likens the NAFLD Summit to NASH-TAG, asserting that these specific conferences advance the field and address deeper layers around the issues that matter most. “You start being provocative.”
Mazen goes on to raise the issue of glycemic control and the impact of glycemic control on NASH drug performance. This bleeds into a brief point about the value of simply stopping fibrosis progression instead of the need to prove regression. He then identifies two sessions he considered particularly valuable: the Saturday morning autopsy of failed Phase 3 trials and therapeutic discussion about drugs at different stages in development. This segues into a discussion of optimism which can derive from the recent Akero and Altimmune results. In terms of Altimmune, Mazen asks whether the drug should go directly from Phase 1b to Phase 3. In general, the group believes that Phases 2a and 2b have value here. The panel agrees that the presentations on three failed Phase 3 trials were richly valuable and that each offered its own clear lessons for researchers.
The EASL SLD Summit aims at updating a global community of liver stakeholders on the most recent advances in SLD research, both pre-clinically and clinically, focusing on MASLD and tackling the issue of MetALD.
In this episode, Jörn Schattenberg, Louise Campbell and Roger Greenreview the recently concluded meeting with faculty members Sven Francque and Hannes Hagström in two seperate interviews.
This final conversation starts with Roger’s observation that one reason the energy in this meeting might have been higher is sessions like this one, that was less about sharing answers and more about identifying new topics and raising questions. Jörn segues to a talk he gave on weight loss and bariatric surgery and what it might mean for how we consider and treat MASLD patients. Louise asks whether the audience for this meeting was more diverse than in previous years, specifically mentioning the Society of Obesity. Jörn mentions that the impact of the video stream made the meeting far more accessible than in past years. Hannes notes he would like to hear questions from different specialists and more general physicians and surgeons than in years past. Roger notes that he saw more cardiovascular discussion than in prior years, and also perhaps speakers from more geographic regions. Roger also mentions a session on new techniques and their pitfalls and promises. Jörn notes that the outcomes from this basic science will define the targets for future drug research. The rest of the conversation revolves around the impact of making our focus less liver-specific and more metabolic or multi-organ. In closing, Louise asks what came up that we can use today and Hannes goes back to diagnostic pathways and FIB-4.
Listen to the full episode to gain a richer understanding than can be described in this summary. If you have questions or comments around the Summit or any other themes addressed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
The EASL SLD Summit aims at updating a global community of liver stakeholders on the most recent advances in SLD research, both pre-clinically and clinically, focusing on MASLD and tackling the issue of MetALD.
In this episode, Jörn Schattenberg, Louise Campbell and Roger Greenreview the recently concluded meeting with faculty members Sven Francque and Hannes Hagström in two seperate interviews.
This conversation featuring Hannes starts with him discussing a couple of very exciting projects that his lab at the Karolinska Institute is working on now. After which, Roger asks Hannes and Jörn to discuss why the energy in this meeting - especially as the debut SLD Summit - felt more vibrant to them than last year’s NAFLD Summit. Jörn comments that the broader aperture afforded by the new nomenclature led to talks on a wider variety of subjects than in previous years. Hannes notes three new areas of focus: first alcohol, second, problems with biopsy and third, a transition from ordinal variables (or what Hannes describes as the human tendency to categorize everything) to using more of a continuous spectrum to categorize MASH and fibrosis. Jörn notes how important this redefinition of variables is in terms of creating analytical error. The next couple of minutes include a conversation on how to consider MetALD in the context of alcoholic and nonalcoholic liver disease. Jörn then discusses a session at which he spoke on Sunday, a look at new mechanisms of action titled “Beyond the Usual Suspects.”
With that, listen to the full episode to gain a richer understanding than can be described in this summary. If you have questions or comments around the Summit or any other themes addressed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
From the official EASL SLD Summit website:
The EASL SLD Summit aims at updating a global community of liver stakeholders on the most recent advances in SLD research, both pre-clinically and clinically, focusing on MASLD and tackling the issue of MetALD. You will gain insights in the most key techniques employed in research, clinical trials and clinical practice, with an understanding of their potential as well as limitations. You will learn about the most recent advances in our understanding of the disease, including the role of sexual dimorphism, circadian clock or vascular mechanisms, and potential new targets as well as modalities of treatment. You will exchange on these topics with both young fellows and established experts in the field in a highly interactive format with a lot of room for discussion. You will get the latest update on where we stand with the efforts of having MASLD, and SLD in general, on the agenda as a public health problem and the roadmap and policies to tackle this problem, in which the people living with SLD, and many stakeholders have been increasingly joining forces. In light of the latter, the Summit will also provide a space to further discuss the nomenclature change and its potential impact on research clinical practice and awareness. A session will be dedicated to discussing in-depth the issue of people who combine alcohol use and metabolic risk factors, designated as MetALD in the latest nomenclature. You will also get the latest data on diagnosis and prognostication in MASH and on how to tackle MASLD as a multisystem disease, informing you not only on what you need to do, but also on the science and evidence behind it.
The EASL SLD Summit aims at updating a global community of liver stakeholders on the most recent advances in SLD research, both pre-clinically and clinically, focusing on MASLD and tackling the issue of MetALD.
In this episode, Jörn Schattenberg, Louise Campbell and Roger Greenreview the recently concluded meeting with faculty members Sven Francque and Hannes Hagström in two seperate interviews.
This final conversation from our interview with Sven centers on the research that Sven and his colleagues presented at the SLD Summit. Most of this research focuses on portal pressures in pre-cirrhotic patients, including those with fibrosis levels as low as F0 or F1. Sven notes that relatively few of these patients have elevations of 10mmHg or more in these earlier stage scenarios, but a significant number have elevations from 5-9 mmHG, which might affect health in more subtle ways. Roger asks about the impact of this work on how we treat patients today and into the future. Sven follows up by identifying several areas for future research. As the groups moves toward the end of the interview, Louise asks questions around using NITs, notably FibroScan, to check for pressures because in some of her work, VCTE in biopsied and non-biopsied livers demonstrated different results. Sven congratulates Louise on the question and indicates this might be a powerful area for future research.
With that, listen to the full episode to gain a richer understanding than can be described in this summary. If you have questions or comments around the Summit or any other themes addressed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
From the official EASL SLD Summit website:
The EASL SLD Summit aims at updating a global community of liver stakeholders on the most recent advances in SLD research, both pre-clinically and clinically, focusing on MASLD and tackling the issue of MetALD. You will gain insights in the most key techniques employed in research, clinical trials and clinical practice, with an understanding of their potential as well as limitations. You will learn about the most recent advances in our understanding of the disease, including the role of sexual dimorphism, circadian clock or vascular mechanisms, and potential new targets as well as modalities of treatment. You will exchange on these topics with both young fellows and established experts in the field in a highly interactive format with a lot of room for discussion. You will get the latest update on where we stand with the efforts of having MASLD, and SLD in general, on the agenda as a public health problem and the roadmap and policies to tackle this problem, in which the people living with SLD, and many stakeholders have been increasingly joining forces. In light of the latter, the Summit will also provide a space to further discuss the nomenclature change and its potential impact on research clinical practice and awareness. A session will be dedicated to discussing in-depth the issue of people who combine alcohol use and metabolic risk factors, designated as MetALD in the latest nomenclature. You will also get the latest data on diagnosis and prognostication in MASH and on how to tackle MASLD as a multisystem disease, informing you not only on what you need to do, but also on the science and evidence behind it.
The EASL SLD Summit aims at updating a global community of liver stakeholders on the most recent advances in SLD research, both pre-clinically and clinically, focusing on MASLD and tackling the issue of MetALD.
In this episode, Jörn Schattenberg, Louise Campbell and Roger Greenreview the recently concluded meeting with faculty members Sven Francque and Hannes Hagström in two seperate interviews.
This conversation starts with Roger asking Sven for his impression about whether the three diseases - MASH, MetALD, Alcoholic SLD - lie on a single continuum or whether the alcoholic and non-alcoholic causes of disease are separate dimensions. Sven suggests that there are different dimensions that can be seen in elements of hepatic structure and vascularization, but that neither are completely independent. Switching to a different challenge around MetALD and alcohol, Jörn discusses the complexity in patients assessing their own drinking behaviors given that much drinking is a weekend-oriented social event rather than a consistent pattern of daily consumption. In the course of this discussion, both Sven and Jörn note their hope that AI/ML will provide pivotal new insights on these issues. Sven comments that he hopes that research will continue to develop along a path of basic science rather than simple drug testing and development. Roger suggests that the relatively low level of efficacy with late stage development drug suggests that we need to learn far more about the basic science to support development of highly successful drugs and NITs.
With that, listen to the full episode to gain a richer understanding than can be described in this summary. If you have questions or comments around the Summit or any other themes addressed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
From the official EASL SLD Summit website:
The EASL SLD Summit aims at updating a global community of liver stakeholders on the most recent advances in SLD research, both pre-clinically and clinically, focusing on MASLD and tackling the issue of MetALD. You will gain insights in the most key techniques employed in research, clinical trials and clinical practice, with an understanding of their potential as well as limitations. You will learn about the most recent advances in our understanding of the disease, including the role of sexual dimorphism, circadian clock or vascular mechanisms, and potential new targets as well as modalities of treatment. You will exchange on these topics with both young fellows and established experts in the field in a highly interactive format with a lot of room for discussion. You will get the latest update on where we stand with the efforts of having MASLD, and SLD in general, on the agenda as a public health problem and the roadmap and policies to tackle this problem, in which the people living with SLD, and many stakeholders have been increasingly joining forces. In light of the latter, the Summit will also provide a space to further discuss the nomenclature change and its potential impact on research clinical practice and awareness. A session will be dedicated to discussing in-depth the issue of people who combine alcohol use and metabolic risk factors, designated as MetALD in the latest nomenclature. You will also get the latest data on diagnosis and prognostication in MASH and on how to tackle MASLD as a multisystem disease, informing you not only on what you need to do, but also on the science and evidence behind it.
The EASL SLD Summit aims at updating a global community of liver stakeholders on the most recent advances in SLD research, both pre-clinically and clinically, focusing on MASLD and tackling the issue of MetALD.
In this episode, Jörn Schattenberg, Louise Campbell and Roger Greenreview the recently concluded meeting with faculty members Sven Francque and Hannes Hagström in two seperate interviews.
The first featured interview is with Sven, who served as one of three organizing members for this year's Summit. In addition, Sven chaired both the opening and closing Plenary sessions on the subject of Metabolism, Alcohol and Toxicity. Sven also delivered a presentation titled Anti-platelet drugs in MASLD: pre-clinical and clinical data. This conversation starts with the co-hosts congratulating Sven on the success of the SLD summit program. In response to several questions, Sven discusses how the organizers began to shape a broader agenda even before the new nomenclature was adopted, and how they broadened further after its acceptance at the EASL Congress earlier in the year. Jörn responds that he felt the expanded focus made the meeting more robust and goes on to highlight the sections he liked best. After Roger asks about anticipated changes in future programs, Sven discusses the tremendous value he saw in having younger researchers present who in turn receive feedback from more senior colleagues. Louise concurs on this point before circling back to discuss the benefits of the MetALD disease classification.
With that, listen to the full episode to gain a richer understanding than can be described in this summary. If you have questions or comments around the Summit or any other themes addressed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
From the official EASL SLD Summit website:
The EASL SLD Summit aims at updating a global community of liver stakeholders on the most recent advances in SLD research, both pre-clinically and clinically, focusing on MASLD and tackling the issue of MetALD. You will gain insights in the most key techniques employed in research, clinical trials and clinical practice, with an understanding of their potential as well as limitations. You will learn about the most recent advances in our understanding of the disease, including the role of sexual dimorphism, circadian clock or vascular mechanisms, and potential new targets as well as modalities of treatment. You will exchange on these topics with both young fellows and established experts in the field in a highly interactive format with a lot of room for discussion. You will get the latest update on where we stand with the efforts of having MASLD, and SLD in general, on the agenda as a public health problem and the roadmap and policies to tackle this problem, in which the people living with SLD, and many stakeholders have been increasingly joining forces. In light of the latter, the Summit will also provide a space to further discuss the nomenclature change and its potential impact on research clinical practice and awareness. A session will be dedicated to discussing in-depth the issue of people who combine alcohol use and metabolic risk factors, designated as MetALD in the latest nomenclature. You will also get the latest data on diagnosis and prognostication in MASH and on how to tackle MASLD as a multisystem disease, informing you not only on what you need to do, but also on the science and evidence behind it.
The EASL SLD Summit aims at updating a global community of liver stakeholders on the most recent advances in SLD research, both pre-clinically and clinically, focusing on MASLD and tackling the issue of MetALD.
In this episode onSurfing NASH, Jörn Schattenberg, Louise Campbell and Roger Greenreview this recently concluded meeting with faculty members Sven Francque and Hannes Hagström. Jörn joins both guests as a fellow presenter and the group dives into program highlights with many fascinating takes and interplaying ideas.
The first featured interview is with Sven, who served as one of three organizing members for this year's Summit. In addition, Sven chaired both the opening and closing Plenary sessions on the subject of Metabolism, Alcohol and Toxicity. Sven also delivered a presentation titled Anti-platelet drugs in MASLD: pre-clinical and clinical data. The following feature with Hannes explores elements of his presentation on how common alcohol overconsumption is in MASLD and how highly this increases risk for future cirrhosis. Throughout both interviews, Jörn is able to elaborate and reflect on his high level of engagement at the Summit as he chaired an industry session and gave three presentations with subjects ranging from clinical trial data (MAESTRO-NASH for resmetirom) to endoscopic bariatric therapies and mitochondrial uncoupling.
With that, listen to the full episode to gain a richer understanding than can be described in this summary. If you have questions or comments around the Summit or any other themes addressed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
From the official EASL SLD Summit website:
The EASL SLD Summit aims at updating a global community of liver stakeholders on the most recent advances in SLD research, both pre-clinically and clinically, focusing on MASLD and tackling the issue of MetALD. You will gain insights in the most key techniques employed in research, clinical trials and clinical practice, with an understanding of their potential as well as limitations. You will learn about the most recent advances in our understanding of the disease, including the role of sexual dimorphism, circadian clock or vascular mechanisms, and potential new targets as well as modalities of treatment. You will exchange on these topics with both young fellows and established experts in the field in a highly interactive format with a lot of room for discussion. You will get the latest update on where we stand with the efforts of having MASLD, and SLD in general, on the agenda as a public health problem and the roadmap and policies to tackle this problem, in which the people living with SLD, and many stakeholders have been increasingly joining forces. In light of the latter, the Summit will also provide a space to further discuss the nomenclature change and its potential impact on research clinical practice and awareness. A session will be dedicated to discussing in-depth the issue of people who combine alcohol use and metabolic risk factors, designated as MetALD in the latest nomenclature. You will also get the latest data on diagnosis and prognostication in MASH and on how to tackle MASLD as a multisystem disease, informing you not only on what you need to do, but also on the science and evidence behind it.
If you missed this year's Paris NASH meeting, you missed some exciting presentations featuring fresh, pivotal insights about Fatty Liver diseases and some new approaches to learning about this disease. For this episode From the Vault, we take a look back at what has by far been the most downloaded episode in the history of the podcast: S2-E46 - Highlights from Paris NASH 2021. Jörn Schattenberg and Stephen Harrison combine to provide a robust synopsis of the meeting while Roger Green asks a few questions and keeps the discussion in-bounds:
10:20 – Jörn introduces Paris NASH and discusses some of its basics, followed by introduction of Session 1: Epidemiology and the Public Response
14:07 – Stephen discusses potential for integrating home healthcare visits into clinical trials
17:15 – Session 2: Clinical Aspects
17:52 – “NASH does come in different flavors.” Are we thinking about NASH with sufficient granularity?
20:32 – NASH pathogenesis and its link to other metabolic diseases
21:32 – Session 3: Deep dive into fibrosis
24:30 – Talk on “Innovations in imaging assessment in fibrosis” raises pivotal questions about advances we can make in cellular-level understanding
26:57 – Talk from Scott Friedman on “Common mechanisms, molecular evolution and resolution of fibrosis in NASH” yields several key ideas
28:45 – The importance of understanding stellate cell subtypes
33:37 – Jörn and Stephen select some key moments from Day Two
35:45 – Innovations in clinical trial bring researchers to consider competing risks and challenges in determining causes of mortality in NASH trials
40:26 – Session 8, “Global NASH,” describes the size and scale of the NASH challenge around the world
If you have questions or comments around the contents of this episode or the FDA workshop on NITs, drug development or any other themes addressed in this week, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
In Season 4, Episode 41, the surfers (Jörn Schattenberg, Louise Campbell and Roger Green) review highlights from the FDA's NIT workshop in three seperate interview sessions with guests Naim Alkhouri, Laurent Castera and Veronica Miller. Each guest participated in some form at the meeting and shares slightly differing but incredibly insightful perspectives.
This conversation is the first part of the Surfer’s interview with Veronica. Veronica starts by commending FDA for organizing the workshop and indicates that now we all need to process the data. Roger asks Veronica what FDA might have done better, and she indicates they might have offered more feedback about how far they feel the field has come. She notes that there are many steps ahead and that the FDA needs to be more cautious. She also felt that the mix of data presentations and panel discussions worked well. She points to ballooning and its challenges as the clearest point needing change and then went back to Dr. Johnson’s question about “why are we validating a surrogate with a surrogate?” Roger shares a comment from S1E12 after the first OCA Complete Response Letter and how a regulatory consultant elicited a strong reaction from Stephen Harrison for the same comment. This leads Louise to ask whether we should look to broaden our target outcomes beyond the liver. Veronica notes that we have traditionally looked in an organ-specific way but wonders whether the new nomenclature will focus more attention on metabolic disease, although the topic was not really addressed. As the conversation ends, Roger asks Veronica whether approaches like NAIL-NIT respond to the “surrogate of a surrogate” question. Veronica says that might be right and that other groups like NIMBLE and LITMUS are looking at similar issues, although they sometimes compare to biopsy (which is what drove the surrogate of a surrogate comment in the first place.)
Plenty more ideas are explored as this is both a fascinating and pivotal workshop which covers a range of topics on NITs with presentations by the some of the field's most innovative and knowledgable contributors. If you have questions or comments around the workshop, NITs, drug development or any other themes addressed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
In Season 4, Episode 41, the surfers (Jörn Schattenberg, Louise Campbell and Roger Green) review highlights from the FDA's NIT workshop in three seperate interview sessions with guests Naim Alkhouri, Laurent Castera and Veronica Miller. Each guest participated in some form at the meeting and shares slightly differing but incredibly insightful perspectives.
This conversation begins with discussing a point from a previous episode in 2022 about the difference between NITs to qualify patients for trials versus to evaluate efficacy of drugs. This point stems from the idea that the way disease regresses may not be the same way it progresses. Laurent notes that NIMBLE and LITMUS have demonstrated important results with large data over the last two years. Jörn comments on the limits of using transaminase as a key NIT and Laurent replies by discussing a study over time that shows faster early declines on liver stiffness and slow declines over time as therapy might shift from reducing inflammation to regressing fibrosis. Louise shifts focus to ask about the relationship between kilopascal drops related to lifestyle change, specifically to ask whether these are false positives or real effects. Laurent notes that BMI is a confounder for liver stiffness and that CAP might help assess this issue. Finally, in response to a question from Louise, Laurent answers that we do not know about some of the key changes in test scores, and need to know more.
Plenty more ideas are explored as this is both a fascinating and pivotal workshop which covers a range of topics on NITs with presentations by the some of the field's most innovative and knowledgable contributors. If you have questions or comments around the workshop, NITs, drug development or any other themes addressed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
In Season 4, Episode 41, the surfers (Jörn Schattenberg, Louise Campbell and Roger Green) review highlights from the FDA's NIT workshop in three seperate interview sessions with guests Naim Alkhouri, Laurent Castera and Veronica Miller. Each guest participated in some form at the meeting and shares slightly differing but incredibly insightful perspectives.
This conversation introduces the first part of an interview with Laurent Castera. Roger starts by asking Laurent how he, as one of the few non-American presenters, felt about the meeting. Laurent noted how important the meeting was given that it came from FDA, which the entire world looks to on drug approvals. Jörn notes that his general sense of the meeting is that while researchers have made significant progress with NIT research, particularly around ballooning, FDA might require more data. Laurent concurs, using the pithy statement “inflammation is a driver, liver fibrosis is a killer and steatosis is a marker.” He goes on to discuss the Brunt paper on ballooning before describing that he finds himself concerned that if biopsy is a bottleneck to approval, ballooning is the issue that might limit the number of patients approved for the drug. He sees this as a problem given how confounded the variable is. He closes this comment by noting that while we might have strong biomarkers for fibrosis, we do not seem to have such strength for NASH or drug response. Roger goes on to describe ideas from the past podcast conversation from Season 3 Episode 14 and whether the best next step is to redefine the ballooning variable. Jörn shares an argument from the workshop that if it is so hard for biopsy to measure the necessary variable, why don’t we simply use the NIT? He also asks Laurent to comment on some unpublished data that Laurent was given permission by Dr. Vincent Wong to share at the meeting. Since the data is unpublished, it will not be described in this summary except to say that it appears extremely important and powerful and, hopefully, will pass review and be published later this year.Plenty more ideas are explored as this is both a fascinating and pivotal workshop which covers a range of topics on NITs with presentations by the some of the field's most innovative and knowledgable contributors. If you have questions or comments around the workshop, NITs, drug development or any other themes addressed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
In Season 4, Episode 41, the surfers (Jörn Schattenberg, Louise Campbell and Roger Green) review highlights from the FDA's NIT workshop in three seperate interview sessions with guests Naim Alkhouri, Laurent Castera and Veronica Miller. Each guest participated in some form at the meeting and shares slightly differing but incredibly insightful perspectives.
Roger starts this conversation by discussing loss aversion – the idea that an individual’s decision does not reflect an overall fear of risk, but a specific fear of risking something they do not want to lose. Researchers and advocates define loss in terms of time to bring a drug to market or screen fail rates, but for government regulators, “loss” can refer to prestige or credibility when they make what are publicized as “wrong decisions.” Naim registers the issue, but notes that in his clinic, no more than 5% of people test in a way that might qualify them for clinical trials, and probably 1-2% ever participate altogether. He contrasts the high percentage of population with identifiable MASH (which might be 15%) with the 1 in 1,000 “unicorns” in the population that can qualify for trials, suggesting this demonstrates how strongly we need to reconsider testing standards and protocols. Jörn mentions that the FDA commentator in the final session suggested we avoid surrogates altogether and instead look into a million person trial. Naim agrees that this is not feasible. From here, the group moves to other issues, including cause of death among patients with F0 to F3 fibrosis. As the conversation continues, Louise comments on the idea of doing broader, multi-organ or multi-outcome trials with drugs, as have been done with vitamins. She ends her comment by stating, “I would rather go into the future making the wrong decisions for the right reasons than the right decisions for the wrong reasons.” This statement represents a broader look at how we approve MASH drugs. Naim and Jörn both agree. In the last part of this conversation, Roger asks what Naim anticipates FDA might do next. Naim talks about studies generating more data with more NITs that might lead to what he describes as his “dream” – continuing the biopsy pathway but providing one alternative pathway based on a combination of NITS.
Plenty more ideas are explored as this is both a fascinating and pivotal workshop which covers a range of topics on NITs with presentations by the some of the field's most innovative and knowledgable contributors. If you have questions or comments around the workshop, NITs, drug development or any other themes addressed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
In Season 4, Episode 41, the surfers (Jörn Schattenberg, Louise Campbell and Roger Green) review highlights from the FDA's NIT workshop in three seperate interview sessions with guests Naim Alkhouri, Laurent Castera and Veronica Miller. Each guest participated in some form at the meeting and shares slightly differing but incredibly insightful perspectives.
This conversation covers the first part of our interview with Naim, who served as an expert panelist in Tuesday’s penultimate session. The conversation starts with Naim commending the session and noting that what drug developers and principal investigators truly are seeking is an NIT-based alternative path to conditional approval. Jörn’s response notes that the current alternative – biopsy to measure fibrosis level and NAS activity score – is imperfect, as would be an NIT approach at this time, but notes that he is not certain FDA sees the issue that way. Louise notes and commends Naim for the passion with which he made his case at the meeting. From here, Naim points out that the current system denies care or trial participation to people with clear NASH if the researcher cannot identify ballooning in the initial biopsy. Jörn suggests, and Naim agrees, that NITs need to be selected with an eye toward drug mode of action and markers. He specifically points out the value of MR technology and why he finds it superior to VCTE.
Plenty more ideas are explored as this is both a fascinating and pivotal workshop which covers a range of topics on NITs with presentations by the some of the field's most innovative and knowledgable contributors. If you have questions or comments around the workshop, NITs, drug development or any other themes addressed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
[Meeting Information from the FDA Website]
Drug development for NASH/MASH with liver fibrosis has increased substantially and there is growing interest in developing NITs to detect the presence of fibrosis, and to accurately classify different stages of fibrosis as well as cirrhosis. Candidate NITs include both blood tests (circulating biomarkers) and imaging tests. In recent years, most data regarding use of NITs have been collected from NASH/MASH clinical trials. However, there are limited published data for use of NITs across the spectrum of the affected population that would be encountered in routine clinical care, including patients without fibrosis. This workshop will assist the FDA in identifying current knowledge gaps for using NITs as diagnostic biomarkers and reasonably likely surrogates, as well as provide a framework for additional data that are needed to fill these knowledge gaps. Ultimately, the FDA seeks to learn whether expert stakeholders have evidence to indicate currently available NITs are adequate to meet the Agency evidentiary standard for assessing primary evidence of clinical efficacy. The primary focus of this workshop is “non-cirrhotic NASH/MASH population with advanced (i.e., Stage 2 or Stage 3) liver fibrosis”. The workshop will not address the use of biomarkers for treatment trials in cirrhosis due to NASH/MASH, however, the workshop will discuss identification of “progression to cirrhosis” using biomarkers.
On September 18-19, the FDA hosted a workshop to update key stakeholders on the state-of-the-art use of biomarkers and noninvasive tests (NITs) based on recent advances in NASH/metabolic dysfunction associated steatohepatitis (MASH) clinical trials. In this episode, Surfing NASH reviews highlights from the workshop in three seperate interview sessions with guests Naim Alkhouri, Laurent Castera and Veronica Miller. Each guest participated in some form at the meeting and shares slightly differing but incredibly insightful perspectives with Surfers Jörn Schattenberg, Louise Campbell and Roger Green. Naim elaborates on the limitations of current pathways and the possibilities of combination NITs and conditional approval. Laurent discusses "inflammation as disease a driver, liver fibrosis as a killer and steatosis as a marker." Veronica shares thoughts around collaboration and expanding this conversation on NITs to move the field forward. Additionally, plenty more ideas are explored as this is a very fascinating and pivotal workshop which covers a range of topics on NITs with presentations by the some of the field's most innovative and knowledgable contributors. Listen to the full episode to gain a richer understanding than can be described in this summary. If you have questions or comments around the workshop, NITs, drug development or any other themes addressed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
[Meeting Information from the FDA Website]
Use of Biomarkers for Diagnosing and Assessing Treatment Response in Noncirrhotic NASH Trials
Drug development for NASH/MASH with liver fibrosis has increased substantially and there is growing interest in developing NITs to detect the presence of fibrosis, and to accurately classify different stages of fibrosis as well as cirrhosis. Candidate NITs include both blood tests (circulating biomarkers) and imaging tests. In recent years, most data regarding use of NITs have been collected from NASH/MASH clinical trials. However, there are limited published data for use of NITs across the spectrum of the affected population that would be encountered in routine clinical care, including patients without fibrosis. This workshop will assist the FDA in identifying current knowledge gaps for using NITs as diagnostic biomarkers and reasonably likely surrogates, as well as provide a framework for additional data that are needed to fill these knowledge gaps. Ultimately, the FDA seeks to learn whether expert stakeholders have evidence to indicate currently available NITs are adequate to meet the Agency evidentiary standard for assessing primary evidence of clinical efficacy. The primary focus of this workshop is “non-cirrhotic NASH/MASH population with advanced (i.e., Stage 2 or Stage 3) liver fibrosis”. The workshop will not address the use of biomarkers for treatment trials in cirrhosis due to NASH/MASH, however, the workshop will discuss identification of “progression to cirrhosis” using biomarkers.
Along with NASH-TAG, Paris NASH is one of two famously small, science-based and publicly available events every year for the liver community. Given the depth of topics and ideas explored in Paris, the event in its entirety would be nearly impossible to cover in a single conclusive episode. That said, the Surfers (Jörn Schattenberg, Louise Campbell and Roger Green) are joined by two presenting KOLs, Scott Friedman and Laurent Castera, for a neatly packaged conversation to capture some of the key dynamics of the meeting. Particularly, the group hone in on developments in the landscape around NITs.
This wrap-up conversation starts with Roger asking the panelists what other important/intriguing questions we have not yet covered which arose in the meeting. Scott discusses interesting talks on genetics. Laurent concurs and adds that he was struck by a talk about pediatric NASH, which is more likely to be endogenous since these young patients do not consume alcohol, but also confounded by how pediatricians are trained (or rather, not trained) to conduct biopsies and otherwise assess patients. Jörn discusses a statistical method for comparing disparate options known as DOOR – Desirability of Outcome Rankings. Lastly, Louise and Roger raise a couple of additional questions. Listen on to hear what they are.This episode and its conversations cover a range of fascinating insights stemming from yet another impactful Paris NASH meeting. If you have questions or comments around Paris NASH, NITs or any other themes addressed, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
Along with NASH-TAG, Paris NASH is one of two famously small, science-based and publicly available events every year for the liver community. Given the depth of topics and ideas explored in Paris, the event in its entirety would be nearly impossible to cover in a single conclusive episode. That said, the Surfers (Jörn Schattenberg, Louise Campbell and Roger Green) are joined by two presenting KOLs, Scott Friedman and Laurent Castera, for a neatly packaged conversation to capture some of the key dynamics of the meeting. Particularly, the group hone in on developments in the landscape around NITs.
This conversation starts with a question from Louise about whether utilizing CAP would provide added insight in light of what the group has discussed around NITs in the preceding conversations. Laurent responds that CAP is more related to inflammation and steatosis than to fibrosis, and Scott agrees. Laurent suggests that MRI-PDFF would be an ideal test for addressing this issue, but it is not cost-effective for regular practice. Therefore, he uses VCTE measures, including CAP, because the numbers he provides are motivating to patients. Louise asks how activation of stellate cells depends on disease and Scott notes that most stellate cell activation is driven by inflammation, not fat. However, this raises two challenges: whether lipotoxic mediators drive fibrosis directly or act through inflammation and, more broadly, that current clinical tools for measuring fat are quite broad. On this point, Jörn notes that as the liver progresses toward cirrhosis, it loses fat and thus makes the entire issue more complex. Roger raises the question whether patient compliance and adherence might be affected negatively by uncertainty about the meaning of results. The rest of this conversation centers around Scott’s comment about the complicated impact of using GLP-1s and other incretins to treat obesity will have on Steatotic Liver Disease (SLD) and challenges in treating and assessing adequately.
This episode and its conversations cover a range of fascinating insights stemming from yet another impactful Paris NASH meeting. If you have questions or comments around Paris NASH, NITs or any other themes addressed, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
Along with NASH-TAG, Paris NASH is one of two famously small, science-based and publicly available events every year for the liver community. Given the depth of topics and ideas explored in Paris, the event in its entirety would be nearly impossible to cover in a single conclusive episode. That said, the Surfers (Jörn Schattenberg, Louise Campbell and Roger Green) are joined by two presenting KOLs, Scott Friedman and Laurent Castera, for a neatly packaged conversation to capture some of the key dynamics of the meeting. Particularly, the group hone in on developments in the landscape around NITs.
This conversation begins with Jörn discussing his topic from Paris NASH. His notes stem from a topic he received from the organizers: once a drug is available in the clinic, which test will you use to decide if the patient gets the drug. Jörn notes quickly that he will use neither biopsy nor FIB-4. He then notes that FAST was designed for this purpose, but that no current test makes sense today. Scott raises the parallel question: once you commit a patient to therapy, how will you determine whether the patient is responding or not? Jörn notes that most of the data we see today is aggregate, rather than the individual patient data we will need to assess how each patient performs on these tests. Laurent notes that there is not much data on this issue and then goes on to discuss the one study that does exist. He also describes a two-stage decline in test scores over time, with a more robust early decline and a slower decline later. That said, he questions whether the reduction in stiffness results from a decline in inflammation or fibrosis.
As the conversation winds down the floor goes back to Scott and Jörn. Scott notes that while the question is interesting, declines in inflammation or fibrosis both correlate with improved outcomes. He also notes that currently developing fibrosis-specific markers like ProC3 may help answer this question. Jörn says that the answer he gave in the meeting is a form of “it depends” – in this case, possibly on the starting level of drug, whether the decline is early or late stage and the starting fibrosis level.
This episode and its conversations cover a range of fascinating insights stemming from yet another impactful Paris NASH meeting. If you have questions or comments around Paris NASH, NITs or any other themes addressed, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
Along with NASH-TAG, Paris NASH is one of two famously small, science-based and publicly available events every year for the liver community. Given the depth of topics and ideas explored in Paris, the event in its entirety would be nearly impossible to cover in a single conclusive episode. That said, the Surfers (Jörn Schattenberg, Louise Campbell and Roger Green) are joined by two presenting KOLs, Scott Friedman and Laurent Castera, for a neatly packaged conversation to capture some of the key dynamics of the meeting. Particularly, the group hone in on developments in the landscape around NITs.
This session starts with questions to Laurent from Jörn and Louise about his comments on NITs from the preceding conversation. Jörn concurs with Laurent’s statements on the value of FIB-4, particularly if the provider conducts sequential tests. Louise asks whether we are looking solely at liver disease, given the high levels of non-liver mortality among patients with F1-F3 fibrosis. Laurent notes that the primary purpose so far has been to identify F3 and F4 NASH, but more recently methods such as FAST, MAST, MEFIB and MASEF, which was discussed on the podcast in S4E39, seek to define disease stages with greater specificity. He then goes on to discuss the importance of the context of screening on test performance. Laurent notes that in higher prevalence populations there will be a larger percentage of false positives. Thus, he notes, FIB-4 works well in initial screening based on strong NPV performance, but has less value in a disease-enriched population.
This episode and its conversations cover a range of fascinating insights stemming from yet another impactful Paris NASH meeting. If you have questions or comments around Paris NASH, NITs or any other themes addressed, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
Along with NASH-TAG, Paris NASH is one of two famously small, science-based and publicly available events every year for the liver community. Given the depth of topics and ideas explored in Paris, the event in its entirety would be nearly impossible to cover in a single conclusive episode. That said, the Surfers (Jörn Schattenberg, Louise Campbell and Roger Green) are joined by two presenting KOLs, Scott Friedman and Laurent Castera, for a neatly packaged conversation to capture some of the key dynamics of the meeting. Particularly, the group hone in on developments in the landscape around NITs.
This conversation starts with Scott discussing the session he shared with Fabio Marra which investigates the link between fibrosis and regeneration. Scott points out that the liver’s ability to regenerate is unique among organs and a pivotal question for which a new answer arises every ten years, none of which turns out to cover the topic adequately. He goes on to note that injured livers are less likely to regenerate and that regenerative livers are less likely to create scar. He suggests that while we do not know which one comes first, the answer is likely to have broad implications not only for liver disease but also a range of other organs. In response to a question from Roger, Scott says he considers it more likely that regenerating liver tissue sends a message to break down scarring. This inclination is based on thorough experience of observing the natural history of treating viral hepatitis. Jörn asks about the degree to which the underlying etiology of disease causes this response. Scott states that the response is fairly common across etiologies but, as he notes, the devil is in the details.
The rest of this conversation is devoted to Laurent and his session with Dr. Mark Muthiah about the use and limitations of NITs. This talk evolved from a case study about an individual patient. Laurent’s point, in a nutshell, is that we need a range of tests depending on the question we are trying to answer – initial screening vs. staging vs. monitoring - but that the entire issue runs the risk of overwhelming front-line treaters who are not aware of these issues. In this context, he sites the value of FIB-4, and also its major drawback related to ages and cutoffs.
This episode and its conversations cover a range of fascinating insights stemming from yet another impactful Paris NASH meeting. If you have questions or comments around Paris NASH, NITs or any other themes addressed, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
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Along with NASH-TAG, Paris NASH is one of two famously small, science-based and publicly available events every year for the liver community. Given the depth of topics and ideas explored in Paris, the event in its entirety would be nearly impossible to cover in a single conclusive episode. That said, the Surfers (Jörn Schattenberg, Louise Campbell and Roger Green) are joined by two presenting KOLs, Scott Friedman and Laurent Castera, for a neatly packaged conversation to capture some of the key dynamics of the meeting. Particularly, the group hone in on developments in the landscape around NITs.
This episode begins with Scott discussing the session he shared with Fabio Marra which investigates the link between fibrosis and regeneration. Scott points out that the liver's ability to regenerate is unique among organs and the question of how it does so is readdressed seemingly each passing decade without clear explanation. He goes on to note that injured livers are less likely to regenerate than healthy ones and that regenerative livers are less likely to scar. While we do not know which of these phenomena comes first, the answer is likely to have a broad range of implications not only for liver disease but also a range of other organs in addition.
Next, Laurent shares thoughts from his session with Mark Muthiah about the use and limitations of NITs. In a nutshell, Laurent explains why we need a range of tests to choose from depending on the question which we are looking for an answer. The reoccurring theme on the podcast around the importance of frontline education and training is addressed by Laurent here. Further, he underscores the value and simplicity behind FIB-4 as a simple frontline testing tool while also discussing its drawbacks. From here, Jörn and Louise ask relevant and interesting questions around what Laurent has discussed.
Jörn moves on to discuss the question that goes once a drug is approved, which test will you use to determine whether a patient receives that therapy or not? Jörn promptly notes thathe will use neither biopsy nor FIB-4 then comments that FAST was designed for this purpose, but doesn't rise to the level he would hope to find. Scott raises a parallel question that goes once you commit a patient to drug, how will it be determined that the patient is responding or not? The conversation continues to look into how to assess data at an individual level and learn more about how each patient variably responds to tests.
For a wrap up question, Roger asks for any other important or intriguing questions yet to be covered that arose in the meeting. Scott shares some interesting talks on genetics, while Laurent adds that he was struck powerfully by a talk on pediatric NASH. Jörn goes a different direction and discusses a statistical method for comparing disparate options known as DOOR, or desirability of outcome rankings, and its effect on how to compare drugs and different options in unique patient situations.
This conversation covers many more fascinating elements of another insightful Paris NASH meeting. Listen to the full episode and dive into this weekend's conversation to gain a richer understanding than can be described in this summary. If you have questions or comments around Paris NASH, NITs or any other themes addressed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
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Surfing NASH returns to its regular program with a fresh episode and some fascinating and progressive ideas around non-invasive testing. Mazen Noureddin joins co-hosts Jörn Schattenberg, Louise Campbell and Roger Green to discuss serum identification of at-risk MASH and the Metabolomics-Advanced Steatohepatitis Fibrosis Score (MASEF). In late July, Mazen co-authored a paper on the subject which was published in Hepatology.
This final conversation starts with Louise’s curiosity on whether any socioeconomic differences were clear between those considered at-risk. Mazen responds with his belief that there would be much to benefit from studying a larger prospective cohort with multiple different ethnic groups. Before moving on to final thoughts, Roger asks Mazen whether there are any populations yet to be considered that might benefit from this work going forward. Mazen responds by highlighting the importance of continued and persistent testing and reiterates that the next steps have more to do with response to therapy and correlation with outcomes. Jörn lastly mentions that the cirrhotic patient population would benefit from a test to which Mazen offers a clarifying response on when and why this group was included in the study.
In closing, Roger asks the group, starting with Mazen, to envision the practical use of MASEF two years from today. Each panelist provides a thought-provoking answer - surf on to learn more.
If you have questions or comments around MASEF, metabolomics or any other ideas considered in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com. The Surfing the NASH Tsunami will be back next week with more original content.
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Surfing NASH returns to its regular program with a fresh episode and some fascinating and progressive ideas around non-invasive testing. Mazen Noureddin joins co-hosts Jörn Schattenberg, Louise Campbell and Roger Green to discuss serum identification of at-risk MASH and the Metabolomics-Advanced Steatohepatitis Fibrosis Score (MASEF). In late July, Mazen co-authored a paper on the subject which was published in Hepatology.
This conversation begins with Louise’s focus on pediatric cohorts and whether MASEF can be applied to younger populations. Mazen states that while it has yet to be applied in this way, he would be very interested to learn more and invites anyone interested to reach out. From here Roger steers the discussion towards the future MASEF and what Mazen would like to have happen next in terms of its progress. Mazen notes the surprisingly fast commercial uptake of metabolomics tests and talks about how it might soon roll out in the US. Ultimately, he hopes if proven to be a good test that this will help replace biopsy.
The remainder of the conversation considers a question from Louise around how MASEF could be adapted for the newly classified Met-ALD (those with MASLD who consume greater amounts of alcohol per week).
If you have questions or comments around MASEF, metabolomics or any other ideas considered in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com. The Surfing the NASH Tsunami will be back next week with more original content.
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Surfing NASH returns to its regular program with a fresh episode and some fascinating and progressive ideas around non-invasive testing. Mazen Noureddin joins co-hosts Jörn Schattenberg, Louise Campbell and Roger Green to discuss serum identification of at-risk MASH and the Metabolomics-Advanced Steatohepatitis Fibrosis Score (MASEF). In late July, Mazen co-authored a paper on the subject which was published in Hepatology.
This conversation begins with Louise’s initial response around the setting of application for MASEF. She poses a question that leads the group to explore possible pros and cons of different approaches and the potential impact each might have in terms of cost effectiveness. For example, Jörn wonders how feasible it will be for non-experts to administer. Mazen suggests that its application will be relatively easy before explaining how to navigate the caveat of a gray zone similar to that of VCTE. After a few more comments on sequential pairing with FIB-4, Mazen next teases the possibility of demonstrating therapeutic efficacy in the drug development space.
Louise returns to a question around cohorts and asks whether variables like age or sex has an impact on the test’s capabilities. She then asks whether this sort of work has the potential to inform retrospective cardiac studies. After Mazen and Louise go back and forth with a few ideas in response, Roger makes the comment that he is struck by the wide breadth of application and describes the platform as “elegant.” As the conversation winds down, the group discusses a few comparisons between different blood-based markers.
If you have questions or comments around MASEF, metabolomics or any other ideas considered in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com. The Surfing the NASH Tsunami will be back next week with more original content.
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Surfing NASH returns to its regular program with a fresh episode and some fascinating and progressive ideas around non-invasive testing. Mazen Noureddin joins co-hosts Jörn Schattenberg, Louise Campbell and Roger Green to discuss serum identification of at-risk MASH and the Metabolomics-Advanced Steatohepatitis Fibrosis Score (MASEF). In late July, Mazen co-authored a paper on the subject which was published in Hepatology.
For this opening conversation, Mazen cogently introduces why and how MASEF came to exist as an emerging noninvasive test. He first notes the utility of the HbA1c test - one of the commonly used tests to diagnose prediabetes and diabetes and also the main test to assist health care teams manage diabetes - suggesting that hepatology could benefit from having something similar for risk stratification and disease identification. While not exactly comparable to having an HbA1c test for NAFLD, Mazen suggests this work with MASEF to be “a step in the right direction.” He then goes on to describe the research background and partnerships with an experienced metabolomics team before describing in further detail study parameters and notable findings. At the end of the session, Jörn inserts a question which clarifies the diversity of cohorts. Lastly, Mazen raises the idea that MASEF could be used alternatively to liver stiffness measurement by VCTE in the algorithm that is currently recommended by several guidance publications.
If you have questions or comments around MASEF, metabolomics or any other ideas considered in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com. The Surfing the NASH Tsunami will be back next week with more original content.
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This week, Surfing NASH returns to its regular program with a fresh episode and some fascinating and progressive ideas around non-invasive testing. Mazen Noureddin joins co-hosts Jörn Schattenberg, Louise Campbell and Roger Green to discuss serum identification of at-risk MASH and the Metabolomics-Advanced Steatohepatitis Fibrosis Score (MASEF). Mazen co-authored a paper on the subject which was published in Hepatology as recent as late July. In a nutshell, this episode elucidates on developing and validating a highly specific metabolomics-driven score to identify at-risk MASH (metabolic dysfunction-associated steatohepatitis) patients.
Ultimately, the paper concludes MASEF to indeed be a promising diagnostic tool for the assessment of at-risk MASH. Specifically, it states that MASEF "could be used alternatively to liver stiffness measurement by VCTE in the algorithm that is currently recommended by several guidance publications." Listen to the Surfers respond with their thoughts, questions and varying perspectives.
If you have questions or comments around MASEF, metabolomics or any other ideas considered in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com. The Surfing the NASH Tsunami will be back next week with more original content.
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Last week SurfingNASH offered a final re-focus on an episode that originally aired during Season 1. Continuing on the focus around allied health, this session dives into the role of nurses, physicians and allied health professionals in supporting NASH patients - a topic of increasing relevance as the field grapples with new nomenclature for liver disease and the imminence of therapeutic approvals. Specifically, the group explores whether healthcare systems can be as effective as companies like Noom and WeightWatchers.
This fascinating conversation features ideas shared by Stephen Harrison, Peter Traber (Chief Medical Officer at Selecta Biosciences ), Louise Campbell and Roger Green. Roger begins by framing the discussion around three questions:
1) For allied professionals how much of their focus lies in maintaining and enhancing wellness as compared to treating illness?
2) How do these two concepts differ both in the minds of professionals and in terms of what information and guidance they present to patients?
3) What are the keys in supporting patients' focus on wellness, both during the office visit and afterwards?
Louise responds based on her own experience as she recently moved out of the NHS to focus on more early stages of the disease, where it's ultimately easier to change behavior and encourage wellness and preventative practices in general. Louise connects the idea that liver patients tend not to get information until later in their disease to the announcement that the British government made on creating a far reaching policy around obesity and its likely impact on patient health. In response to one of the questions from Roger, Louise goes on to discuss how we present information in ways that empower patients to take better care of themselves. Done right, this can extend beyond the individual patients and to their families and other supporters. Peter agrees and comments based on his own past experiences in medical practice. He notes that patients have extensive care teams with multiple areas of expertise and patients are best served when the care team members actually act as a team (keeping in mind especially that 2020 was mid-pandemic).
If you have questions or comments around our From the Vault series, allied health, education or any other ideas addressed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com. The Surfing the NASH Tsunami will be back next week with more original content.
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This week SurfingNASH continues to offer a final re-focus on an episode that originally aired during Season 1. Similar to last week's focus on allied health, this session dives into the role of nurses, physicians and allied health professionals in supporting NASH patients - a topic of increasing relevance as the field grapples with new nomenclature for liver disease and the imminence of therapeutic approvals. Specifically, the group explores whether healthcare systems can be as effective as companies like Noom and WeightWatchers. The fascinating conversation features ideas and critical concepts shared by Stephen Harrison, Peter Traber (Chief Medical Officer at Selecta Biosciences ), Louise Campbell and Roger Green.
If you have questions or comments around our From the Vault series, allied health, education or any other ideas addressed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com. The Surfing the NASH Tsunami will be back next week with more original content.
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SurfingNASH is offering something different for Season 4, Episode 37 while the co-hosts are off enjoying a well-deserved holiday amid a busy year. Rather than leaving a gap in the podcast's program, this week we are revisiting an episode From the Vault that, now more than ever, maintains its relevance. As the field grapples with new nomenclature for liver disease and the imminence of therapeutic approvals, education and educational resources are critically needed. This session, led by Louise Campbell, focuses on the roles that allied health can play in prevention, early stage management and clinical trial recruitment for NAFLD/NASH. Allied health is our primary interface for the education and support within the clinical setting of patients with any disease. Allied health professionals are a vastly experienced resource supporting both physicians and patients in the delivery of care and efficacy. Stephen Harrison also joins Louise and guest panelists (Kathryn Jack, Michele Clayton, Pam O’Donoghue and Patrizia Kunzler) to consider the many ways that liver nurses and advanced nursing practitioners can do more to support NASH education and patient management and where they should fit into the paradigm. This conversation explores the need for and value of patient education in the NASH Patient Care process. It starts with almost a tangential request that some of the money budgeted for expensive systemic HCC therapies in the UK be rededicated to patient education earlier in the treatment process. From there, the conversation shifts to consider the value of the need for early-stage treatment strategies in poorer countries that are never likely to be able to afford the expense of drugs or treatment modalities. In the end, each panelist describes a change she would like to see in the next 2-3 years.
If you have questions or comments around our From the Vault series, allied health, education or any other ideas addressed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
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SurfingNASH is offering something different for Season 4, Episode 37 while the co-hosts are off enjoying a well-deserved holiday amid a busy year. Rather than leaving a gap in the podcast's program, this week we are revisiting an episode From the Vault that, now more than ever, maintains its relevance. As the field grapples with new nomenclature for liver disease and the imminence of therapeutic approvals, education and educational resources are critically needed. This session, led by Louise Campbell, focuses on the roles that allied health can play in prevention, early stage management and clinical trial recruitment for NAFLD/NASH. Allied health is our primary interface for the education and support within the clinical setting of patients with any disease. Allied health professionals are a vastly experienced resource supporting both physicians and patients in the delivery of care and efficacy. Stephen Harrison also joins Louise and guest panelists (Kathryn Jack, Michele Clayton, Pam O’Donoghue and Patrizia Kunzler) to consider the many ways that liver nurses and advanced nursing practitioners can do more to support NASH education and patient management and where they should fit into the paradigm. This conversation explores the different challenges that liver nurses and advanced practitioners face when providing NASH patient education. It starts with Stephen noting that this weeks’ reported results from Madrigal’s MAESTRO-NAFLD Phase 3 trial promises a day when we can reduce HCC and cirrhosis if we can counsel patients early enough in the process. From there, the conversation shifts to consider the different specialties that can play a role, including not only hepatologists and nurses but also podiatrists, bariatricians, endocrinologists, and gynecologists. The rest of the conversation covers an array of prospective educational tools and the need for specific education that hits specific key points.
If you have questions or comments around our From the Vault series, allied health, education or any other ideas addressed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
SurfingNASH is offering something different for Season 4, Episode 37 while the co-hosts are off enjoying a well-deserved holiday amid a busy year. Rather than leaving a gap in the podcast's program, this week we are revisiting an episode From the Vault that, now more than ever, maintains its relevance. As the field grapples with new nomenclature for liver disease and the imminence of therapeutic approvals, education and educational resources are critically needed. This session, led by Louise Campbell, focuses on the roles that allied health can play in prevention, early stage management and clinical trial recruitment for NAFLD/NASH. Allied health is our primary interface for the education and support within the clinical setting of patients with any disease. Allied health professionals are a vastly experienced resource supporting both physicians and patients in the delivery of care and efficacy. Stephen Harrison also joins Louise and guest panelists (Kathryn Jack, Michele Clayton, Pam O’Donoghue and Patrizia Kunzler) to consider the many ways that liver nurses and advanced nursing practitioners can do more to support NASH education and patient management and where they should fit into the paradigm. This conversation explores the different challenges that liver nurses and advanced practitioners face when providing NASH patient support. It focuses on issues including health discrimination, the general challenges in deploying nursing care early in the disease progression and the mismatch of needs and resources. In the end, we learn about nurses who make their own recordings and encourage patients to create their own discussion groups in the medical office.
If you have questions or comments around our From the Vault series, allied health, education or any other ideas addressed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
SurfingNASH is offering something different for Season 4, Episode 37 while the co-hosts are off enjoying a well-deserved holiday amid a busy year. Rather than leaving a gap in the podcast's program, this week we are revisiting an episode From the Vault that, now more than ever, maintains its relevance. As the field grapples with new nomenclature for liver disease and the imminence of therapeutic approvals, education and educational resources are critically needed. This session, led by Louise Campbell, focuses on the roles that allied health can play in prevention, early stage management and clinical trial recruitment for NAFLD/NASH. Allied health is our primary interface for the education and support within the clinical setting of patients with any disease. Allied health professionals are a vastly experienced resource supporting both physicians and patients in the delivery of care and efficacy. Stephen Harrison also joins Louise and guest panelists (Kathryn Jack, Michele Clayton, Pam O’Donoghue and Patrizia Kunzler) to consider the many ways that liver nurses and advanced nursing practitioners can do more to support NASH education and patient management and where they should fit into the paradigm. In this conversation, we meet the four key nursing opinion leaders who have joined Louise and Stephen and learn about the broad sets of skills and experiences each brings to the table. At the start of the episode, Stephen responds to a question that a patient e-mailed to SurfingNASH.com during the previous week.
If you have questions or comments around our From the Vault series, allied health, education or any other ideas addressed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
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SurfingNASH is offering something different for Season 4, Episode 37 while the co-hosts are off enjoying a well-deserved holiday amid a busy year. Rather than leaving a gap in the podcast's program, this week we are revisiting an episode From the Vault that, now more than ever, maintains its relevance. As the field grapples with new nomenclature for liver disease and the imminence of therapeutic approvals, education and educational resources are critically needed. This session, led by Louise Campbell, focuses on the roles that allied health can play in prevention, early stage management and clinical trial recruitment for NAFLD/NASH. Allied health is our primary interface for the education and support within the clinical setting of patients with any disease. Allied health are a vastly experienced resource supporting both physicians and patients in the delivery of care and efficacy. Stephen Harrison also joins Louise and guest panelists (Kathryn Jack, Michele Clayton, Pam O’Donoghue and Patrizia Kunzler) to consider the many ways that liver nurses and advanced nursing practitioners can do more to support NASH education and patient management and where they should fit into the paradigm. Listen on to learn more about how the Fatty Liver community can make the best use of these talented and knowledgeable resources.
If you have questions or comments around our From the Vault series, allied health, education or any other ideas addressed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
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One of the most important challenges facing Fatty Liver stakeholders involves improving early diagnosis for patients with clinically relevant or advanced fibrosis (F2/3). Today, a significant percentage of patients learn they are living with cirrhosis in the Emergency Department during a decompensating event. Four in ten of these patients in the UK do not leave the hospital. Episode 39 reviewed a model that Ian Rowe and Richard Parker developed to determine the most cost-effective strategy for F2/3 diagnosis.
This conversation From the Vault centers around challenges related to early diagnosis and NASH Patient Management. As Roger Green notes, listeners to NASH Tsunami might recall a significant number of conversations in which patients and advocates complain about doctors telling them “not to worry” about their Fatty Livers for years until the condition progresses to cirrhosis. Louise Campbell focuses on a different challenge: that of NASH patient management when patients are dealing with other metabolic diseases that are better known or where approved treatments exist.
Co-hosts Louise Campbell and Roger Green are joined by friend of the podcast, Naim Alkhouri, and new guest, Professor James O’Beirne, to discuss learning from liver disease in Australia and developing improved models for patient identification and risk stratification.
This final conversation starts with Roger discussing the idea that upscaling training is very important. Louise follows up with a comment that we must remember these are complicated technologies to use and that dedication to training is pivotal in optimizing their potential. After a digression to consider the size of the indigenous candidates in the study, the group moves onto a final question. James shares what comes next in the study and the other panelists comment on what can be taken away from this discussion in terms of improving screening or cost effectiveness.
If you have questions or comments around the LOCATE-NAFLD study or any other ideas addressed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
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Co-hosts Louise Campbell and Roger Green are joined by friend of the podcast, Naim Alkhouri, and new guest, Professor James O’Beirne, to discuss learning from liver disease in Australia and developing improved models for patient identification and risk stratification.
This conversation focuses largely on funding, starting with Louise’s question about Medicare payment for patients in Australia. James notes that all care was free to patients, and that this might skew results. As the conversation continues, Louise notes the importance for Australians of having Australian data to use in valuing medicines, diagnostics and procedures, given that NICE analyses rely exclusively on UK data. She goes on to ask about the quality of referrals from primary care, which prompts James to note that some primary care practitioners provided better data and novel referrals, while others appeared overwhelmed by the data. Roger asks the group how geographic dispersion will affect referrals as hepatologists push into primary care relationships. James suggests that geography is a challenge, leading Naim to comment that an inexpensive, hand-held device will be pivotal to mass screenings and that blood tests should be part of the mass screening armamentarium. James, followed by Louise, replies that nurses and some practitioners see imaging as a therapeutic event and an opportunity to engage the patient in a discussion of their numbers and how to improve lifestyles. As the conversation winds down, James and Naim discuss concerns around consistency of reads, and Louise, then Naim, provide tips on how to get a more accurate measurement.
If you have questions or comments around the LOCATE-NAFLD study or any other ideas addressed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
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Co-hosts Louise Campbell and Roger Green are joined by friend of the podcast, Naim Alkhouri, and new guest, Professor James O’Beirne, to discuss learning from liver disease in Australia and developing improved models for patient identification and risk stratification.
This conversation starts with Louise discussing some of the improvements in patient motivation and compliance as a result of FibroScan when administered in specialty sites. From here Roger asks Louise and James how they envision practical implementation of this kind of study design in other countries. Louise speculates on how this might work in 3rd world countries where there are large distances between communities and concludes it is quite feasible when dieticians and other allied professionals are empowered and can conduct scans. Naim discusses the extensive free-scan program that Arizona Liver Health offers which is typically focused on patients with type 2 diabetes, obesity and other risk factors. James notes that one element of the design is that it can provide cost analysis to demonstrate cost effectiveness and generate public funding in single-payer countries. Naim identifies limitations in the design and ways these might be ameliorated over time. As the conversation closes, James suggests that one cost saving might come from reducing treatment for patients who do not have high risk of disease.
If you have questions or comments around the LOCATE-NAFLD study or any other ideas addressed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
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Co-hosts Louise Campbell and Roger Green are joined by friend of the podcast, Naim Alkhouri, and new guest, Professor James O’Beirne, to discuss learning from liver disease in Australia and developing improved models for patient identification and risk stratification.
This conversation proceeds from a high-level overview of the LOCATE-NAFLD study. Discussion opens to comments from the panelists, starting with Naim commending the basic idea of a randomized study and the sample size for this initiative. He goes on to ruminate on how effective this design will be at correctly assessing positive and negative predictive values. James describes some of the funding and regulatory issues that shaped the design. As the conversation continues, it becomes clear that the median times to referral in the intervention and control groups were dramatically different and that these differences will have real clinical impact in a world with approved NASH agents. Louise raises the point that this kind of model can speed access to trial tremendously. James shares ideas around what motivated patients to enroll in the study and explains that significant numbers of patients screened out, most often due to high levels of alcohol consumption. As the conversation winds down, James mentions two interesting pieces of data from early analysis: a significant and clinically meaningful differences between successful FibroScan reads in the two groups and, separately, the lack of separation between the groups in quality of life scores.
If you have questions or comments around the LOCATE-NAFLD study or any other ideas addressed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
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Co-hosts Louise Campbell and Roger Green are joined by friend of the podcast, Naim Alkhouri, and new guest, Professor James O’Beirne, to discuss learning from liver disease in Australia and developing improved models for patient identification and risk stratification.
This conversation starts with an introduction to James both personally and professionally. A Consultant Hepatologist at the Sunshine Coast University Hospital, James describes how he came to his work and interests around risk stratification in liver disease, particularly in NAFLD, hepatocellular carcinoma and portal hypertension. From here Louise shares a bit about why she feels the LOCATE-NAFLD study is compelling and well-worth an investigation on the podcast. Among her notes, Louise praises the study for its integration and comparison of different pathways and outcomes. At the bottom of the session, James provides a high-level overview of the study:
RationaleNAFLD is the most common type of chronic liver disease in Australia. NAFLD is associated with a reduction in health-related quality of life, and as the number of NAFLD cases increase, the health system will incur increased costs associated with its diagnosis, management and disease progression. Currently, many patients who present to primary care with abnormal liver function tests or steatosis on liver ultrasound are referred for assessment in secondary care. Due to the large number of patients with NAFLD, this results in long waits for clinical and fibrosis assessment, placing unnecessary burden on the public hospital system. The study proposes to introduce better and faster assessment and stratification of patients in the community. As a result, the study aims to significantly reduce referrals for hospital-based appointments, and improve surveillance of high-risk disease, resulting in enhanced management of complications that result in avoidable, high cost admissions.
Study DesignThe LOCATE-NAFLD study is a 1:1 parallel randomized trial to compare two alternative models of care for NAFLD (usual care versus LOCATE-NAFLD).
Usual care group
- Patients will attend a specialist hepatology clinic for their care.
LOCATE-NAFLD group
- Patients will be assessed by a specialist study nurse in the primary care setting, such as local general practice clinic.
- The specialist nurse will assess patients using mobile transient elastography, using a FibroScan machine.
- Scan results will be reviewed by the specialist nurse and hepatologist
- Patients with low levels of liver scarring will be referred back to their GP for care
- Patients with high levels of liver scarring will be followed up in secondary care hepatology clinics
Quality of life will be assessed for all patients at baseline and at 12-month follow-up via a questionnaire. The study will analyse intervention costs, hospital outpatient clinic utilization, hospital admissions, hospital costs and patient death data.
If you have questions or comments around the LOCATE-NAFLD study or any other ideas addressed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
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Co-hosts Louise Campbell and Roger Green are joined by friend of the podcast, Naim Alkhouri, and new guest, Professor James O’Beirne, to discuss liver disease in Australia and developing improved models for patient identification and risk stratification.
James , a Consultant Hepatologist at the Sunshine Coast University Hospital, shares his professional background and introduces events which lead to the LOCATE-NAFLD study. After Australia became the first country to allow access to direct-acting antiviral agents for HCV in 2016, there was the strong need to determine which patients were cirrhotic. With relatively unprepared primary care providers, specialist and hospital care were inundated with referrals. In response, James contributed to the inception of a mobile FibroScan program to deliver scans, assessments and treatment recommendations to community health clinics and GP practices. The program was very successful and it was decided that data should be published followed by an economic analysis to demonstrate how this was an effective model of democratizing access to risk stratification. As it was later sought to be applied to different disease areas, the LOCATE-NAFLD project was born. James outlines the parameters which can be read in a succinct overview here:
The LOCATE-NAFLD study is a 1:1 parallel randomized trial to compare two alternative models of care for NAFLD (usual care versus LOCATE-NAFLD).
Usual care group
- Patients will attend a specialist hepatology clinic for their care.
LOCATE-NAFLD group
- Patients will be assessed by a specialist study nurse in the primary care setting, such as local general practice clinic.
- The specialist nurse will assess patients using mobile transient elastography, using a FibroScan machine.
- Scan results will be reviewed by the specialist nurse and hepatologist
- Patients with low levels of liver scarring will be referred back to their GP for care
- Patients with high levels of liver scarring will be followed up in secondary care hepatology clinics
Quality of life will be assessed for all patients at baseline and at 12-month follow-up via a questionnaire. The study will analyse intervention costs, hospital outpatient clinic utilization, hospital admissions, hospital costs and patient death data.
From here the conversation opens to comments from the other panelists and Naim commends that this effort is being studied in a randomized trial and goes on to ask questions around protocol. Louise discusses the impact conducting FibroScan has on mediating patient behavior and the potential reach this sort of model has as she considers empowering the likes of dieticians and other skilled practitioners. Roger introduces ideas around extrapolating these insights for use in countries outside of Australia and goes on to discuss clinical care pathways and what motivating frontline treaters looks like both in the absence and presence of approved medications. Naim shares his experiences venturing into Arizona with mobile FibroScan consultations, mostly focused on patients with type 2 diabetes, obesity and other risk factors. The second half of the conversation touches more on economic analysis and the impact of improving technology on delivering more consistent results for scans. For final question, Roger prods James for what's next in this story and asks Louise and Naim what about this conversation influences their work and respective locations today.
If you have questions or comments around the LOCATE-NAFLD study or any other ideas addressed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
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The wider community of liver stakeholders witnessed an exciting July as new compelling data and presentations were revealed across two major meetings, EASL Congress and the American Diabetes Association Scientific Sessions. Throughout that month, SurfingNASH provided real-time coverage and review of the emerging stories spanning topics like drug development, new nomenclature, omics and AI, NITs and more. For this episode the trio of co-hosts, Jörn Schattenberg, Louise Campbell and Roger Green, embark on their first exclusive discussion together in a while without any guest panelists. The overarching theme of the program observes what has made 2023 interesting and exciting thus far before offering a look into what the audience can expect to learn more about in the imminent months.
This conversation focuses largely on the episodes we have planned for the next couple of months. It starts with Louise discussing episodes she will be potentially leading in August while Jörn and then Roger go off on holiday. The group goes on to offer a glimpse into other items expected to be covered later in the year. If you want to learn more about what you can soon expect from this podcast, listen on.
Reviewing this episode and the various conversations is a strong reminder of how much information has already become available this year and what it portends in terms of future episodes and an ever-increasing explosion of new information about liver disease, drugs, testing, and so much more. If you have questions or comments around the EASL Congress or ADA meetings, the discussed therapeutics, new nomenclature, or any other topic addressed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
The wider community of liver stakeholders witnessed an exciting July as new compelling data and presentations were revealed across two major meetings, EASL Congress and the American Diabetes Association Scientific Sessions. Throughout that month, SurfingNASH provided real-time coverage and review of the emerging stories spanning topics like drug development, new nomenclature, omics and AI, NITs and more. For this episode the trio of co-hosts, Jörn Schattenberg, Louise Campbell and Roger Green, embark on their first exclusive discussion together in a while without any guest panelists. The overarching theme of the program observes what has made 2023 interesting and exciting thus far before offering a look into what the audience can expect to learn more about in the imminent months.
This conversation starts with continued focus around the new nomenclature, but moves on quickly from there to Louise's highlight of the year. She talks about how patients now play a larger role in all facets of education and drug development. Jörn agrees with this note and suggests that the level of patient involvement in this disease is far greater than what is observed elsewhere. Roger agrees with both statements, although expresses caveats about the need over time to move forward from simply including patient voices to actually listening to what they have to say and taking guidance from them with higher degree of success. From here, Roger introduces his highlight which is a combination of NIT development that will make these tests more pivotal on patient diagnosis management and, separately, new artificial intelligence modalities that utilize biopsy results to produce better pictures and a far more sophisticated level of disease understanding than we've had to date. Jörn and Louise both comment on issues they consider pivotal and highly valuable in terms of the use of NITs and lessons from AI.
Reviewing this episode and the various conversations is a strong reminder of how much information has already become available this year and what it portends in terms of future episodes and an ever-increasing explosion of new information about liver disease, drugs, testing, and so much more. If you have questions or comments around the EASL Congress or ADA meetings, the discussed therapeutics, new nomenclature, or any other topic addressed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
The wider community of liver stakeholders witnessed an exciting July as new compelling data and presentations were revealed across two major meetings, EASL Congress and the American Diabetes Association Scientific Sessions. Throughout that month, SurfingNASH provided real-time coverage and review of the emerging stories spanning topics like drug development, new nomenclature, omics and AI, NITs and more. For this episode the trio of co-hosts, Jörn Schattenberg, Louise Campbell and Roger Green, embark on their first exclusive discussion together in a while without any guest panelists. The overarching theme of the program observes what has made 2023 interesting and exciting thus far before offering a look into what the audience can expect to learn more about in the imminent months.
This conversation focuses significant attention on issues related to the change in nomenclature that was rolled out in final form at the recent EASL Congress in June. It starts with Roger sharing an item from a recent news story about Madrigal Pharmaceuticals deciding not to engage in the nomenclature change until regulatory agencies ruled on it - a logical step given where resmetirom stands in the approval process. Roger comments that while the name change is necessary, there are some challenges in terms of communicating the disease. Louise notes how important communicating disease properly is in educating patients and expresses concern that professionals might not communicate the disease (or communicate it properly) if there is confusion around nomenclature as there currently appears to be. Jörn asserts that we're not confused about the disease that patients have, but only how to describe it. Roger suggests that while he is not concerned about hepatologists communicating new nomenclature, he does have concerns around the ease and clarity by which primary care and nursing professionals who populate the frontline will be prepared to deliver this new information. Jörn and Louise agree with this take and Jörn states that we need to shift focus towards looking at how to educate the frontline treat categories if we are to succeed with this nomenclature and the work that needs to be done for this disease.
Reviewing this episode and the various conversations is a strong reminder of how much information has already become available this year and what it portends in terms of future episodes and an ever-increasing explosion of new information about liver disease, drugs, testing, and so much more. If you have questions or comments around the EASL Congress or ADA meetings, the discussed therapeutics, new nomenclature, or any other topic addressed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
The wider community of liver stakeholders witnessed an exciting July as new compelling data and presentations were revealed across two major meetings, EASL Congress and the American Diabetes Association Scientific Sessions. Throughout that month, SurfingNASH provided real-time coverage and review of the emerging stories spanning topics like drug development, new nomenclature, omics and AI, NITs and more. For this episode the trio of co-hosts, Jörn Schattenberg, Louise Campbell and Roger Green, embark on their first exclusive discussion together in a while without any guest panelists. The overarching theme of the program observes what has made 2023 interesting and exciting thus far before offering a look into what the audience can expect to learn more about in the imminent months.
This conversation begins with Louise detailing a paper that she recently co-authored on 'The Accuracy of Ultrasound Controlled Attenuation Parameter (CAP) in Diagnosing Hepatic Fat Content.' The aim of this study was to delineate the accuracy of CAP in diagnosing hepatic steatosis, compared to the gold standard of liver biopsy. Notes on the topic broaden to consider the value of elastography and the challenges of making proper use of it. From here, the group shares comments around how the major events and conferences have panned out so far for 2023. Jörn notes that while the volume of information available grows over time, a clear set of events which captures attention relates to the advancement of resmetirom as a potential first approval for NASH-directed therapy. He recounts the trajectory of this story beginning in December 2022 with a press release of positive Phase 3 topline results, to follow up data presented at EASL Congress 2023 in June. Jörn highlights his excitement for analyzing these results on the podcast with Stephen Harrison, Principle Investigator of the MAESTRO studies. Briefly, Jörn underscores the second key event of the year: new nomenclature for liver diseases. When his comments around this conclude, the trio spend the rest of this conversation discussing the importance behind a resmetirom approval and some of the interesting data that emerged from later releases of the MAESTRO trials.
Reviewing this episode and the various conversations is a strong reminder of how much information has already become available this year and what it portends in terms of future episodes and an ever-increasing explosion of new information about liver disease, drugs, testing, and so much more. If you have questions or comments around the EASL Congress or ADA meetings, the discussed therapeutics, new nomenclature, or any other topic addressed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
The wider community of liver stakeholders witnessed an exciting July as new compelling data and presentations were revealed across two major meetings, EASL Congress and the American Diabetes Association Scientific Sessions. Throughout that month, SurfingNASH provided real-time coverage and review of the emerging stories spanning topics like drug development, new nomenclature, omics and AI, NITs and more. For this episode the trio of co-hosts, Jörn Schattenberg, Louise Campbell and Roger Green, embark on their first exclusive discussion together in a while without any guest panelists. The overarching theme of the program observes what has made 2023 interesting and exciting thus far before offering a look into what the audience can expect to learn more about in the imminent months.
Louise starts by detailing a paper that she recently co-authored on 'The Accuracy of Ultrasound Controlled Attenuation Parameter (CAP) in Diagnosing Hepatic Fat Content.' The aim of this study was to delineate the accuracy of CAP in diagnosing hepatic steatosis, compared to the gold standard of liver biopsy. From here, Jörn shares his take on the biggest stories of the year thus far. He begins by recounting the December 2022 press release of positive Phase 3 topline results for resmetirom and describes how the data was presented at EASL Congress 2023. Jörn highlights his excitement for analyzing these results on the podcast with Stephen Harrison, Principle Investigator of the MAESTRO studies. Secondly, Jörn underscores the adoption of new nomenclature as an obvious hallmark of the year.
Roger notes several developments in the resmetirom story following the EASL presentation, namely around a submission to FDA and potential timeline for approval. Louise suggests that, "from the patient advocacy perspective, there has to be something approved shortly to prove that the path that the FDA has set is actually achievable." The group also explores the importance behind having quality of life measures as opposed to solely targeting histological improvement of fibrosis. These ideas lead Roger to register his interest in developing understanding around the role of inflammation which has been explored more recently on the podcast.
The conversation shifts to consider the new nomenclature and what activities are required in its successful implementation. Several important ideas emerge around education and moving forward collectively in continued pursuit of promoting liver health and saving lives. Jörn summarizes that fundamentally the patients and the disease remain the same and that there is actionable knowledge around how to prevent, diagnose and treat. As the session winds down, the trio focus on providing a glimpse into what's coming up for the SurfingNASH program. Listen on to learn more about what you can expect to hear from the Surfers!
If you have questions or comments around the EASL Congress or ADA meetings, the discussed therapeutics, new nomenclature, or any other topic addressed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
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Last year, Stephen Harrison expounded on a string of press releases presaging some of the most promising data of the last decade in NASH drug development. As Principal Investigator, he reviewed on the podcast Phase 2b results from Akero’s HARMONY Trial. This is a 24-week study evaluating the efficacy and safety of the FGF-21 agonist efruxifermin (EFX) in patients with clinically relevant NASH (F2-F3). The study met its primary endpoint for both the 50mg and 28mg EFX dose groups. Respectively, 41% and 39% of EFX-treated patients experienced at least a one-stage improvement in liver fibrosis with no worsening of NASH by week 24 (compared with 20% for the placebo arm).
Stephen walks through his presentation on Akero’s lead product candidate EFX and two important points emerge. First, Stephen and Sven Francque share the idea that “not all FGF-21’s are created equal.” FGF-21’s themselves need to be stabilized due to their two-hour half-lives. The first FGF-21, pegbelfermin, was PEGylated and revealed significant challenges in clinical development. EFX is a bivalent structure – two molecules stabilized by a fusion protein. This appears to work far better. The conversation continues with more points and questions about the study results and implications. An interesting idea surfaces: EFX might function better as an induction therapy to be followed by an oral maintenance therapy and a long-term monotherapeutic solution. As the session winds down, the group speculate the dynamics of what happens when disease regresses to a point where there is far less liver damage.
This month, Surfing NASH embarks on a series of episodes dedicated to takeaways emerging from June's two major conferences: the 2023 EASL Congress in Vienna and the American Diabetes Association's 83rd Scientific Sessions meeting in San Diego. In doing so, the Big Band of Surfers (Stephen Harrison, Jörn Schattenberg, Louise Campbell and Roger Green) are joined by Mazen Noureddin for a fascinating conversation which covers compelling data and ideas emerging from the drug development space.
This final conversation covers a range of topics. Jörn starts off with comments around the importance of safety as well as some thoughts about dosing strategy relative to safety and initial tolerability. Stephen picks up on this issue before moving on to consider whether the drugs discussed have an impact on cravings for alcohol and might be successful in a broader set of patients. He then goes on to identify two concerns for the agent class: suicidal ideation and possible amounts of lean muscle loss, both of which need to be for further. Jörn notes that lean muscle loss might be particularly critical in the study of patients with cirrhosis who are frail to begin with. Stephen continues by discussing a review of the frequency of lean muscle loss for GLP-1s, suggesting a 20 to 50% loss in many cases. Finally, Louise comments on the possible psychological effects of this weight loss. All this leads to Roger's final question which asks what have we learned in the last month that might affect research or conceptual thinking going forward? The topics each panelists chooses vary largely, but the concepts and all the thoughts around them are stimulating and worth a listen.Each conversation covers a lot of ground on drug development, analysis of trial results, and the upcoming increases in importance of omics and artificial intelligence.If you have questions or comments around the EASL Congress or ADA meetings, or the themes and data discussed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On
This month, Surfing NASH embarks on a series of episodes dedicated to takeaways emerging from June's two major conferences: the 2023 EASL Congress in Vienna and the American Diabetes Association's 83rd Scientific Sessions meeting in San Diego. In doing so, the Big Band of Surfers (Stephen Harrison, Jörn Schattenberg, Louise Campbell and Roger Green) are joined by Mazen Noureddin for a fascinating conversation which covers compelling data and ideas emerging from the drug development space.
This episode starts with a welcome (and happy birthday) to Roger as he belatedly joins the discussion. From here Mazen discusses some of the implications of the anticipated upcoming approval for resmetirom and what that will mean for treatment, drug development and noninvasive tests. Stephen nexts dives into the phase 2b pemvidutide trial in greater detail. In response, Jörn notes that the weight loss is not what you might have expected from a GLP-1 and asks whether this has to be a function of GLP-1 to glucagon ratio. Stephen notes that there is a relatively high level of glucagon to GLP-1 in pemvidutide that might translate not only into greater antifibrotic activity, but also possibly a lower level of side effects relative to a combination agent with a lower level of glucagon compared to GLP-1.
Each conversation covers a lot of ground on drug development, analysis of trial results, and the upcoming increases in importance of omics and artificial intelligence.If you have questions or comments around the EASL Congress or ADA meetings, or the themes and data discussed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On
This month, Surfing NASH embarks on a series of episodes dedicated to takeaways emerging from June's two major conferences: the 2023 EASL Congress in Vienna and the American Diabetes Association's 83rd Scientific Sessions meeting in San Diego. In doing so, the Big Band of Surfers (Stephen Harrison, Jörn Schattenberg, Louise Campbell and Roger Green) are joined by Mazen Noureddin for a fascinating conversation which covers compelling data and ideas emerging from the drug development space.
Mazen starts this conversation by stressing the importance of omics, particularly metabolomics and proteomics, in creating a single blood-based measure that can offer standardization around evaluation or, otherwise, a small set of standard tests. He goes on to describe breakthrough obesity presentations at the ADA meeting and returns to the question that he raised in Episode 31: do we need NASH drugs given how powerful the upcoming weight-loss pharmacotherapies will be? He simply says, yes we do, and describes why. Stephen returns to the topic of omics, stating his preference for additional omics works, albeit with some skepticism about proteomics. That said, he questions whether omics will get a far enough and expresses hope that epigenetics might get even further. The rest of this conversation entails Mazen, Stephen and Jörn discussing biomarkers and omics issues. Stephen wraps up the session by noting that we will have plenty to talk about in this arena for years to come. Finally, he mentions AI as another key area for future growth.
Each conversation covers a lot of ground on drug development, analysis of trial results, and the upcoming increases in importance of omics and artificial intelligence.If you have questions or comments around the EASL Congress or ADA meetings, or the themes and data discussed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On
This month, Surfing NASH embarks on a series of episodes dedicated to takeaways emerging from June's two major conferences: the 2023 EASL Congress in Vienna and the American Diabetes Association's 83rd Scientific Sessions meeting in San Diego. In doing so, the Big Band of Surfers (Stephen Harrison, Jörn Schattenberg, Louise Campbell and Roger Green) are joined by Mazen Noureddin for a fascinating conversation which covers compelling data and ideas emerging from the drug development space.
Jörn and Mazen begin by prompting Stephen with questions around the FASCINATE-2 study outlined in the previous conversation. Stephen confirms that the data presented was based on a planned interim analysis of a prespecified subset of patients at week 26 of a 52-week trial. Mazen next asks questions designed to challenge Stephen to reveal how excited he truly is about the drug (denifanstat) and surrounding data. Specifically, Mazen asks whether denifanstat feels like an add-on agent when compared to more 'mainstream' FGF-21 agents. Stephen responds by referring to a need for what he characterizes as a plethora of agents before commenting on possible and practical differences between orals and injectables. He suggests that injectables seem to produce faster drops in liver fat reduction and ALT improvements than orals, although orals may 'catch up' over time in a sort of 'tortoise and the hare' phenomenon. From here Stephen describes the ways which he might use injectables first in more severe patients before introducing orals after achieving the desired effect. He also talks about simply starting with orals in less severe patients. The group digs deeper into these ideas by introducing ACC inhibitors and pan-PPAR agonist, lanifibranor, to the conversation. Finally, concluding comments return to the theme that injectables might produce stronger efficacy results, although there are several agents yet to be clearly differentiated among orals.
Each conversation covers a lot of ground on drug development, analysis of trial results, and the upcoming increases in importance of omics and artificial intelligence.If you have questions or comments around the EASL Congress or ADA meetings, or the themes and data discussed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On
This month, Surfing NASH embarks on a series of episodes dedicated to takeaways emerging from June's two major conferences: the 2023 EASL Congress in Vienna and the American Diabetes Association's 83rd Scientific Sessions meeting in San Diego. This is the second session focusing on drug development, and specifically, on several presentations for exciting drugs in development. In doing so, the Big Band of Surfers (Stephen Harrison, Jörn Schattenberg, Louise Campbell and Roger Green) are joined by Mazen Noureddin for a fascinating conversation which covers plenty of compelling clinical trial data.
Jörn preludes this discussion by noting just how much important drug development research was released at this year's EASL Congress. Stephen proceeds from here to detail positive Phase 2b FASCINATE-2 clinical trial interim data for fatty acid synthase (FASN) inhibitor, denifanstat, as presented at EASL Congress by Rohit Loomba. In the process, Stephen elucidates why the idea of a FASN inhibitor is so exciting. It blocks de novo lipogenesis, which means it can have effects on inflammation and possibly direct fibrosis inhibition. Previously in Season 4, Episode 32, it was discussed why inflammation, which is tied to liver volume, might be a critical component to better understand for therapuetic development and the wider scope of liver health. From here, Stephen goes on to describe the trial, starting with basic design and sharing the MRI-PDFF and biomarker data that was presented at the EASL Congress. He finishes with safety and efficacy data and a general comment that the trial demonstrated, 'the drug is doing what it's intended.'
The following excerpt is from the Sagiment Biosciences press release on this topic:
The Phase 2b FASCINATE-2 study is a 52-week randomized, double-blind, placebo-controlled trial evaluating the safety and histological impact of a 50mg daily oral dose of denifanstat compared to placebo in 168 biopsy-confirmed NASH patients with moderate-to-severe fibrosis (stage F2 or F3). The primary efficacy endpoint is histological (liver biopsy) improvement at week 52 in nonalcoholic fatty liver disease (NAFLD) activity score (NAS) without worsening of fibrosis or resolution of steatohepatitis without worsening of fibrosis. Secondary endpoints include biomarkers of inflammation, fibrosis and liver injury.
- Denifanstat was well-tolerated and met primary endpoint in planned interim readout with 67% of treated patients achieving ≥30% reductions in liver fat at week 26 compared to 18% placebo (p<0.001) as assessed by MRI-PDFF
- Denifanstat statistically significantly decreased LDL cholesterol in treated patients and improvements in the circulating blood lipid profile were observed
- Topline week 52 liver biopsy results expected in the first quarter of 2024
Each conversation covers a lot of ground on drug development, analysis of trial results, and the upcoming increases in importance of omics and artificial intelligence.If you have questions or comments around the EASL Congress or ADA meetings, or the themes and data discussed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On
This month, Surfing NASH embarks on a series of episodes dedicated to takeaways emerging from June's two major conferences: the 2023 EASL Congress in Vienna and the American Diabetes Association's 83rd Scientific Sessions meeting in San Diego. This is the second session focusing on drug development, and specifically, on several presentations for exciting drugs in development.
This session kicks off with a twist as co-host Jörn Schattenberg introduces the episode and its panelists because Roger Green is late (he will join later with a bit of birthday banter). Joining this in-depth discussion around the latest drug development stories to emerge from the EASL and ADA meetings is Stephen Harrison, Mazen Noureddin and Louise Campbell.
Stephen starts the episode by discussing findings from the Phase 2b FASCINATE trial of the FASN inhibitor denifanstat, as presented at the EASL Congress by Rohit Loomba. After describing key efficacy and safety findings, Stephen notes that denifanstat does pretty much what observers expected it to do. Mazen follows up with a series of questions noting that denifanstat's efficacy does not appear equal to the FGF-21s efruxifermin and pegozafermin, and asks whether it will become a "front-line" or "add-on" agent. In response, Stephen suggests we will need a plethora of modes of action, that orals and injectables will each have a place depending on the type of patient, and that this will compete for front-line use in less severe patients and maintenance use in more severe patients with the other oral agent classes. From here, the conversation moves on to discuss the increasing importance of omics and epigenetics, and the role these may play in the future.
This is the point at which Roger joins the discussion. Because Mazen has to leave, Roger asks him a broad question about markers for the future; Mazen bases his answer on the anticipated future approval of resmetirom. After he leaves, Stephen presents results from the Phase 2b study for the dual GLP-1/glucagon agonist pemvidutide, which wanders into the importance of the actual GLP-1-to-glucagon impact ratio, potentially significant safety signals that remain to be fully studied, and the subject of how much lean muscle mass these agents produce. This leads Louise Campbell into a brief but fascinating comment on the psychological impacts of lean muscle mass on different patients.
In the final question, Roger asks the group what we have learned in the previous month that might affect research design or disease strategy thinking going forward. The answers vary widely, and each has value.
If you have questions or comments around the EASL Congress or ADA meetings, the discussed therapeutics, new nomenclature, or any other topic addressed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
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The first three days of the 2022 program focused on a range of issues, with specific emphasis on non-invasive tests (NITs) and their role at different stages in diagnosis and treatment. This conversation From the Vault touches on two issues: use of AI to better understand the meaning of liver volume and elements of morphology and, relatedly, how much more sophisticated a view we take of NAFLD and NASH than we did even five years ago.
The issues around AI and liver morphology arise from Jörn Schattenberg’s comment that consistent with Stephen Harrison’s “KISS” (Keep It Simple, Stupid!) principle, researchers are starting to explore the meaning of changes in liver volume. Ultimately, Jörn notes, pairing these kinds of measures to AI-supported histopathology can yield tremendous benefits. Roger comments on a breakfast he attended that morning that suggested that AI and NITs each provide different, important information on individual liver health: NITs can address collagen burden but not structure, while AI can identify changes in structure but not link them to the impact on the patient. Zobair ends this part of the conversation by noting that companies are starting to use AI in these ways.
The second part of this conversation stems from Roger’s observation that we know far more about the disease than we did 3-4 years ago. He goes on to describe how the environment is more collaborative and open-minded than it might have been if, in fact, we saw drug approvals at that time. Zobair takes this observation to a different plane, noting that 5-10 years ago, “some very important experts” believed that we all understood the etiology of Fatty Liver disease, so why spend more time? He goes on, “we could not have been more wrong,” observing that what we have learned about progression and regression in placebo arms suggests a far more complex disease than something that progresses linearly, or even constantly in one direction. He goes on to add that the multiple drug trial failures is that targeting drugs to a single solution based on animal models is likely to fail because this is a multiple mode of action disease. His third point: the “source” of the disease is visceral obesity and insulin resistance, which all viable solutions must address. This identifies two targets for treatment, while simultaneously demonstrating that therapy will be chronic, lifelong and with behavioral elements. The rest of the conversation addresses the challenges with shaping this kind of lifelong, multi-target therapy in the US today.
Throughout the month of July, Surfing NASH embarks on a series of episodes dedicated to takeaways emerging from a busy past month at both the 2023 EASL Congress and the American Diabetes Association's 83rd Scientific Sessions. For this feature, Sven Francque (University of Antwerp) and Ian Rowe (University of Leeds) join Jörn Schattenberg and Roger Green to discuss a range of fascinating topics to emerge at the EASL Congress meeting held in Vienna.
This final conversation begins with Sven's choice to discuss another paper by Vincent Wong that correlated liver stiffness with risk of decompensation and HCC. It is noted that the study relied on repetitive MRE readings over time and could not be performed in many different countries. This leads to comments around the plausibility of shifting from biopsy to NITs and insights around the cost effectiveness and the frequency of testing. On the flip side, Ian next underscores a study that investigates identification of a gene signature that will accurately predict the risk of decompensationand, ultimately, determine how to make better use of the biopsy tissue received in research. Finally, the session winds down with a closing question around what to expect in next year's meeting.
If you have questions or comments around the EASL Congress meeting, new nomenclature, discussed papers or any other ideas addressed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
Throughout the month of July, Surfing NASH embarks on a series of episodes dedicated to takeaways emerging from a busy past month at both the 2023 EASL Congress and the American Diabetes Association's 83rd Scientific Sessions. For this feature, Sven Francque (University of Antwerp) and Ian Rowe (University of Leeds) join Jörn Schattenberg and Roger Green to discuss a range of fascinating topics to emerge at the EASL Congress meeting held in Vienna.
This conversation begins with Roger's note of a population study from South Korea looking to identify patients with steatotic liver disease, but not cirrhosis, that will progress to HCC over a ten year period. After sharing the study details, both Ian and Jörn express common concern around the relatively small size of the identified patient group. Jörn shares his hope that with new disease classification which combines metabolic and alcoholic components we will be able to study these issues more broadly in populations that might be more finely tuned for the study aims. Next, Jörn highlights a paper that leads the group to unpack how little is known about the mechanisms of fibrosis resolution beyond the idea that there are clear differences between the progression and regression processes.
If you have questions or comments around the EASL Congress meeting, new nomenclature, discussed papers or any other topics addressed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
Throughout the month of July, Surfing NASH embarks on a series of episodes dedicated to takeaways emerging from a busy past month at both the 2023 EASL Congress and the American Diabetes Association's 83rd Scientific Sessions. For this feature, Sven Francque (University of Antwerp) and Ian Rowe (University of Leeds) join Jörn Schattenberg and Roger Green to discuss posters and presentations that they find critical and/or compelling.
Ian starts this conversation by pointing to unmet needs in the primary care setting for disease identification. He refers to a related presentation of interest from Vincent Wong titled A clinical care pathway to detect advanced liver disease in patients with type 2 diabetes through automated fibrosis score calculation and electronic reminder messages: a randomised controlled trial. Ian suggests that this study proves both the value of working to identify more patients and the considerable amount of work remaining in this area. The group goes on to discuss what the implications of this study are for treatment in primary care both now and into the future of patient care. In particular, Jörn elucidates the value of FIB-4 not only as a screening tool for liver-related outcomes, but also as a predictor of cardiovascular risk and all-cause mortality. Secondly, Jörn notes that when a NASH therapy becomes available, "the granularity of picking up those patients will be higher" and physicians will be more motivated to take action provided that they have both a screening tool and available treatment to prescribe. This leads to discussion around the differences between hepatology and private medicine practices and management of a population-level disease. Ian raises the question around how frequent should testing be performed in the primary care setting for different pathways.
If you have questions or comments around the EASL Congress meeting, new nomenclature, discussed papers or any other topics addressed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
Throughout the month of July, Surfing NASH embarks on a series of episodes dedicated to takeaways emerging from a busy past month at both the 2023 EASL Congress and the American Diabetes Association's 83rd Scientific Sessions. For this feature, Sven Francque (University of Antwerp) and Ian Rowe (University of Leeds) join Jörn Schattenberg and Roger Green to discuss a range of fascinating topics to emerge at the EASL Congress meeting held in Vienna.
This conversation focuses on the outcome of the nomenclature process, a three-stage Delphi process that produced new names and classification for what had previously been known as fatty liver disease and henceforth will be known as the steatotic liver disease (SLD). Sven, who was actively involved in the entire exercise, gives a concise summary of the process by which the new classifications were developed and how the new terminology will work. The rest of the conversation focuses on three issues. First, excitement that we will now have the opportunity to study patients whose disease has both metabolic and alcohol-based components. Second, the processes by which the three clinicians, Sven, Ian and Jörn are starting to share the new structure with their patients with varying degrees of success. One interesting observation emerges here from Sven: the English language terms do not translate equally into Dutch, so there is a patient advocate-led effort to create a new set of terms in Dutch. Third, Roger raises concerns about implementation planning for the new nomenclature. One concern is around the possible impact on drug or diagnostic development and the other about the kinds of communication issues covered earlier episodes. Sven, who again worked more closely on the process, states with confidence that the change will not have impact on drug or diagnostic trials. Read more about the switch to steatotic liver disease (SLD) and metabolic dysfunction-associated steatotic liver disease (MASLD) here.
If you have questions or comments around the EASL Congress meeting, new nomenclature, discussed papers or any other topics addressed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
Throughout the month of July, Surfing NASH embarks on a series of episodes dedicated to takeaways emerging from a busy past month at both the 2023 EASL Congress and the American Diabetes Association's 83rd Scientific Sessions. For this feature, Sven Francque (University of Antwerp) and Ian Rowe (University of Leeds) join Jörn Schattenberg and Roger Green to discuss a range of fascinating topics to emerge at the EASL Congress meeting held in Vienna.
The episode begins on the subject of new NAFLD/NASH nomenclature. Sven provides a cogent summary of the background, processes and decisions related to the name changes. The other panelists respond with varying perspectives and expand on the following ideas that emerge:
- the changes reflect an opportunity to study metabolically at-risk populations that consume more than little-to-no alcohol
- the adoption of more neutral scientific terms - steatotic rather than fatty -destigmatizes the condition
- In general, improved clarity around definition of disease is a positive step forward in putting a major dent in the pandemic
The conversation shifts to practical considerations around how to implement the changes in different settings and with patients. Read more about the switch to steatotic liver disease (SLD) and metabolic dysfunction-associated steatotic liver disease (MASLD) here.
The group refocuses on posters and presentations that they find critical and/or compelling. Ian points to a presentation from Vincent Wong titled A clinical care pathway to detect advanced liver disease in patients with type 2 diabetes through automated fibrosis score calculation and electronic reminder messages: a randomised controlled trial. Ian suggests that this study proves both the value of working to identify more patients and the considerable amount of work remaining in this area. Roger next mentions a population study from South Korea looking to identify patients with steatotic liver disease, but not cirrhosis, that will progress to HCC over a ten year period. After the group comments on this study, Jörn highlights a paper which unpacks how little is known about the mechanisms of fibrosis resolution beyond the idea that there are clear differences between the progression and regression processes. Sven then chooses to discuss another paper by Vincent Wong that correlated liver stiffness with risk of decompensation and HCC. This leads to comments around the plausibility of shifting from biopsy to NITs and insights around the cost effectiveness and the frequency of testing. On the flip side, Ian underscores a study that investigates identification of a gene signature that will accurately predict the risk of decompensationand, ultimately, determine how to make better use of the biopsy tissue received in research. Finally, the session winds down with a closing question around what to expect in next year's meeting.
If you have questions or comments around the EASL Congress meeting, new nomenclature, discussed papers or any other ideas addressed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
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In 2022, roughly 5,000 liver community stakeholders gathered in London for the 2022 International Liver Congress (#ILC2022,) the first major hepatology Congress to be held in person since the start of the pandemic (smaller, but very valuable, meetings like NASH-TAG, LiverCONNECT and Paris NASH have taken place with an in-person component, but the International Liver Congress and The Liver Meeting have not). On the last full day of the program, several vitally important drug development studies were presented during the late-breaker and dedicated sessions.
This particular conversation From the Vault focuses on the semaglutide cirrhosis late-breaker and, more broadly, what panelists consider the presentation from this Congress most likely to effect change over the next 2-3 years.
Because Stephen Harrison needs to depart, the episode starts with him answering a question about the most consequential paper in the Congress. He focuses on the resmetirom late-breaker, which presages potential drug approval within the next 18 months. Jörn Schattenberg takes a different tack, identifying the semaglutide cirrhosis late-breaker instead. Jörn notes that the study did not achieve its primary endpoint of 1-level fibrosis reduction in 48 weeks, but cites other studies and experiences to suggest this is very, very hard to achieve for any drug. Jörn continued to suggest that semaglutide’s safety level combined with ability to help patients lose weight and reduce their HbA1c levels means this can be a valuable drug for Fatty Liver patients as well as diabetics and people with obesity, the currently indicated patient populations. From here, the group provides answers to the “most consequential presentation” question and the conversation comes to an end.
If you have questions or comments around the topics addressed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
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Throughout the month of July, Surfing NASH embarks on a series of episodes dedicated to takeaways emerging from a busy past month at both the 2023 EASL Congress in Vienna and the American Diabetes Association's 83rd Scientific Sessions meeting in San Diego. To reflect on the insight-laden occasion, Stephen Harrison and Jörn Schattenberg join Roger Green to explore emerging drug development stories in detail.
This conversation starts with a discussion about the importance of treating early stage cirrhosis patients. Jörn suggests that with new agents in place we may soon be looking to treat other patient populations such as, for example, those with HCC. In such instances NASH drugs will become adjuvant therapy to improve treatment against the primary disease target. Stephen agrees, noting that we will need a better test to diagnose HCC and, once available, there will be fewer presentations of advanced HCC because we will have treated more of them earlier with better agents and adjuvant therapies. Again, all this will await the approval of NASH and ideally cirrhosis drugs in the future. Roger asks how to identify the 20 to 30% of HCC patients who develop cancer before NASH. Stephen suggests it depends largely on NIT development. From there the panelists each share final thoughts around what the session has yet to cover that is important. Stephen comes up with a new idiom and Jörn speculates a new concept. Listen to the session to find out what they are.
If you have questions or comments around the EASL Congress or ADA meetings, the discussed therapeutics, new nomenclature, or any other topic addressed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
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Throughout the month of July, Surfing NASH embarks on a series of episodes dedicated to takeaways emerging from a busy past month at both the 2023 EASL Congress in Vienna and the American Diabetes Association's 83rd Scientific Sessions meeting in San Diego. To reflect on the insight-laden occasion, Stephen Harrison and Jörn Schattenberg join Roger Green to explore emerging drug development stories in detail.
In this session, conversation shifts from resmetirom to Mazen Noureddin's "NASH Monopoly" game and focus on the value of FGF-21s and glucagon agents. Stephen posits two comments about GLP-1s. First, there is now adequate data suggesting that GLP-1s will not melt away all liver fat and as a result lead to dramatic fibrosis regression. Second, we know from a small sub-cohort of patients in Akero's SYMMETRY trial that patients already on fairly low doses of GLP-1s saw what Stephen describes as an 'incredible' and incremental benefit for the FGF-21 agent, efruxifermin. The group notes that while glucagon dual and treble agents are likely to produce dramatically more robust results in weight loss and liver defatting than GLP-1s alone, they still seem unlikely to 'usurp the need for other types of agents.' From here discussion considers the FGF-21 class. Stephen notes that two drugs, efruxifermin and pegozafermin, have demonstrated significant efficacy against fibrosis. As the conversation concludes, the panelists agree that earlier, more aggressive screening to arrest cirrhosis will become pivotal and will not occur until the right drug becomes available.If you have questions or comments around the EASL Congress or ADA meetings, the discussed therapeutics, new nomenclature, or any other topic addressed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
Throughout the month of July, Surfing NASH embarks on a series of episodes dedicated to takeaways emerging from a busy past month at both the 2023 EASL Congress in Vienna and the American Diabetes Association's 83rd Scientific Sessions meeting in San Diego. To reflect on the insight-laden occasion, Stephen Harrison and Jörn Schattenberg join Roger Green to explore emerging drug development stories in detail.
This conversation continues on data presented by Stephen on the MAESTRO series of trials for resmetirom. It starts with a few clarifications on data presented in regards to liver volume. This discussion point evolves to consider how liver volume is not well understood and the three speculate what sort of useful insights can be derived from bridging that gap in knowledge. Stephen steers discussion back to the specific data by discussing the resmetirom safety profile. First, he shares the practical implications of safety for these drugs in everyday use. Next he provides an encouraging safety profile for the trial. As he does so, he shares thoughts about how to and how not to interpret a diahrea metric. Jörn responds by stating that the safety and liver volume profile suggest a reduction in liver pain and associated improvements to quality of life. He suggests the latter might be important with European regulators. As the conversation winds down, Stephen expresses his hope that the rolling submission with possible priority review and this profile will produce extremely positive news within the next 6 to 8 months.If you have questions or comments around the EASL Congress or ADA meetings, the discussed therapeutics, new nomenclature, or any other topic addressed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
Throughout the month of July, Surfing NASH embarks on a series of episodes dedicated to takeaways emerging from a busy past month at both the 2023 EASL Congress in Vienna and the American Diabetes Association's 83rd Scientific Sessions meeting in San Diego. To reflect on the insight-laden occasion, Stephen Harrison and Jörn Schattenberg join Roger Green to explore emerging drug development stories in detail.
This conversation focuses largely on therapeutic candidate, resmetirom, and a series of MAESTRO-NASH trials that will hopefully lead to a first drug approval and treatment for NASH. Stephen, lead Principal Investigator of the MAESTRO program, begins by outlining the resmetirom clinical trial package in its entirety. Before Stephen shares numbers from the trial, Jörn opens a discussion around efficacy endpoints. He notes the structure of reading biopsy and suggests that reporting improvement in fibrosis and NASH resolution might not accurately reflect the extent of efficacy once the MAESTRO outcomes trial completes several years from now and patients are treated in practice. Stephen goes on to share the efficacy outcomes of the MAESTRO-NASH trial and offers notes from several different perspectives around dosing, placebo, metrics and other elements of the study population. Finally, Stephen suggests where in the liver he believes the drug works and why the drug might have more robust effects than can currently be measured using the testing tools available.
If you have questions or comments around the EASL Congress or ADA meetings, the discussed therapeutics, new nomenclature, or any other topic addressed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
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Throughout the month of July, Surfing NASH embarks on a series of episodes dedicated to takeaways emerging from a busy past month at both the 2023 EASL Congress in Vienna and the American Diabetes Association's 83rd Scientific Sessions meeting in San Diego. For this feature, Stephen Harrison and Jörn Schattenberg discuss at depth drug development insights emerging from the meetings with host Roger Green.
As lead Principle Investigator, Stephen expounds on Phase 3 MAESTRO-NASH data on resmetirom that he presented during the opening general session. He begins with a cogent backdrop of the study parameters, including endpoint criteria, before detailing results and implications. In his analysis, Stephen notes the challenges of teasing how well a drug performs in comparison to placebo. He then expands on the power of AI in digital pathology and its ability to enhance assessment of biopsy beyond ordinal scoring systems. Jörn adds that these extension studies are fascinating for their ability to hone in on patient benefits experienced beyond liver histology alone. From here, the group discusses at length deepening the field's understanding of liver volume reduction.
Moving on, Roger revisits a metaphor from Mazen Noureddin in last week's episode which likened the two most valuable properties in "NASH Monopoly" to GLP-1s and FGF-21s. Stephen suggests a takeaway to be that "GLP's are coming to the forefront as a very active player in the fields of obesity, diabetes and ultimately CV risk reduction." The group next agrees that, in Jörn's paraphrased words, while a defatting effect on the liver can be beneficial, treating obesity by itself does not outright resolve fibrogenic burden and there remains the need for more liver-directed drugs. Stephen expands on his recurring phrase of "not all FGF-21s are created equal" while transitioning the group's focus to consider the fact that an increasing number of patients are progressing to cirrhosis. The remainder of the conversation posits fascinating and far-reaching speculations on the future study of disease including revolutionizing the way we diagnose HCC. In final comments, each panelist touches on one additional element in the drug development landscape to emerge out of an exciting month of June.
If you have questions or comments around the EASL Congress or ADA meetings, the discussed therapeutics, new nomenclature, or any other topic addressed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
Throughout the month of July, Surfing NASH embarks on a series of episodes dedicated to takeaways emerging from a busy last few weeks at both the 2023 EASL Congress in Vienna and the American Diabetes Association's 83rd Scientific Sessions meeting in San Diego. This first installment comprises two distinct 1:1 interviews with Tsunami co-host Roger Green, one with key opinion leader Mazen Noureddin and the other with co-host Jörn Schattenberg.
This final conversation between Roger and Jörn begins by moving beyond the subject of drugs to the importance behind noninvasive testing and the myriad ways by which the term artificial intelligence is being claimed. Jörn talks about a poster he shared at EASL around an AI-assisted mode called qVessel which investigates the ability of researchers to quantitate changes in blood vessels and liver architecture as fibrosis progresses.This example provides contrast between how we develop diagnostic scientific insight versus drug approval process versus clinical applications and patient treatment. The conversation continues on to highlight some of what Jörn and Roger consider to be some of the most exciting drug development pieces to emerge from the EASL and ADA meetings. This leads to comments around how the nature of the questions being asking in 2023 versus 2019 demonstrates how much the field has learned about liver disease over the last few years. Our entire key opinion leader and advocate team has been struck forcibly by how many studies in the last month provided significant advances in knowledge and how some of these advances may change an underlying appreciation of drugs, diagnostics, artificial intelligence, machine learning and how we think about Fatty Liver disease overall.
Both conversations with Mazen and Jörn explore different perspectives around the complexities associated with drug development and the wider field's understanding of Steatotic Liver Disease (SLD). Stay tuned for more in the subsequent conversations to be released. If you have any questions or comments around these meetings, the discussed therapeutics or the new nomenclature, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
Throughout the month of July, Surfing NASH embarks on a series of episodes dedicated to takeaways emerging from a busy last few weeks at both the 2023 EASL Congress in Vienna and the American Diabetes Association's 83rd Scientific Sessions meeting in San Diego. This first installment comprises two distinct 1:1 interviews with Tsunami co-host Roger Green, one with key opinion leader Mazen Noureddin and the other with co-host Jörn Schattenberg.
This first conversation with Jörn starts with discussion around the idea that even dramatic improvements in obesity medications will not resolve all issues related to fibrosis in MASLD patients. After speculation around the therapeutic landscape for NASH, conversation turns toward the new nomenclature consensus and what this will mean for the liver community and beyond.
Both conversations with Mazen and Jörn explore different perspectives around the complexities associated with drug development and the wider field's understanding of Steatotic Liver Disease (SLD). Stay tuned for more in the subsequent conversations to be released. If you have any questions or comments around these meetings, the discussed therapeutics or the new nomenclature, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
Throughout the month of July, Surfing NASH embarks on a series of episodes dedicated to takeaways emerging from a busy last few weeks at both the 2023 EASL Congress in Vienna and the American Diabetes Association's 83rd Scientific Sessions meeting in San Diego. This first installment comprises two distinct 1:1 interviews with Tsunami co-host Roger Green, one with key opinion leader Mazen Noureddin and the other with co-host Jörn Schattenberg.
This second and final conversation with Mazen continues to explorewhat we do or do not know about the different mechanisms of action in NASH drugs and the commercial implications. Later, the Monopoly metaphor around NASH therapeutic development as described in the preceding conversation is expanded. Roger shares his interesting idea on how Big Pharma is similar to the role of Hollywood in movie production and distribution opportunities. Finally, the two discuss why it is critical to move beyond ordinal histopathology reads in the drug approval process before sharing final thoughts around what factors are contributing to an exciting future for combating liver disease.
Both conversations with Mazen and Jörn explore different perspectives around the complexities associated with drug development and the wider field's understanding of Steatotic Liver Disease (SLD). Stay tuned for more in the subsequent conversations to be released. If you have any questions or comments around these meetings, the discussed therapeutics or the new nomenclature, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
Throughout the month of July, Surfing NASH embarks on a series of episodes dedicated to takeaways emerging from a busy last few weeks at both the 2023 EASL Congress in Vienna and the American Diabetes Association's 83rd Scientific Sessions meeting in San Diego. This first installment comprises two distinct 1:1 interviews with Tsunami co-host Roger Green, one with key opinion leader Mazen Noureddin and the other with co-host Jörn Schattenberg.
This first conversation with Mazen begins with comments on the many excellent drug development studies emerging from both EASL Congress and the ADA's Scientific Sessions meeting. While the two share exceptional results, they also explore potential downsides in terms of tolerability and longterm antibody inflammation. An illustrative new metaphor is coined by Mazen in which the NASH therapeutic landscape is likened to the game Monopoly. In "NASH Monopoly," each street or monopoly presents a mechanisms of action. The two most expensive streets to GLP-1s and FGF-21s. He goes on to commend and describe the promise of GLP-1s and the double and triple agents in development as leading to such significant weight loss that some question the need for bariatric procedures altogether.
Both conversations with Mazen and Jörn explore different perspectives around the complexities associated with drug development and the wider field's understanding of Steatotic Liver Disease (SLD). Stay tuned for more in the subsequent conversations to be released. If you have any questions or comments around these meetings, the discussed therapeutics or the new nomenclature, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
Surfing NASH embarks on a series of episodes dedicated to takeaways emerging from a busy last few weeks at both the 2023 EASL Congress in Vienna and the American Diabetes Association's 83rd Scientific Sessions meeting in San Diego. In this first instalment comprising two distinct interviews, host Roger Green takes a deep dive into insights with two leading Key Opinion Leaders, Mazen Noureddin and Jörn Schattenberg.
The first conversation with Mazen begins with an illustrative new metaphor in which the NASH therapeutic landscape is likened to the game Monopoly. For example, if Mazen were to place multiple mechanisms of action on different streets, he says that he would assign the two most expensive streets to GLP-1s and FGF-21s. He goes on to commend and describe the promise of GLP-1s and having orals that lead to such significant weight loss as to call to question the need for bariatric procedures altogether. From here the two discuss in detail how GLP-1s are to become more accessible and what the future may hold for this drug class.
In the sequential segment featuring Jörn, Roger continues to press on pertinent issues surrounding drug development. Jörn's first note underscores growing points of intersection between different fields concerned with managing metabolic dysfunction and how different toolkits might make positive impact on liver health. Roger switches the metaphor of Monopoly to a new description of the developing therapeutic landscape akin to a desert where mirages present as promising drugs and "any drink of water is as good as any other drink." As conversation continues, Jörn and Roger expound on the subject of new nomenclature and what this will mean for different stakeholders.
The two conversations with Mazen and Jörn explore different perspectives around the complexities associated with drug development and the wider field's understanding of Steotic Liver Disease (SLD). If you have any questions or comments around these meetings, the discussed therapeutics or the new nomenclature, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
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Surfing NASH delivered a second wrap-up session on-site in Vienna as a part of its real-time coverage of a truly thought-provoking EASL Congress 2023. This conversation held after the Saturday late breakers features key opinion leaders Hannes Hagström and Michelle Long, entrepreneur and epigenetics advocate Rachel Zayas and patient advocates Jeff McIntyre and Michael Betel alongside host Roger Green.
This conversation covers a few interesting moments from the conference, starting with the appearance of Tetiana Deshko to speak about the gruesome realities of public health care in Ukraine during the invasion. From there, Jeff talks about a broader issue of how we support funding of treatments in parts of the world that lack hepatologists or adequate resources. The group also discusses the idea that Predictive Health Intelligence in the UK has begun to improve patient screening dramatically with a simple, non AI-based data analysis methodology that could likely be applied in a variety of regions. Michael comments on the session where the question arose whether physicians should inform patients about having fatty liver disease before drug therapies were available to treat it. Spoiler alert: the patient advocate answer is an emphatic yes! Finally, Roger's closing question asks the group about what they learned in the meeting that will change their work going forward.
For a variety of reasons, EASL Congress 2023 has been looked forward to by the liver community with arguably an unprecedented sense of excitement and intensity. The conversations resulting from the podcast’s two real-time reviews suggest that the actual event met or exceeded such high expectations. If you have any question or interests around EASL Congress, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
Surfing NASH delivered a second wrap-up session on-site in Vienna as a part of its real-time coverage of a truly thought-provoking EASL Congress 2023. This conversation held after the Saturday late breakers features key opinion leaders Hannes Hagström and Michelle Long, entrepreneur and epigenetics advocate Rachel Zayas and patient advocates Jeff McIntyre and Michael Betel alongside host Roger Green.
This conversation starts with Roger asking each panelist to mention a poster or presentation that was particularly compelling or valuable. As befits the group, the panelist ultimately chose a wide range of topics. This includes thoughts around ways in which to evaluate NITs and deciding who and when to treat, data on the FGF-21 agent pegozafermin, the impact of RNA defects on disease and treatment and much more. As the conversation winds down, Roger suggests that there can be confusions around articifical intelligence (AI) as a term as it is applied to a myriad of technologies.
For a variety of reasons, EASL Congress 2023 has been looked forward to by the liver community with arguably an unprecedented sense of excitement and intensity. The conversations resulting from the podcast’s two real-time reviews suggest that the actual event met or exceeded such high expectations. If you have any question or interests around EASL Congress, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
Surfing NASH delivered a second wrap-up session on-site in Vienna as a part of its real-time coverage of a truly thought-provoking EASL Congress 2023. This conversation held after the Saturday late breakers features key opinion leaders Hannes Hagström and Michelle Long, entrepreneur and epigenetics advocate Rachel Zayas and patient advocates Jeff McIntyre and Michael Betel alongside host Roger Green. The discussion picks up on the topic of the announced MAESTRO-NASH Phase 3 results and the panelists' various reactions. This subject quickly beckons questions around the scoring systems used to evaluate NASH and specifically some shortcomings within the NASH CRN system. The group also anticipates the role that resmetirom will play in both the short and long term and the implications of superior patient support in both arms of the randomized clinical trials and how well the drug will be perceived to work in the treating community.
For a variety of reasons, EASL Congress 2023 has been looked forward to by the liver community with arguably an unprecedented sense of excitement and intensity. The conversations resulting from the podcast’s two real-time reviews suggest that the actual event met or exceeded such high expectations. If you have any question or interests around EASL Congress, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
Surfing NASH delivered an additional wrap-up session on-site in Vienna as a part of its real-time coverage of a truly thought-provoking EASL Congress 2023. This is the first of four conversations held after the Saturday late breakers with key opinion leaders Hannes Hagström and Michelle Long, entrepreneur and epigenetics advocate Rachel Zayas and patient advocates Jeff McIntyre and Michael Betel. Roger Green asks each panelist to share a word or short phrase that captures their feelings about the event. The answers from this session differ from those in response to the same question in the preceding episode 29, even from both Michael and Roger who are a part of both sessions. From here the group goes on to explore some implications of the new nomenclature rollout that occurred that morning.
For a variety of reasons, EASL Congress 2023 has been looked forward to by the liver community with arguably an unprecedented sense of excitement and intensity. The conversations resulting from the podcast’s two real-time reviews suggest that the actual event met or exceeded such high expectations. If you have any question or interests around EASL Congress, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
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Surfing NASH offered on-site coverage of EASL Congress 2023 in two separate real-time reviews. This conversation features the final session exploring the first three days of the meeting with Ian Rowe, Michael Betel, Jörn Schattenberg and Roger Green. The focus of the group ranges from discussion around the FGF-21 agents efruxifermin and pegozafermin to the results of two major screening trials emerging from respected NAIL-NIT data. Finally, they discuss the broad rubric of AI and the many widely varying technologies that are currently described as utlizing AI. Roger’s closing question calls attention to a few additional major impressions from the event yet to be elaborated on in the preceding conversations. The panelist responses ranged from comments around the state of public health on Ukrainian frontlines, a different take on the NAIL-NIT presentation and lastly interest in the American Diabetes Association meeting taking place simultaneously in San Diego.
For a variety of reasons the entire community looks forward to this meeting with an unprecedented sense of intensity and excitement. These seven conversations suggest that the actual event met or exceeded such high expectations - listen on to learn how and why and stay tuned for Part 2 of this exclusive coverage. If you have any question or interests around EASL Congress, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
Surfing NASH offered on-site coverage of EASL Congress 2023 in two separate real-time reviews. This conversation continues from the first session featuring Ian Rowe, Michael Betel, Jörn Schattenberg and Roger Green and their focus on the first three days of the meeting. The group begins by discussing the Friday afternoon session that Jörn co-chaired which investigates the challenges in screening patients for fatty liver diseases. One issue that surfaces is the dynamic tension around time that frontline treaters in the UK grapple with between conducting multi-stage sequential screening and supporting behavioral interventions adequately. It is suggested that they are concerned with not being able to deliver on both of these critical aims without compromise. The conversation shifts to focus on the Friday morning session on therapies which were described as the second wave of NASH drugs. This includes discussion around two dual agonists, efinopegdutide and pemvidutide, that could achieve what Ian describes as "huge reductions" in liver fat. The group goes on to touch on two other presentations from that session, one covering the impact of intermittent fasting on the liver versus standard calorie reduction, the other on reporting results on an RNA-based product.
For a variety of reasons the entire community looks forward to this meeting with an unprecedented sense of intensity and excitement. These seven conversations suggest that the actual event met or exceeded such high expectations - listen on to learn how and why and stay tuned for Part 2 of this exclusive coverage. If you have any question or interests around EASL Congress, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
Surfing NASH offered on-site coverage of EASL Congress 2023 in two separate real-time reviews. This conversation comes from the first session featuring Ian Rowe, Michael Betel, Jörn Schattenberg and Roger Green. Roger begins by asking each panelist to share a word or short phrase that captured their impressions of the conference thus far. With varying adjectives, the group describes and elaborates how the meeting unfolds from their perspectives. From here they go on to discuss the impact of the opening General Session on Thursday and focus on Stephen Harrison’s presentation of the highly anticipated MAESTRO-NASH Phase 3 results.
For a variety of reasons, EASL Congress 2023 has been looked forward to by the liver community with arguably an unprecedented sense of excitement and intensity. The conversations resulting from the podcast’s two real-time reviews suggest that the actual event met or exceeded such high expectations. If you have any question or interests around EASL Congress, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
Surfing NASH delivers another wrap-up session on-site in Vienna in a real-time review of a truly thought-provoking EASL Congress 2023. The conversation features impressions of Hannes Hagström, Michelle Long, Rachel Zayas, Jeff McIntyre, Michael Betel and Roger Green in a discussion focused on a range of topics covered at the meeting. Notably, the group touches on the highly anticipated nomenclature announcement, fascinating basic scientific and therapeutic insights and much more.
Listen on to learn more and stay tuned for a Part 2 of this exclusive coverage. If you have any question or interests around the event, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!This episode was generously sponsored by Madrigal Pharmaceuticals.Madrigal Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company pursuing novel therapeutics for nonalcoholic steatohepatitis (NASH), a liver disease with high unmet medical need. Madrigal’s lead candidate, resmetirom, is a once daily, oral, thyroid hormone receptor (THR)-β selective agonist designed to target key underlying causes of NASH in the liver. For more information, visit www.madrigalpharma.com.
Surfing NASH delivers a session on-site in Vienna to offer a real-time review as EASL Congress 2023 unfolds. This first of two on-site recordings features Ian Rowe, Michael Betel, Jörn Schattenberg and Roger Green as the group digests takeaways from an energized meeting. Some topics they touch on include Madrigal's MAESTRO-NASH clinical trial of resmetirom, notes around interesting emerging liver science, the potential role of AI assistance, the NASH therapeutic landscape and many more milestones witnessed by the field since the days of Hep-C.
Listen on to learn more and stay tuned for a Part 2 of this exclusive coverage. If you have any question or interests around the event, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
For the first time in the 198-episode history of this podcast, Surfing NASH will not be hosting a discussion centered around NAFLD, NASH, steatotic liver disease or anything else connected to our title. Instead, we are sharing an incredibly moving story told at EASL Congress 2023 about the provision of health care in the war zones of Ukraine.
Roger Green had the opportunity at a press briefing to hear from Tetiana Deshko, Director of Programs for the Alliance for Public Health in Ukraine. Dr. Deshko shared her own experience with the challenges of providing health for patients in the midst of an invasion, particularly in occupied and battleground areas.
Think of this episode as a dramatically expanded weekly business report, in which Roger discusses the situation in Ukraine. That discussion is general, political and aspirational. The conversation featured here on Season 4, Epsiode 28 with Ms. Deshko is more specific and focused on the realities that treaters in Ukraine face each day. Her description is powerful and provokes emotions that words cannot describe. You can support her vital public health work by making donation to the Alliance for Public Health, one of the largest non-governmental organizations in Ukraine, (click this link to donate and read more about their important work).
This weekend Surfing NASH will resume its onsite coverage of EASL Congress 2023 with episodes dedicated to the outcome of the nomenclature process, late breakers and more. Stay tuned for more details. The world’s largest liver meeting takes place 21-24 June in Vienna with an international faculty of experts from over 200 institutions. The diverse program will feature 2500 abstracts and be a uniquely momentous occasion for developing multidisciplinary approaches aimed at putting a major dent in Fatty Liver disease.
If you have any question or interests around the event or Ms. Deshko's experiences in Ukraine, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On! Перемагаймо разом!
Surfing NASH serves yet another preview of a highly anticipated and upcoming EASL Congress in Vienna, this time focusing on a strong lineup of fascinating abstracts and engaging sessions. This final conversation comes in the form of a topical extra-sode which fits seamlessly into ongoing coverage of the event. Surfing NASH partnered with HistoIndex to produce a deep dive session into AI and pathology with Arun Sanyal and David Kleiner. This is high-caliber, stimulating discussion will improve your nuanced understanding of the challenges in using ordinal manual histopathology in NASH clinical trials and how AI systems might ameliorate or minimize these challenges.
The purpose of the episode is to establish a backdrop for an episode later this year when a major clinical trial investigating these issues will be released. The conversation starts with an important and telling digression. Roger asks David, Senior Researcher at the National Cancer Institute and chief pathologist of the NASH CRN, how working on NASH compares to earlier diseases like hepatitis C. David explains that disease and drug-related effects are far more complex in NASH than in hepatitis. He reasons that where hepatitis, a far more stable disease, only looks at fibrosis, NASH additionally considers steatosis and ballooning. Arun notes three benefits of AI: it can stabilize and standardize reads from the sample, it can provide information about the history of disease that a one time manual read cannot and it allows the researcher to layer in molecular and other tools to drive a far deeper understanding of underlying pathology. From here, the conversation hones into the benefits of AI assistance, including the value of improving measurement by creating continuous variable scoring, observation through multiple dimensions to determine what matters most and generally developing a richer, more nuanced understanding of liver health and disease.
Today’s episode is sponsored by HistoIndex, the first global company to provide stain-free, fully automated imaging solutions for visualizing and quantifying morphological and architectural features of fibrosis. HistoIndex couples breakthrough biophotonic technology with an AI-powered digital pathology system to provide consistent, high-throughput imaging in liver disease and cancer. The platform benefits clinical research and speeds development of drugs and diagnostics. For more information, visit www.histoindex.com.
Stay Safe and Surf On!
Surfing NASH extends its preview coverage of the upcoming EASL Congress with a three-part episode. This final conversation with Louise Campbell observes a paper she finds relevant to the recent NICE publishing of guidance around use of FibroScan in the primary care setting as well as International #NASHDay 2023. The presentation in reference is titled Patients with persistently abnormal liver biochemistry are under-investigated and can be rapidly identified using a novel case-finding database. Particularly, Louise notes that the paper is coming from the team of former podcast guest, Tim Jobson of Predictive Health Intelligence. The importance of being able to locate patients is underscored as critical in efforts to scan those with highest risk in the UK.
The world’s largest liver meeting takes place 21-24 June in Vienna with an international faculty of experts from over 200 institutions. The diverse program will feature 2500 abstracts and be a uniquely momentous occasion for developing multidisciplinary approaches aimed at putting a major dent in Fatty Liver disease. Stay tuned for more coverage and if you have any question or interests around the event, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Today’s episode is sponsored by HistoIndex, the first global company to provide stain-free, fully automated imaging solutions for visualizing and quantifying morphological and architectural features of fibrosis. HistoIndex couples breakthrough biophotonic technology with an AI-powered digital pathology system to provide consistent, high-throughput imaging in liver disease and cancer. The platform benefits clinical research and speeds development of drugs and diagnostics. For more information, visit www.histoindex.com.
Stay Safe and Surf On!
Surfing NASH extends its preview coverage of the upcoming EASL Congress with a three-part episode. This conversation continues on the theme of sessions and presentations of interest as anticipated by Louise Campbell alongside Roger Green. Louise begins by noting a poster on the causes of death in patients with NAFLD who presented on a spectrum of fibrosis stages at diagnosis. She goes on to note some fascinating conclusions of the study to tease links between liver disease and cardiovascular and extrahepatic cancer outcomes. Ultimately, Louise suggests that the evidence emerging strengthens her views on the need for stratifying NAFLD according to metabolic cardiovascular risk.
From here Louise points to a presentation by friend of the podcast Cyrielle Caussy titled Systematic screening for NAFLD-related advanced fibrosis in high-risk population in diabetology using transient elastography: a prospective study. The second leg of this conversation focuses on the paper and its implications for effective use of FIB-4 and developing our understanding of segmenting patient populations.
The world’s largest liver meeting takes place 21-24 June in Vienna with an international faculty of experts from over 200 institutions. The diverse program will feature 2500 abstracts and be a uniquely momentous occasion for developing multidisciplinary approaches aimed at putting a major dent in Fatty Liver disease. Stay tuned for more coverage and if you have any question or interests around the event, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Today’s episode is sponsored by HistoIndex, the first global company to provide stain-free, fully automated imaging solutions for visualizing and quantifying morphological and architectural features of fibrosis. HistoIndex couples breakthrough biophotonic technology with an AI-powered digital pathology system to provide consistent, high-throughput imaging in liver disease and cancer. The platform benefits clinical research and speeds development of drugs and diagnostics. For more information, visit www.histoindex.com.
Stay Safe and Surf On!
Surfing NASH extends its preview coverage of the upcoming EASL Congress with a three-part episode. This conversation comes from our final segment with Ian Rowe, Jörn Schattenberg and Roger Green. Jörn leads with thoughts around the Abstract session - NAFLD: Clinical Aspects. The session will touch on aspects that are, as Jörn puts it, “very close to what we're thinking today when we see patients.” He notes that topics covered around tools available now for treating and management will be of interest and utility for those seeing NASH patients. The group goes on to unpack this session before exploring presentations around pathology and developing understanding of disease staging, lean NAFLD, the role of miRNA, mitigating screening challenges and more. Jörn expresses excitement around his presentation of a poster as part of a cluster of NAIL-NIT data to emerge.
The world’s largest liver meeting takes place 21-24 June in Vienna with an international faculty of experts from over 200 institutions. The diverse program will feature 2500 abstracts and be a uniquely momentous occasion for developing multidisciplinary approaches aimed at putting a major dent in Fatty Liver disease. Stay tuned for more coverage and if you have any question or interests around the event, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Today’s episode is sponsored by HistoIndex, the first global company to provide stain-free, fully automated imaging solutions for visualizing and quantifying morphological and architectural features of fibrosis. HistoIndex couples breakthrough biophotonic technology with an AI-powered digital pathology system to provide consistent, high-throughput imaging in liver disease and cancer. The platform benefits clinical research and speeds development of drugs and diagnostics. For more information, visit www.histoindex.com.
Stay Safe and Surf On!
Surfing NASH extends its preview coverage of the upcoming EASL Congress with a three-part episode. This conversation continues to unpack the 2023 program with Ian Rowe, Jörn Schattenberg and Roger Green. Jörn begins by pointing to the Abstract session - NAFLD: Therapy which commences at 8:30 CEST on Friday morning. Specifically, he goes on to more closely detail a presentation related to time-restrictive eating which spurs an anecdote from Roger. Following, Ian describes what he finds fascinating about the opening presentation of this session concerning a Phase 2a, randomized, active-comparator-controlled, open-label study to evaluate the efficacy and safety of efinopegdutide in individuals with nonalcoholic fatty liver disease. This leads the group to comment on the influence of dual agonists in the wider landscape of drug development. The rest of the conversation considers the latest of what Roger presages to be a “fascinating set of advances” in the context of emerging individualized therapies by way of miRNA coupled with CAR-T to target fibrosis. In closing, Ian makes a point around “the amount of work that's going to be required if and when a drug is licensed.” Listen on to hear his thoughts.
The world’s largest liver meeting takes place 21-24 June in Vienna with an international faculty of experts from over 200 institutions. The diverse program will feature 2500 abstracts and be a uniquely momentous occasion for developing multidisciplinary approaches aimed at putting a major dent in Fatty Liver disease. Stay tuned for more coverage and if you have any question or interests around the event, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Today’s episode is sponsored by HistoIndex, the first global company to provide stain-free, fully automated imaging solutions for visualizing and quantifying morphological and architectural features of fibrosis. HistoIndex couples breakthrough biophotonic technology with an AI-powered digital pathology system to provide consistent, high-throughput imaging in liver disease and cancer. The platform benefits clinical research and speeds development of drugs and diagnostics. For more information, visit www.histoindex.com.
Stay Safe and Surf On!
Surfing NASH extends its preview coverage of the upcoming EASL Congress with a three-part episode. First up, Ian Rowe and Jörn Schattenberg speak to Roger Green about anticipations around the 2023 program and which abstracts are eye-catching and why. This conversation comes from that session and begins with Ian’s selection of a highly-anticipated abstract which will detail data from the MAESTRO-NASH clinical trial of resmetirom for the treatment of NASH and liver fibrosis. Specifically, Ian looks to learn more about the potential prevention of progression of fibrosis. Jörn adds the note that this abstract will be the first oral presentation to set the stage for the wider meeting. After a few more comments around expectations for the MAESTRO-NASH presentation, Jörn goes on to highlight interest in a poster being presented by a colleague titled, Impairment of health-related quality of life among people with type 2 diabetes and advanced fibrosis. Jörn describes that this is “not rocket science, but an application on how we do medicine these days for patients with NASH.” After a few additional notes on the topic, the baton is passed to Roger to discuss his interests around an oral poster titled Analytical and clinical validation of AIM-NASH: a digital pathology tool for artificial intelligence-based measurement of nonalcoholic steatohepatitis histology.Roger prefaces his enthusiasm for the paper with the note that Stephen Harrison has recently suggested on the podcast that FDA might accept AIM as a replacement for histology in terms of drug development. It’s Roger’s hunch that this may be a pivotal paper in that discussion and bring us closer to the idea of moving beyond histopathology to AI-assisted - or even AI-driven - reads for admission or endpoint assessment studies.
As the conversation winds down, Ian comments on his interest in developing an understanding around “how frequently tests need to be done and what magnitude of change in a biomarker predicts an outcome that is worse or indeed better.” This leads Jörn and Roger to tease what may be discussed in a session on diagnostics that will feature three seperate presentations by friends of the podcast Stephen Harrison, Naim Alkhouri and Mazen Noureddin.
The world’s largest liver meeting takes place 21-24 June in Vienna with an international faculty of experts from over 200 institutions. The diverse program will feature 2500 abstracts and be a uniquely momentous occasion for developing multidisciplinary approaches aimed at putting a major dent in Fatty Liver disease. Stay tuned for more coverage and if you have any question or interests around the event, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Today’s episode is sponsored by HistoIndex, the first global company to provide stain-free, fully automated imaging solutions for visualizing and quantifying morphological and architectural features of fibrosis. HistoIndex couples breakthrough biophotonic technology with an AI-powered digital pathology system to provide consistent, high-throughput imaging in liver disease and cancer. The platform benefits clinical research and speeds development of drugs and diagnostics. For more information, visit www.histoindex.com.
Stay Safe and Surf On!
Surfing NASH serves yet another preview of a highly anticipated and upcoming EASL Congress in Vienna, this time focusing on a lineup of heavy-hitting abstracts. This episode is split into three digestible sections. First up, Louise Campbell speaks to Roger Green about anticipations around the program and which abstracts are eye-catching and why. Next, Ian Rowe and Jörn Schattenberg join Roger to address a similar set of questions from their unique perspectives. Finally, the podcast has partnered with HistoIndex to produce a topical extra-sode around AI and pathology with Arun Sanyal and David Kleiner. This is an information-packed session with something for everyone, so sit back and enjoy the discussion.
The world’s largest liver meeting takes place 21-24 June in Vienna with an international faculty of experts from over 200 institutions. The diverse program will feature 2500 abstracts and be a uniquely momentous occasion for developing multidisciplinary approaches aimed at putting a major dent in Fatty Liver disease. Stay tuned for more coverage and if you have any question or interests around the event, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Today’s episode is sponsored by HistoIndex, the first global company to provide stain-free, fully automated imaging solutions for visualizing and quantifying morphological and architectural features of fibrosis. HistoIndex couples breakthrough biophotonic technology with an AI-powered digital pathology system to provide consistent, high-throughput imaging in liver disease and cancer. The platform benefits clinical research and speeds development of drugs and diagnostics. For more information, visit www.histoindex.com.
Stay Safe and Surf On!
In a monumental moment for combatting Fatty Liver disease, NICE has published the much anticipated evidence-based recommendations on FibroScan for assessing liver fibrosis and cirrhosis outside secondary and specialist care. Such a positive announcement comes at no better time than the start of the Surfing NASH ongoing coverage of International #NASHDay 2023 . To kick off the occasion, this first episode features hepatology researcher and KOL, William Alazawi, and new guest Vanessa Hebditch who serves as Director of Communications and Policy at the British Liver Trust. The panelists, alongside Louise Campbell and Roger Green, celebrate and comment on the new guidance on FibroScan use in the UK.
This final conversation starts with Roger's closing question: if this group reconvenes in 18 months, how will the UK have progressed on this frontier? The answers vary but mostly center on issues of screening, issues of care and issues of data and analysis.If you have questions or interest around NICE and FibroScan use, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
In a monumental moment for combatting Fatty Liver disease, NICE has published the much anticipated evidence-based recommendations on FibroScan for assessing liver fibrosis and cirrhosis outside secondary and specialist care. Such a positive announcement comes at no better time than the start of the Surfing NASH ongoing coverage of International #NASHDay 2023 . To kick off the occasion, this first episode features hepatology researcher and KOL, William Alazawi, and new guest Vanessa Hebditch who serves as Director of Communications and Policy at the British Liver Trust. The panelists, alongside Louise Campbell and Roger Green, celebrate and comment on the new guidance on FibroScan use in the UK.
In this session, each panelist offers their own take on where the devil is in the details can be applied to this subject. be themed. Much of the discussion comprises a fascinating interplay of ideas between Will and Louise about the best ways to implement community screening and more broadly, chronic disease management within the NHS system. Listen on to find out more.
If you have questions or interest around NICE and FibroScan use, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
In a monumental moment for combatting Fatty Liver disease, NICE has published the much anticipated evidence-based recommendations on FibroScan for assessing liver fibrosis and cirrhosis outside secondary and specialist care. Such a positive announcement comes at no better time than the start of the Surfing NASH ongoing coverage of International #NASHDay 2023 . To kick off the occasion, this first episode features hepatology researcher and KOL, William Alazawi, and new guest Vanessa Hebditch who serves as Director of Communications and Policy at the British Liver Trust. The panelists, alongside Louise Campbell and Roger Green, celebrate and comment on the new guidance on FibroScan use in the UK.
Roger starts this conversation with a metaphor suggesting that as the FibroScan initiative takes shape, different stakeholders and communities might start out in different directions. Later, Louise suggests that the regions should rethink their funding to make it, as she puts it, bottom up instead of top down, and discusses other steps necessary to equalize delivery of quality scanning care throughout the US. Louise also mentions that the NHS recently announced investment in community scanning centers over the next two years in making all this work. The conversation winds down with Vanessa talking about work the British Liver Trust has done to assess different regions abilities to analyze and act on abnormal tests and more recently, conversations with integrated care boards on this topic. She goes on to discuss some of the challenges with producing change within NHS.
If you have questions or interest around NICE and FibroScan use, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
In a monumental moment for combatting Fatty Liver disease, NICE has published the much anticipated evidence-based recommendations on FibroScan for assessing liver fibrosis and cirrhosis outside secondary and specialist care. Such a positive announcement comes at no better time than during the Surfing NASH coverage of International #NASHDay 2023 . This conversation features hepatology researcher and KOL, William Alazawi, and new guest Vanessa Hebditch who serves as Director of Communications and Policy at the British Liver Trust. The panelists, alongside Louise Campbell and Roger Green, celebrate and comment on the new guidance on FibroScan use in the UK.
This conversation starts with Roger providing a brief background on the Surfing NASH coverage of the NICE-FibroScan question. Vanessa is invited to share the work that her organization has done on this issue. She starts by describing the obligation that NICE has to take feedback from multiple stakeholders. She details a 16-month history of the discussion around this issue and the British Liver Trust's role in it. In the process, Vanessa elaborates on the value of anecdotes and patient-centered data in persuading NICE committees to think more expansively about the value of FibroScan and facilitating an alliance of professional societies in support of this campaign. Louise notes how revisions in data and models coupled with new perspectives led to a change in the NICE vision over time and produced this result. Will discusses the value of FibroScan and preventive hepatology, asserting that the level and nature of necessary data to prove the value of this intervention does not yet exist. He says that at the same time advocates promote use, these same stakeholders should "put our feet to the fire to produce evidence that will support the activity." Louise agrees and notes that the protocols will require those doing the scans to be trained and then assessed to assure quality. Finally, she agrees with Will that the stakeholders need to collect data from all locations to assure quality and that no such process exists today. Roger points out that previously on the podcast, Jeff Lazarus reported back in 2021 that the UK scored higher than any other country in its preparation for the NASH pandemic. Although it scored only 50 points on a 100-point scale, the joint NICE Guidance and NHS Funding initiative have the potential to boost that score significantly and start to build a demonstration model for other countries. Done right, it's an exciting, albeit challenging prospect.
If you have questions or interest around NICE and FibroScan use, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
In a monumental moment for combatting Fatty Liver disease, NICE has published the much anticipated evidence-based recommendations on FibroScan for assessing liver fibrosis and cirrhosis outside secondary and specialist care. Such a positive announcement comes at no better time than the start of the Surfing NASH ongoing coverage of International #NASHDay 2023 . To kick off the occasion, this first episode features hepatology researcher and KOL, William Alazawi, and new guest Vanessa Hebditch who serves as Director of Communications and Policy at the British Liver Trust. The panelists, alongside Louise Campbell and Roger Green, celebrate and comment on the new guidance on FibroScan use in the UK.
This conversation continues focus on the concerns around appropriate data collection and analysis to discover the best path forward. Will describes the need to collect the kinds of data that will assess the value of the process and the right way to execute as processes are built and implemented. Vanessa agrees, but asks that we not let the perfect be the enemy of the good and that we keep in mind how many patients with advanced fibrosis are not getting diagnosed today and need the support of this program. One point that clearly emerges in dialogue with Will is that other countries will look to NICE and the UK experience to inform their own decisions. This only amplifies the need to collect data well and wisely. Louise states that she would also like to see data about the effect of this initiative on related metabolic conditions. She likens FibroScan scoring to dropping a pebble in a pond and seeks to explore the ripples it makes in related diseases and conditions, particularly for endocrinology and cardiology. Roger remarks on how refreshing it is to hear a conversation where multiple stakeholders are aligned to find the best approach to the disease. He goes on to contrast this topic to the role of ICER. Finally, Roger asks questions around Louise's pond metaphor and mentions comments that Stephen Harrison and Mazen Noureddin made last autumn that had suggested that FAST may be a better first line test. Will suggests that many questions need to be answered before determining the accuracy of the tests or what the best way to perform them is.
If you have questions or interest around NICE and FibroScan use, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
Thursday, June 8 was International #NASHDay 2023 and the podcast hosted a special session featuring patient advocates Gina Villiotti Madison (NASH kNOWledge), Marko Korenjak (European Liver Patients' Association) and Michael Betel (Fatty Liver Alliance). With co-hosts Louise Campbell and Roger Green, the group shares both a positive and sobering discussion around the Fatty Liver public health epidemic and its impact on younger generations now and into the imminent future.
Roger starts this conversation by asking Louise to provide more information about the U.K. Parliament debate that had just commenced. Louise notes that MPs from all parts of the UK participated and that they were extremely well-informed on childhood NAFLD and other issues. She notes that members told stories of their own weight loss and government promise to brief MPs on liver disease on an interim basis going forward. One MP said he did not like the term living with obesity, which is considered patient sensitive, because it implies that obesity is a permanent condition. This leads to Roger's closing question which asks each panelist to envision what their organizations' key 2024 International #NASHDay activities might be. While their answer are aligned with what they did for the International #NASHDay 2023, listen for some different twists and new directions.
This is a particularly important and moving episode that captures a range of topics pertinent to the patient perspective and, more broadly, stepping up to NASH. If you have questions or interest around the International #NASHDay 2023, we kindly ask that you submit reviews wherever you download our discussions. Alternatively, you can write to us directly at questions@SurfingNASH.com. We welcome all stories around how you and your community stepped up to NASH this year and look forward to broadening the discourse.
Stay Safe and Surf On!This episode was generously sponsored by Madrigal Pharmaceuticals.Madrigal Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company pursuing novel therapeutics for nonalcoholic steatohepatitis (NASH), a liver disease with high unmet medical need. Madrigal’s lead candidate, resmetirom, is a once daily, oral, thyroid hormone receptor (THR)-β selective agonist designed to target key underlying causes of NASH in the liver. For more information, visit www.madrigalpharma.com.
Thursday, June 8 was International #NASHDay 2023 and the podcast hosted a special session featuring patient advocates Gina Villiotti Madison (NASH kNOWledge), Marko Korenjak (European Liver Patients' Association) and Michael Betel (Fatty Liver Alliance). With co-hosts Louise Campbell and Roger Green, the group shares both a positive and sobering discussion around the Fatty Liver public health epidemic and its impact on younger generations now and into the imminent future.
Roger starts this conversation by asking the panel about other groups and organizations each is working to reach in an effort to increase education and awareness. The first observations revolve around efforts in the UK to take FibroScan into the public domain based on NHS funding of community centers and the NICE guidance about the economic value of FibroScan use outside of the specialist clinics and in primary settings. Louise believes that this will improve frontline patient education with the FibroScan scores and offer an opportunity to educate and motivate people who want to know their liver health. She mentions Naim Alkhouri's discussion of FibroScan as the fifth vital sign in his discussion with Donna Cryer as part of International #NASHDay. Louise then amplifies on her dialogs and opportunities she sees with patients she scans today. Roger asks about the socioeconomic status of the people she scans. She notes that her patients are higher in socioeconomic status and patients who are lower on socioeconomic status tend to have more disease. She questions whether this is solely about diet or also about the far broader opportunities that higher socioeconomic status patients have to active lifestyles. Gina comments that she encounters lots of people who are unaware of the true caloric contents of their diets, especially in terms of sugar intake. She also notes that ultra-processed foods are far more affordable than organic fresh produce, for example. Eventually, Gina discusses how sugar in drinks can contribute to a public health epidemic unrecognized by many parents. As the conversation winds down, Roger asks Marko about the different activities he sees in the 30 EU countries that ELPA represents. He talks about a walking and learning program in Cyprus among other activities. Finally, he pinpoints the ages between 18 to 35 as the key years to adopt good habits.
This is a particularly important and moving episode that captures a range of topics pertinent to the patient perspective and, more broadly, stepping up to NASH. If you have questions or interest around the International #NASHDay 2023, we kindly ask that you submit reviews wherever you download our discussions. Alternatively, you can write to us directly at questions@SurfingNASH.com. We welcome all stories around how you and your community stepped up to NASH this year and look forward to broadening the discourse.
Stay Safe and Surf On!This episode was generously sponsored by Madrigal Pharmaceuticals.Madrigal Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company pursuing novel therapeutics for nonalcoholic steatohepatitis (NASH), a liver disease with high unmet medical need. Madrigal’s lead candidate, resmetirom, is a once daily, oral, thyroid hormone receptor (THR)-β selective agonist designed to target key underlying causes of NASH in the liver. For more information, visit www.madrigalpharma.com.
Thursday, June 8 was International #NASHDay 2023 and the podcast hosted a special session featuring patient advocates Gina Villiotti Madison (NASH kNOWledge), Marko Korenjak (European Liver Patients' Association) and Michael Betel (Fatty Liver Alliance). With co-hosts Louise Campbell and Roger Green, the group shares both a positive and sobering discussion around the Fatty Liver public health epidemic and its impact on younger generations now and into the imminent future.
In this conversation, the group focuses discussion around adolescent NAFLD/NASH. Roger begins by mentioning how the way his generation grew up involved ample time outdoors playing. He goes on to note two differences between then and now. First, the perception that outside areas are not as safe as they once were. Second, Roger underscores the rise of indoor video and online games that occupy the time and attention of children today. Roger asks whether and how we can reverse this trend, particularly when it involves different parents who might work 10 to 12 hours a day. Louise suggests this will be difficult because while outdoor play is no less safe than in past decades, social media has increased the fear that children are unsafe outdoors. After the group jokes about how the presence of wireless television remotes contributed to less active lifestyles, Roger comments on how news cycles operate in the US today.
Michael discusses the role of governments in improving information on food labelling. This leads Gina to note that as a mother, it was only recently that she realized the extent of the health challenges presented by the food her children were eating both at home and at school. She goes on to describe how and why NASH kNOWledge focuses so much attention on children. One idea is that educating children is an excellent way of transmitting information to the entire family. Gina cites the success of public service advertising on school education at getting children to talk with their parents about quitting smoking in past years. It's her hope that we can achieve the same benefits regarding food and exercise. Tune into the subsequent conversations to listen to more comments around sugar intake.
This is a particularly important and moving episode that captures a range of topics pertinent to the patient perspective and, more broadly, stepping up to NASH. If you have questions or interest around the International #NASHDay 2023, we kindly ask that you submit reviews wherever you download our discussions. Alternatively, you can write to us directly at questions@SurfingNASH.com. We welcome all stories around how you and your community stepped up to NASH this year and look forward to broadening the discourse.
Stay Safe and Surf On!This episode was generously sponsored by Madrigal Pharmaceuticals.Madrigal Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company pursuing novel therapeutics for nonalcoholic steatohepatitis (NASH), a liver disease with high unmet medical need. Madrigal’s lead candidate, resmetirom, is a once daily, oral, thyroid hormone receptor (THR)-β selective agonist designed to target key underlying causes of NASH in the liver. For more information, visit www.madrigalpharma.com.
Thursday, June 8 was International #NASHDay 2023 and the podcast hosted a special session featuring patient advocates Gina Villiotti Madison (NASH kNOWledge), Marko Korenjak (European Liver Patients' Association) and Michael Betel (Fatty Liver Alliance). With co-hosts Louise Campbell and Roger Green, the group shares both a positive and sobering discussion around the Fatty Liver public health epidemic and its impact on younger generations now and into the imminent future.
This conversation starts with Roger asking each of panelist to describe the activities that their organizations have undertaken as part of International #NASHDay. Gina leads by talking about two of her organization's activities in the Pittsburgh area. First, the NASH kNOWledge released a video playing on the theme of Step Up for NASH. The fun video features simple dance steps and routines by organization leaders and volunteers. Second, NASH kNOWledge sponsored an event Thursday evening focused on the Hispanic community, where NAFLD is significant and under-managed disease. Gina goes on to discuss the organization's overall commitment to the Hispanic community.
Michael discusses the range of interviews he has been doing with major organizations as well as an in-person event Thursday night in the Ottawa area. On Saturday, Fatty Liver Alliance plans a full day community event. Marko next notes that ELPA decided to make June a Fatty Liver Month initiative triggered by multiple online posts designed to get the attention of leaders throughout the European Union. On International #NASHDay ELPA held an event at the EU parliament in Brussels with patients and speakers from ten different countries. Marko closes his comments by noting that when ELPA talks to parliament members about adult NAFLD, they are far less interested than when he ELPA discusses a childhood disease. This leads Roger to ask whether talking about children is a motivator to legislators and key figures in other countries, and if so, why? As the conversation winds down, Louise discusses motivations in the UK built around projections of declining life expectancy, coupled with the fact that 39% of obese UK patients have an NAFLD. The rest of the panelists follow by sharing their own perspectives which align with Roger's observation and Louise's comments.
This is a particularly important and moving episode that captures a range of topics pertinent to the patient perspective and, more broadly, stepping up to NASH. If you have questions or interest around the International #NASHDay 2023, we kindly ask that you submit reviews wherever you download our discussions. Alternatively, you can write to us directly at questions@SurfingNASH.com. We welcome all stories around how you and your community stepped up to NASH this year and look forward to broadening the discourse.
Stay Safe and Surf On!This episode was generously sponsored by Madrigal Pharmaceuticals.Madrigal Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company pursuing novel therapeutics for nonalcoholic steatohepatitis (NASH), a liver disease with high unmet medical need. Madrigal’s lead candidate, resmetirom, is a once daily, oral, thyroid hormone receptor (THR)-β selective agonist designed to target key underlying causes of NASH in the liver. For more information, visit www.madrigalpharma.com.
Thursday, June 8 was International #NASHDay 2023 and the podcast hosted a special session featuring patient advocates Gina Villiotti Madison (NASH kNOWledge), Marko Korenjak (European Liver Patients' Association) and Michael Betel (Fatty Liver Alliance). With co-hosts Louise Campbell and Roger Green, the group shares both a positive and sobering discussion around the Fatty Liver public health epidemic and its impact on younger generations now and into the imminent future. Each guest discusses what their respective organizations are doing in support of International #NASHDay and the conversations that follow invoke a sense of urgency to take action as a community. This is a particularly important and moving episode that captures a range of topics pertinent to the patient perspective and, more broadly, stepping up to NASH.
If you have questions or interest around the International #NASHDay 2023, we kindly ask that you submit reviews wherever you download our discussions. Alternatively, you can write to us directly at questions@SurfingNASH.com. We welcome all stories around how you and your community stepped up to NASH this year and look forward to broadening the discourse.
**Stay Safe and Surf On!
This episode was generously sponsored by Madrigal Pharmaceuticals.Madrigal Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company pursuing novel therapeutics for nonalcoholic steatohepatitis (NASH), a liver disease with high unmet medical need. Madrigal’s lead candidate, resmetirom, is a once daily, oral, thyroid hormone receptor (THR)-β selective agonist designed to target key underlying causes of NASH in the liver. For more information, visit *www.madrigalpharma.com.*
In a monumental moment for combatting Fatty Liver disease, NICE has published the much anticipated evidence-based recommendations on FibroScan for assessing liver fibrosis and cirrhosis outside secondary and specialist care. Such a positive announcement comes at no better time than the start of the Surfing NASH ongoing coverage of International #NASHDay 2023 . To kick off the occasion, this first episode features hepatology researcher and KOL, William Alazawi, and new guest Vanessa Hebditch who serves as Director of Communications and Policy at the British Liver Trust. The panelists, alongside Louise Campbell and Roger Green, celebrate and comment on the new guidance on FibroScan use in the UK.
In addition, stay tuned for a session dedicated to International #NASHDay 2023 which will be released on Friday June 9th. If you have questions or interest around the event or FibroScan use, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
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On May 6 and 7 2022, over 100 NAFLD stakeholders convened in Barcelona and on-line for the inaugural Innovations in NAFLD Care 2022 conference (#INCBCN.) Surfing the NASH Tsunami was there, with Jörn Schattenberg serving as event co-chair and Louise Campbell and Roger Green moderating sessions. This episode From the Vault is less a formal recap of the meeting than recollections of key moments and messages from the co-founders and Surfers.
This discussion starts with #INCBCN co-founder Jeff Lazarus and Roger Green what Jeff considered the successes and surprises of the conference. Jeff speaks about the “palpable” energy of the attendees, the number of people who attended virtually and engaged through Q & A and the range of issued addressed at the conference as three strong positives. On a more prosaic note, he also mentions how well the technology worked throughout the meeting. Roger Green suggests that much of the energy came from merging three separate streams of activity — medical specialists, primary care and patient advocates — into a single conversation that touched on all three groups’ issues. He also suggests that having Marcus Ranney and Jeff to share a digital health vision of the future added additional energy and the prospect of what Roger calls “radical patient empowerment.” As co-founder Jörn Schattenberg and then Louise Campbell join the conversation, levity ensues as the four discuss the surprise closing statement from Jeff and Jörn and then a more serious tone as the group discusses the benefits that multidisciplinary conversation brought to all the participants.
Surfing NASH returns to review the 2023 Innovations in NAFLD Care Workshop (INCBCN) which concluded on 27 May in Barcelona. Conference founders and directors Jeff Lazarus and Jörn Schattenberg discuss highlights and takeaways of the event with Louise Campbell and Roger Green.
This closing conversation continues to cover the highlights of the second day, including the EU Pearl program and the debate about the value of curing NAFLD and NASH with a vegetarian diet or not. The session goes on to capture final thoughts and ideas which will be carried over into future programs. Listen on to hear each respond to a set of closing questions around a truly unique and innovative program.
If you have questions or interest around the Innovations in NAFLD Care Workshop 2023, we kindly ask that you submit reviews wherever you download our discussions. Alternatively, you can write to us directly at questions@SurfingNASH.com.
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Surfing NASH returns to review the 2023 Innovations in NAFLD Care Workshop (INCBCN) which concluded on 27 May in Barcelona. Conference founders and directors Jeff Lazarus and Jörn Schattenberg discuss highlights and takeaways of the event with Louise Campbell and Roger Green.
This conversation starts with Jeff commenting on patient needs and a specific question which Alina Allen raised around whether people should be diagnosed earlier and do the harms outweigh the benefits? Jeff notes that this is a significant mistake, recalling his own experiences with the Hep-C community. The group next detours briefly into the impact that the FDA ADCOM on obeticholic acid has on all of these issues before shifting to discuss the second day. Jörn talks about the idea that while there were a limited number of posters at the meeting, the posters that were there were excellent and engaging in the way that researchers could discuss them in detail. Jeff summarizes Alina Allen's talk about how to use AI and diagnostics. Jörn points out that we need more standardized patient reports if we were to use this data in AI because the data has to be standardized to take advantage of it. The end of the session takes an entertaining twist, so listen on to find out more.
If you have questions or interest around the Innovations in NAFLD Care Workshop 2023, we kindly ask that you submit reviews wherever you download our discussions. Alternatively, you can write to us directly at questions@SurfingNASH.com.
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Surfing NASH returns to review the 2023 Innovations in NAFLD Care Workshop (INCBCN) which concluded on 27 May in Barcelona. Conference founders and directors Jeff Lazarus and Jörn Schattenberg discuss highlights and takeaways of the event with Louise Campbell and Roger Green.
This conversation revolves around the term preventive hepatology which was the focus of a roundtable. Roger asks whether taking a FibroScan into the community qualifies as preventive hepatology. Jörn suggests it might so long as the patient is properly identified. Jeff identifies one of the earliest papers on preventive hepatology from 2008 titled Minimizing symptoms and optimizing care. He goes on to promote the idea that the process of prevention needs to start earlier. This leads Roger to point to a moment of constructive disagreement in the meeting. He suggests that preventive hepatology needs to actually start before the patient ever gets to the hepatologist. Jeff mostly agrees and notes that on one level it all starts with Sustainable Development Goals outlined by WHO. Louise describes the idea that preventive hepatology is about more than the liver alone which leads Roger to throw out the term preventative metabolic health. Jörn suggests this to be an excellent ideal, but in a siloed health system we have to start by bringing disciplines together to break down those silos as INCBCN is designed to do.
As the session winds down, the group comments on the endocrinology session that Rising Tide co-host Ken Cusi chaired. The audience enjoyed seeing how these endocrinologists are focused on fatty liver disease with what Jörn describes as a practical view on extending liver care and management.
Listen on to discover the details revealed in the full episode. If you have questions or interest around the Innovations in NAFLD Care Workshop 2023, we kindly ask that you submit reviews wherever you download our discussions. Alternatively, you can write to us directly at questions@SurfingNASH.com.
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Surfing NASH returns to review the 2023 Innovations in NAFLD Care Workshop (INCBCN) which concluded on 27 May in Barcelona. Conference founders and directors Jeff Lazarus and Jörn Schattenberg discuss highlights and takeaways of the event with Louise Campbell and Roger Green.
This conversation starts with a focus on the opening session which is titled The Fatal Triple and End-Organ Injury. Embedded in the recap is the topic of alcohol consumption and how it contributes to Fatty Liver disease. The idea emerges that a standard unit of drink varies in definition and that there may be benefit to gathering structured consensus on the definition. The second part of this conversation considers facilitating FibroScan testing in different patient settings.
Listen on to discover the details revealed in the full episode. If you have questions or interest around the Innovations in NAFLD Care Workshop 2023, we kindly ask that you submit reviews wherever you download our discussions. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
Surfing NASH returns to review the 2023 Innovations in NAFLD Care Workshop (INCBCN) which concluded on 27 May in Barcelona. Conference founders and directors Jeff Lazarus and Jörn Schattenberg discuss highlights and takeaways of the event with Louise Campbell and Roger Green.
This conversation captures the meeting in a broad sense by outlining its goals and reason for being. Jeff describes this year’s emphasis on expanding the community of practice beyond hepatology. For example, friend of the podcast and co-host of our Rising Tide series, Ken Cusi, chaired a session on the role of endocrinology and diabetology in the early diagnosis and management of NASH. In Jeff’s words, “We were trying to look at the liver more holistically and look at who else should be involved in a multidisciplinary approach.”
The discussion shifts to a review of the NASH-NITs Real-World-Evidence Summit. Jörn suggests that moving forward, the Summit ought to be expanded and broadened. After Jörn comments on the positive experience of facilitating hands-on engagement, Louise offers her take. She underscores that FibroScan testing requires adequate knowledge and training to be well-executed with precision. The group goes on to describe in detail what made the Summit unique and how it might grow in the future.
Listen on to discover the details revealed in the full episode. If you have questions or interest around the Innovations in NAFLD Care Workshop 2023, we kindly ask that you submit reviews wherever you download our discussions. Alternatively, you can write to us directly at questions@SurfingNASH.com.
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Surfing NASH returns to review the second Innovations in NAFLD Care Workshop (INCBCN) which concluded on 27 May in Barcelona. Conference founders and directors Jeff Lazarus and Jörn Schattenberg discuss highlights and takeaways of the event with Louise Campbell and Roger Green.
00:00 Introduction 06:14 Holistic thinking and expanding the community of practice 08:00 NASH-NIT Real World Evidence Summit 09:48 Louise on FibroScan proficiency 15:02 The Fatal Triple 18:52 Alcohol consumption and consensus around standards of drink 24:12 Exploring ideas of preventative hepatology 31:38 Session 2: Endocrinology and Diabetology in the early diagnosis and management of NASH 35:43 Poster presentations
37:02 Session 3: NAFLD Diagnostics 40:42 Session 4: NAFLD Treatment and Care
47:13 Closing question: any surprising audience responses?Listen on to discover the details as revealed in the full episode. If you have questions or interest around the Innovations in NAFLD Care Workshop 2023, we kindly ask that you submit reviews wherever you download our discussions. Alternatively, you can write to us directly at questions@SurfingNASH.com.
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The first three days of the 2022 program focused on a range of issues, with specific emphasis on non-invasive tests (NITs) and their role at different stages in diagnosis and treatment. This conversation From the Vault touches on two issues: use of AI to better understand the meaning of liver volume and elements of morphology and, relatedly, how much more sophisticated a view we take of NAFLD and NASH than we did even five years ago.
The issues around AI and liver morphology arise from Jörn Schattenberg’s comment that consistent with Stephen Harrison’s “KISS” (Keep It Simple, Stupid!) principle, researchers are starting to explore the meaning of changes in liver volume. Ultimately, Jörn notes, pairing these kinds of measures to AI-supported histopathology can yield tremendous benefits. Roger comments on a breakfast he attended that morning that suggested that AI and NITs each provide different, important information on individual liver health: NITs can address collagen burden but not structure, while AI can identify changes in structure but not link them to the impact on the patient. Zobair ends this part of the conversation by noting that companies are starting to use AI in these ways.
The second part of this conversation stems from Roger’s observation that we know far more about the disease than we did 3-4 years ago. He goes on to describe how the environment is more collaborative and open-minded than it might have been if, in fact, we saw drug approvals at that time. Zobair takes this observation to a different plane, noting that 5-10 years ago, “some very important experts” believed that we all understood the etiology of Fatty Liver disease, so why spend more time? He goes on, “we could not have been more wrong,” observing that what we have learned about progression and regression in placebo arms suggests a far more complex disease than something that progresses linearly, or even constantly in one direction. He goes on to add that the multiple drug trial failures is that targeting drugs to a single solution based on animal models is likely to fail because this is a multiple mode of action disease. His third point: the “source” of the disease is visceral obesity and insulin resistance, which all viable solutions must address. This identifies two targets for treatment, while simultaneously demonstrating that therapy will be chronic, lifelong and with behavioral elements. The rest of the conversation addresses the challenges with shaping this kind of lifelong, multitarget therapy in the US today.
Surfing NASH offers an exciting preview of EASL Congress 2023 with new guest and EASL Vice-Secretary, Aleksander Krag, alongside EASL Educational Councillor, Sven Francque, and Surfers Jörn Schattenberg, Louise Campbell and Roger Green. The world’s largest liver meeting takes place 21-24 June in Vienna with an international faculty of experts from over 200 institutions. The diverse program will feature 2500 abstracts and be a uniquely momentous occasion for developing multidisciplinary approaches aimed at putting a major dent in Fatty Liver disease.
This final session starts with Roger sharing his appreciation for conversational opportunities that emerge from poster presentations at major meetings. The other panelists agree in their own ways that the presentations produce invaluable dialogue to bridge researchers and students over emerging science. From here, the conversation considers what about the virtual component of this meeting is unique and worth attending before moving on to final thoughts. Each recaps their excitement at a high level from differing perspectives and points of interest. Surf on to find out what they are.
If you enjoy the episode, have questions or interest around EASL Congress 2023 and Fatty Liver disease, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
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Surfing NASH offers an exciting preview of EASL Congress 2023 with new guest and EASL Vice-Secretary, Aleksander Krag, alongside EASL Educational Councillor, Sven Francque, and Surfers Jörn Schattenberg, Louise Campbell and Roger Green. The world’s largest liver meeting takes place 21-24 June in Vienna with an international faculty of experts from over 200 institutions. The diverse program will feature 2500 abstracts and be a uniquely momentous occasion for developing multidisciplinary approaches aimed at putting a major dent in Fatty Liver disease.
This conversation starts with Roger’s question to Sven around his role as Educational Councillor and the various educational opportunities embedded within the program. Sven first describes a postgraduate course that focuses on the link between NAFLD and cancer. He goes on to describe a plethora of activities which each embody different levels of education and participation for different stakeholder groups. Notably, he underscores the goal of broadening education to reach parties external to specialist hepatology groups. This is not only about raising awareness, but also engaging communities with the concept of liver health from a very young age. Roger asks what the balance is between virtual and onsite attendance and Aleksander suggests people are trending back to onsite participation. The group discusses why in-person attendance is especially positive for the previously described educational elements. From here Roger asks Aleksander and Sven for their lists of “3 things you can’t miss” for different participating groups. First, he asks what’s not to be missed for a recently minted transplant hepatologist. Next, he shifts focus to what’s not to be missed for attending students.
The conversation shifts to questions from Louise and Jörn which focus on how the program was put together. It becomes clear that this is a multifaceted event that combines the experiences of education, networking, science development and much more. Aleksander likens the meeting to a giant dinner party whereby the organizers are chefs who have taken a year to prepare an extravagant meal for thousands to enjoy. For the remainder of the session, Louise leans in on a comment Aleksander makes about allied health and points out that there are some very good and important sessions around health literacy.
If you enjoy the episode, have questions or interest around EASL Congress 2023 and Fatty Liver disease, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
Surfing NASH offers an exciting preview of EASL Congress 2023 with new guest and EASL Vice-Secretary, Aleksander Krag, alongside EASL Educational Councillor, Sven Francque, and Surfers Jörn Schattenberg, Louise Campbell and Roger Green. The world’s largest liver meeting takes place 21-24 June in Vienna with an international faculty of experts from over 200 institutions. The diverse program will feature 2500 abstracts and be a uniquely momentous occasion for developing multidisciplinary approaches aimed at putting a major dent in Fatty Liver disease.
This conversation begins with Jörn describing his anticipations for the meeting where he will be Chair of two separate sessions. One such session of interest will be in the context of a Meet the Experts panel on lean NASH. He also goes on to note excitement for late breakers and learning about novel compounds and newly emerging Phase 3 results. In summary, Jörn describes EASL Congress as “the place where we really shape the future of NAFLD therapy.”
From here Louise highlights her interest in virtually viewing sessions on patients and advocacy and nurses and allied health. Aleksander notes an emphasis in this year’s agenda on having interactive, hands-on elements to participate with. For example, there will be educational opportunities to engage the community with learning how to administer FibroScan. Roger notes the EASL Studio as a capturing component to look out for this year. There will be two studios: one around new treatments, pathways and drug development, and the other dedicated to nomenclature. Roger goes on to describe his personal interest in discovering the latest directions of drug development and noninvasive testing. As the session winds down, Aleksander delivers a comprehensive and compelling list of important activities to be on the lookout for. Surf on to discover what they are.
If you enjoy the episode, have questions or interest around EASL Congress 2023 and Fatty Liver disease, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
Surfing NASH offers an exciting preview of EASL Congress 2023 with new guest and EASL Vice-Secretary, Aleksander Krag, alongside EASL Educational Councillor, Sven Francque, and Surfers Jörn Schattenberg, Louise Campbell and Roger Green. The world’s largest liver meeting takes place 21-24 June in Vienna with an international faculty of experts from over 200 institutions. The diverse program will feature 2500 abstracts and be a uniquely momentous occasion for developing multidisciplinary approaches aimed at putting a major dent in Fatty Liver disease.
In this conversation, the audience is introduced to Aleksander and his work in Fatty Liver disease. He describes a career trajectory which began in gastroenterology before becoming enthralled with the variations and challenges associated with the liver. Aleksander goes on to recall a defining moment when he had an abstract accepted for EASL. “Suddenly I was there among equally minded people from all over the world. Wasn’t that just amazing?” Now fully integrated into the global liver family, Aleksander enjoys being a leader who drives inspiration into the next generation of hepatologists and collaborating with all stakeholders to create a future with better liver care. After serving two years as Vice-Secretary of the EASL Congress, Aleksander will become the Secretary General for the term of 2023-2025.
From here, the conversation observes a few particular elements of this year’s meeting that will make it a special one. Aleksander highlights that the meeting has “never been wider” with a diverse lineup of contributors and collaborators which expands engagement beyond abstracts and Phase 3 trial launches. Specifically, he describes outreach activities that deliver liver screenings to the streets and provide education to local schools on nutrition and the importance of liver health. Sven adds that there is something for everyone here, be it related to nurses, patients, industry or science. All in all, when compared to previous meetings both Sven and Aleksander instill a bubbling excitement that leaves the audience with high expectations.
Listen to the full feature for the most detailed preview of the event and follow along as the Surfers convene for live coverage. If you enjoy the episode, have questions or interest around EASL Congress 2023 and Fatty Liver disease, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
Surfing NASH offers an exciting preview of EASL Congress 2023 with new guest and EASL Vice-Secretary, Aleksander Krag, alongside EASL Educational Councillor, Sven Francque, and Surfers Jörn Schattenberg, Louise Campbell and Roger Green. The world’s largest liver meeting takes place 21-24 June in Vienna with an international faculty of experts from over 200 institutions. The diverse program will feature 2500 abstracts and be a uniquely momentous occasion for developing multidisciplinary approaches aimed at putting a major dent in Fatty Liver disease.
In this conversation, the audience is introduced to Aleksander and his work in Fatty Liver disease. He describes a career trajectory which began in gastroenterology before becoming enthralled with the variations and challenges associated with the liver. Aleksander goes on to recall a defining moment when he had an abstract accepted for EASL. “Suddenly I was there among equally minded people from all over the world. Wasn’t that just amazing?” Now fully integrated into the global liver family, Aleksander enjoys being a leader who drives inspiration into the next generation of hepatologists and collaborating with all stakeholders to create a future with better liver care. After serving two years as Vice-Secretary of the EASL Congress, Aleksander will become the Secretary General for the term of 2023-2025.
From here, the conversation observes a few particular elements of this year’s meeting that will make it a special one. Aleksander highlights that the meeting has “never been wider” with a diverse lineup of contributors and collaborators which expands engagement beyond abstracts and Phase 3 trial launches. Specifically, he describes outreach activities that deliver liver screenings to the streets and provide education to local schools on nutrition and the importance of liver health. Sven adds that there is something for everyone here, be it related to nurses, patients, industry or science. All in all, when compared to previous meetings both Sven and Aleksander instill a bubbling excitement that leaves the audience with high expectations.
Listen to the full feature for the most detailed preview of the event and follow along as the Surfers convene for live coverage. If you enjoy the episode, have questions or interest around EASL Congress 2023 and Fatty Liver disease, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
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Stephen Harrison joins Louise Campbell and Roger Green for an insight-laden episode about challenges and opportunities in NASH drug development. This final conversation unpacks a stimulating deep dive into the science and strategy behind quantitating and reducing hepatocellular ballooning. As for the closing question, Roger asks what will be the biggest difference to emerge in trial execution design over the next two years. Stephen begins his response with the suggestion that AI-assisted pathology could one day be a potential surrogate endpoint. Tune in to find out how and why.
If you enjoy the episode, have questions or interest around NASH therapeutic development, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
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Stephen Harrison joins Louise Campbell and Roger Green for an insight-laden episode about challenges and opportunities in NASH drug development. This conversation continues from the preceding discussion on screen fail rates. Louise starts by asking what would the ideal patient look like for an attempt at lowering screen fail rates. Stephen responds with two assertions. The first suggestion is that higher hemoglobin A1C is indicative of disease activity in the fibrosis needed to qualify. Second, Stephen identifies utility in retrieving a FibroScan-AST score as a promising prescreen strategy. From here the conversation considers the variability of liver biopsy and whether there is a convincing impetus for establishing guidelines on the biopsy reading process. As the session winds down, Roger raises the idea that hepatocellular ballooning should be considered as a continuous variable. This proposition primes the following and final conversation to dive deep into the science and art of pathology reading.
If you enjoy the episode, have questions or interest around NASH therapeutic development, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
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Stephen Harrison joins Louise Campbell and Roger Green for an insight-laden episode about challenges and opportunities in NASH drug development. This conversation breaks away from commentary around the FDA ADCOM meeting on obeticholic acid after Louise begins with a synopsis of the meeting outcome and her general agreement with the preceding conversation’s analysis. From there Roger shifts focus to a powerhouse paper produced by Stephen (and co-authored by friends of the podcast Alina Allen, Julie Dubourg, Mazen Noureddin and Naim Alkhouri) which was published in Nature Medicine earlier in March 2023. When asked what would be the one or two sentences that could best capture it, Stephen simply suggests the title says it all. “There are tremendous amounts of challenges we're faced with in drug development, but those are equally matched by opportunities.” He goes on to tease that the upcoming EASL Congress in Vienna will provide a venue to unpack pioneering insights which will inform new directions in a rapidly moving field. Specifically, Stephen points to interest in what’s emerging from AI-assisted digital pathology. He underscores the role of AI-assisted digital pathology to be pivotal in ushering in a new generation of NITs. “We need to fully understand how effective our noninvasive tests are in… diagnosis monitoring, response to therapy, predicting outcomes and predicting the magnitude of effect change that links not to biopsy but to an outcome measure.”
On the back end of this session, Roger asks whether there is a specific subject or sector that will catalyze our understanding and management of patients with Fatty Liver. Stephen immediately points to the diabetic population as a set of patients that are going to allow the field to advance quicker. He reasons that endocrinologists are also working intently to better understand and solve this issue. The remainder of the conversation transitions to the topic of screen fail rates.
If you enjoy the episode, have questions or interest around NASH therapeutic development, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
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Stephen Harrison joins Louise Campbell and Roger Green for an insight-laden episode about challenges and opportunities in NASH drug development. This first conversation begins with an update from Stephen on what he has been working on since last appearing on the podcast. He notes new and exciting data emerging from NGM on aldafermin, an FGF19, which indicates that multiple different mechanisms are demonstrating a positive impact on cirrhosis. Stephen shares that he is “becoming more convinced that we can move the needle in this toughest to treat patient population, albeit prior to them developing decompensating disease. There is hope that this population is not too far gone and we can be impactful.”
From here he goes on to offer an impression on the outcome of FDA’s ADCOM meeting for obeticholic acid as a treatment for pre-cirrhotic fibrosis due to NASH. Among other takeaways, Stephen emphasizes the FDA’s prioritization of safety. If there are safety concerns, there is a need for mitigation strategies to de-risk those concerns. His second point is that statistical significance on a surrogate endpoint does not guarantee conditional approval from the FDA. “The therapeutic index of a drug needs to be such that you're providing a benefit in not having a potential adverse event profile that's similar, if not even higher.” In other words, is the juice worth the squeeze? Stephen suggests that this first drug really has to set the right tone in terms of user friendliness. The ability to readily be adopted by frontline prescribers outside of the hepatology specialty is critical. As a final thought on the subject, Stephen states the appeal behind pleiotropic drugs that can attack multiple different organ systems with a single pill or injection.
If you enjoy the episode, have questions or interest around NASH therapeutic development, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
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This week on Surfing NASH, Stephen Harrison speaks with Louise Campbell and Roger Green about challenges and opportunities in NASH drug development. The conversation comes aptly after the outcome of FDA’s ADCOM meeting for obeticholic acid (OCA) as a treatment for pre-cirrhotic fibrosis due to NASH. The group considers and comments on the safety profile of OCA and what the FDA requires in a first drug approval. However, this session extends much farther to offer a positively stimulating deep dive into the ongoing developments of a range of other therapeutic candidates and research directions for Fatty Liver disease. From the outset, Stephen shares that he is more convinced that we can move the needle in the toughest to treat patient populations prior to them developing decompensating disease. “There is hope that this population is not too far gone and we can be impactful.” Listen on to discover just what is so convincing in this space and what are the elements that give the group hope for the future of Fatty Liver disease.
00:00 Introduction04:26 What has Stephen been working on since last being on the podcast?06:21 Stephen's take on the outcome of the FDA ADCOM meeting on OCA for NASH12:52 Discussing drugs with strong metabolic foundations
16:29 2023 Nature article on challenges and opportunities in NASH drug development21:40 Disease progression in the diabetic population and screen fail rates32:17 Deeper dive into histopathology36:55 Closing question on the future of clinical trial designIf you enjoy the episode, have questions or interest around NASH therapeutic development, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
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On Friday May 19, 2023, an Advisory Committee for the FDA convened to discuss the benefits and risks of obeticholic acid (OCA) 25 mg for treatment of non-alcoholic steatohepatitis (NASH) with fibrosis. As reported in a press release from Intercept Pharmaceuticals, twelve of 16 voting-eligible members of the ADCOM voted “no” (with two abstentions) on the voting question, “given the available efficacy and safety data, do the benefits of OCA 25 mg outweigh the risks in NASH patients with stage 2 or 3 fibrosis?” Fifteen of 16 voting-eligible members (with no abstentions) voted to “defer approval until clinical outcome data from trial 747-303 are submitted and reviewed, at which time the traditional approval pathway could be considered.”In this episode, Founder and CEO of the Global Liver Institute, Donna Cryer, joins Surfers Jörn Schattenberg and Roger Green for a session which draws from raw reflections on the FDA ADCOM meeting and its outcome for OCA. The reactions and discussion that unfold are both sobering and constructive as the group reckons with the unfavorable results and the way forward for the liver community. Critically, the group agrees on the idea that this event simply should not be dubbed “another NASH drug goes down.” Rather, the focus remains on the Committee message that goes, “If a drug under this definition of efficacy has a safety profile where we can trust doctors to be able to manage it, we’ll go with it because we understand the patient needs.” Listen on for the full analysis and stay tuned as Surfing NASH continues its coverage in subsequent episodes this week with different KOLs and stakeholders.
If you enjoy the episode, have questions or interest around the outcome of the FDA ADCOM meeting and OCA, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
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Surfing NASH offers an exciting preview ofEASL Congress 2023 with new guest and EASL Vice-Secretary, Aleksander Krag, alongside EASL Educational Councillor, Sven Francque, and Surfers Jörn Schattenberg, Louise Campbell and Roger Green. The world’s largest liver meeting takes place 21-24 June in Vienna with an international faculty of experts from over 200 institutions. The diverse program will feature 2500 abstracts and be a uniquely momentous occasion for developing multidisciplinary approaches aimed at putting a major dent in Fatty Liver disease. In this lively session, the group covers the following topics and more:
00:00 Introduction and meeting Aleksander Krag
10:22 Sharing first impressions and anticipations around EASL Congress 2023
21:09 Discussing educational opportunities
23:10 Comparing in-person and virtual attendance experiences
24:46 Lists of 3 things "you can't miss" for different participating groups
27:30 Onbuilding the program
29:57 Scientifically stimulating sessions
31:47 Integrating allied health
34:43 The value of posters and engaging students
36:35 Why should anyone attend virtually?
45:04 What will make this meeting special in the end?
Listen to the full feature for the most detailed preview of the event and follow along as the Surfers convene for live coverage. If you enjoy the episode, have questions or interest around EASL Congress 2023 and Fatty Liver disease, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
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The 2022 NAFLD Summit presented a range of perspectives and insights on fatty liver and metabolic diseases. Program speakers Mazen Noureddin, Sven Francque and Hannes Hagström join Surfer, Roger Green, on site from Dublin to review their reactions immediately after the conference ended.
This conversation From the Vault begins with Roger calling attention to a debate around NITs that took place on the opening day of the meeting. Mazen revisits what he has described on this podcast as the coming “combo-combo” world. The group generally agrees that biomarkers in primary care ought to be simple, cost effective and accessible. However, Sven utters a word of caution: while acknowledging the positive potential of NITs, it is still important to evaluate its limitations.
The episode concludes with a round of final reflections. Roger asks for panelists to forecast the most important thing that will have changed between now and when we return for the NAFLD Summit 2023. Surf on to find out what the panel predicts.
This episode is sponsored by Resoundant, a Mayo Clinic company and the developers of Magnetic Resonance Elastography. MRE is widely available with over 2000 locations worldwide, and can be done as a low-cost, rapid exam in just 5 minutes. Together with PDFF, this quantitative exam is called an Hepatogram – a powerful non-invasive alternative to liver biopsy in many cases. For more information, visit www.resoundant.com on the web.
Donna Cryer joins Jörn Schattenberg, Louise Campbell and Roger Green for an impactful episode which weighs the complexities of competing needs across all Fatty Liver stakeholders. The session expands discourse on the recently discussed ICER draft report to consider a developing landscape around nomenclature consensus and other important and impending decisions. Critically, the group grapples with challenges associated with honoring the precedence of patient-centricity.
This final conversation begins with Roger’s note that while patient stories are driven with emotion and impact, the actual patient journey through diagnosis to treatment can unfortunately be a mechanistic and confusing process. With this in mind, Roger asks how do we bring a more holistic sense of what it means to be a patient or patient advocate to all of these issues discussed as they continue to amplify in a bigger, broader way. Donna’s moving response and the various final thoughts from the other panelists encapsulates the need for patients to be respected for the professional skills they possess which can contribute real impact on how the field moves forward in a stronger, more multi-disciplinary fashion. Listen to the full segment to hear the moving statements.
If you enjoy the episode, have questions or interest around endocrinology and Fatty Liver disease, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
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Donna Cryer joins Jörn Schattenberg, Louise Campbell and Roger Green for an impactful episode which weighs the complexities of competing needs across all Fatty Liver stakeholders. The session expands discourse on the recently discussed ICER draft report to consider a developing landscape around nomenclature consensus and other important and impending decisions. Critically, the group grapples with challenges associated with honoring the precedence of patient-centricity.
Donna opens this conversation with several calls to action for patient advocacy in the NASH community. Her first recommendation is to recruit different disciplines to administer and evaluate an impact report regarding nomenclature consensus. Next, and more broadly, she asks all stakeholders to consider how to genuinely and effectively build an inclusive advocacy community. Roger asks Jörn what he believes to be realistic that the field can do for these aims today. First, Jörn notes that many different societies can agree on what is considered to be a severe patient and what an unfavorable outcome is in terms of liver disease. He goes on to say that with therapies in the pipeline and tests like FIB-4 available and widely implementable now, we have indeed come a long way as a field. The risks he perceives with topics such as the ICER draft report and nomenclature consensus revolve around slowing, detouring or dismantling the tremendous progress that has been made. As the session wraps up, Donna offers her thoughts on where this is all heading.
Listen to the full feature to engage with these impactful moments. If you enjoy the episode, have questions or interest around endocrinology and Fatty Liver disease, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
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Donna Cryer joins Jörn Schattenberg, Louise Campbell and Roger Green for an impactful episode which weighs the complexities of competing needs across all Fatty Liver stakeholders. The session expands discourse on the recently discussed ICER draft report to consider a developing landscape around nomenclature consensus and other important and impending decisions. Critically, the group grapples with challenges associated with honoring the precedence of patient-centricity.
Roger begins this conversation by pointing to Jörn’s diversifying role in the NASH community. Specifically, Jörn is prompted to elaborate on his unique perspective in regards to what sort of forward thinking is required in getting “questions asked in a different way.” Jörn first reminds that nomenclature consensus is an ongoing process that has yet to yield a definitive conclusion. More broadly, he goes on to underscore the importance of promoting awareness, education and advocacy around the real impact of Fatty Liver disease on patients and wider communities.
From here the group considers how the nomenclature debate emerged and what cultural and systemic differences may be impacted by a decision going forward. In example, Roger notes that in some countries the word nonalcoholic is useful in that it lifts stigma. The panelists also note the nuances and challenges nomenclature poses to the pediatric population. As the session winds down, Roger states that when dealing with a multi-stakeholder world, you need to start with a truly diffuse, multi-stakeholder solution. Finally, Donna closes with a quote from The Color Purple: “I shouldn't have to fight in my own house. And that's how I feel like as a patient in the NASH community right now.”
Listen to the full feature to engage with these impactful moments. If you enjoy the episode, have questions or interest around endocrinology and Fatty Liver disease, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
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Donna Cryer joins Jörn Schattenberg, Louise Campbell and Roger Green for an impactful episode which weighs the complexities of competing needs across all Fatty Liver stakeholders. The session expands discourse on the recently discussed ICER draft report to consider a developing landscape around nomenclature consensus and other important and impending decisions. Critically, the group grapples with challenges associated with honoring the precedence of patient-centricity.
This conversation begins with Jörn’s response to a preceding and powerful statement by Donna around the undervalued input of the patient community. Roger and Donna go on to define in different ways what and why it is that they are concerned about in both the context of the ICER draft report and the nomenclature consensus process. Roger relates this contention to the sociology of in-groups and out-groups. Louise adds her thoughts from the allied health perspective. Her main point is that the role of the nurse is to “listen to both sides” between the physician and the patient while ultimately serving the patients' “well-being, thoughts, feelings and the way they want things to be portrayed.” Not all patients have advocate family members present in hospitals and therefore critical that nurses and other allied health professionals be supported and present to bolster the patient voice. One way to achieve this would be by featuring stronger presence and representation of these groups in panels.
Listen to the full feature to engage with many more insightful moments. If you enjoy the episode, have questions or interest around endocrinology and Fatty Liver disease, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
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Donna Cryer joins Jörn Schattenberg, Louise Campbell and Roger Green for an impactful episode which weighs the complexities of competing needs across all Fatty Liver stakeholders. The session expands discourse on the recently discussed ICER draft report to consider a developing landscape around nomenclature consensus and other important and impending decisions. Critically, the group grapples with challenges associated with honoring the precedence of patient-centricity.
Roger prefaces this conversation with a brief recap of Season 4 Episode 19 where a panel of patient advocates (Wayne Eskridge, Michael Betel and Anthony Villiotti) dissected glaring inaccuracies and shortcomings within the ICER draft report. Roger goes on to introduce the rollout of the nomenclature consensus work and candidly shares that it is appearing to be a compromised solution between academics. He reasons it's not clear that it takes into account what other stakeholders need and the practicality behind approving drugs, educating patients and moving the management of the disease forward. From here, Donna describes her frustrations with the weight and value allotted (or lack-thereof) to patient inputs on such important matters. Her statement is powerful and urgent, and describing it in words does not capture the gravity of the moment.
Listen to the full feature to engage with many more insightful moments. If you enjoy the episode, have questions or interest around endocrinology and Fatty Liver disease, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
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This week, Donna Cryer (Global Liver Institute) joins Jörn Schattenberg, Louise Campbell and Roger Green for an impassioned and sobering episode which weighs the complexities of competing needs across all Fatty Liver stakeholders. This powerful and at times emotional session expands recent discourse on the ICER draft report to also consider a developing landscape around nomenclature consensus and other important and impending decisions. Critically, the group grapples with challenges associated with honoring the precedence of fighting Fatty Liver through patient-centricity. Among this rich and tremendously honest discussion are the following themes:
00:00 Introduction
07:40 Who is going to be the Larry Kramer of NASH?
17:38 Allied Health for Patient Empowerment
26:59 Generating Data to Demonstrate Patient Needs and Inform Public Health
36:55 Donna’s Call to Action
42:37 Can we absorb enough different perspectives into a common discussion and give them each the weight they deserve?
Listen to the full feature to engage with the many insightful moments. If you enjoy the episode, have questions or interest around patient advocacy, allied health and Fatty Liver disease, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
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On July 7 2022, Intercept Pharmaceuticals released new results from the continuation of the REGENERATE trial and announced their intent to file a new NDA for obeticholic acid (OCA) in NASH fibrosis. In this conversation From the Vault, Stephen Harrison leads Jörn Schattenberg, Louise Campbell and Roger Green in considering whether the evidence in the new release will be sufficient to get the drug approved.
REGENERATE Redux: Clearing The Finish Line?
Stephen starts by noting that we have not heard anything about the results of the REVERSE trial, which evaluated obeticholic acid (OCA) in patients with compensated cirrhosis. As he notes, even if OCA is not approved for cirrhosis, many hepatologists will consider giving this drug to cirrhotic patients, particularly compensated cirrhotics who face a significant worsening of their condition in a fairly short period of time.
Jörn comments on this briefly to agree that the cirrhosis data will create a complete data set, then returns to the pruritus issue. Mostly, his point about cirrhosis is that given the high placebo rate suggests there is “something about how the question is asked.” He finishes this comment by discussing the importance of getting a first drug approved and stating his anticipation of what happens when FDA reviews these data.
Roger goes on to note that he has a unique experience in this group: he has discontinued a drug therapy based on pruritus (in his case, a cancer drug). Having lived through that experience, he expresses skepticism that pruritus that resolves on discontinuation will be a reason for the drug to be rejected. Stephen concurs, and Roger goes on to state that the perceived cardiovascular risk in 2020 made sense as a reason not to approve, but not pruritus. Stephen and Louise concur that we will not know the entire story until we know the lengths to which providers went to keep patients in this study, but both are hopeful (and pretty much expect) that while there may be boundaries on patient types and guidance on treatment, the case for approval appears likely to succeed.
During the second half of this conversation, panelists share their common hope that this data will be sufficient to get OCA approved and discuss what this could mean for the entire Fatty Liver stakeholder community.
Back in March 2023, Jeff McIntyre (GLI) introduced a draft report from the Institute for Clinical and Economic Review (ICER) on resmetirom and obeticholic acid for NASH. The Surfers dedicated an episode to expand on the contents, its shortcomings and potential implications with special guests Veronica Miller (Liver Forum) and Hannah Mamuszka (Alva10). This week, SurfingNASHrevisits the topic after a public comments session took place last week. In doing so, patient advocates and friends of the podcast Mike Betel (Fatty Liver Alliance), Tony Villiotti (NASHkNOWledge) and Wayne Eskridge (Fatty Liver Foundation) join co-hosts Louise Campbell and Roger Green to share a range of impressions.
This final conversation focuses on the most important thing each panelist would like ICER to learn before another NASH drug analysis. In our first conversation with Jeff McIntyre, he said that it while it was appreciated that patients have a voice, it's not the same as having a vote. The patient advocate comments in this conversation make it clear exactly how wide the gap between the two is right now. Fortunately, as Veronica miller noted during that preceding episode, ICER reporting has no impact on FDA decisions. However, as we discuss during this conversation, it might have an impact on payers.
If you enjoy the episode, have questions or interest around endocrinology and Fatty Liver disease, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
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Back in March 2023, Jeff McIntyre (GLI) introduced a draft report from the Institute for Clinical and Economic Review (ICER) on resmetirom and obeticholic acid for NASH. The Surfers dedicated an episode to expand on the contents, its shortcomings and potential implications with special guests Veronica Miller (Liver Forum) and Hannah Mamuszka (Alva10). This week, SurfingNASHrevisits the topic after a public comments session took place last week. In doing so, patient advocates and friends of the podcast Mike Betel (Fatty Liver Alliance), Tony Villiotti (NASHkNOWledge) and Wayne Eskridge (Fatty Liver Foundation) explain the why they chose to deliver their specific testimonies.
Mike shares a compelling anecdote around the ongoing challenges which persist in the post-recovery of NAFLD. Specifically, he suggests the document made light of bariatric surgery as a treatment option and failed to consider the extent of preparations and persistence which it requires. Wayne expands on his disappointment with the fact that the document does not consider NAFLD/NASH as a progressive disease. As a numbers guy, Tony explains that he chose to discuss the significant fallacies in the populations and numbers chosen for the economic analysis.
If you enjoy the episode, have questions or interest around endocrinology and Fatty Liver disease, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
In March 2023, Jeff McIntyre (GLI) introduced a draft report from the Institute for Clinical and Economic Review (ICER) on resmetirom and obeticholic acid for NASH. The Surfers dedicated an episode to expand on the contents, its shortcomings and potential implications with special guests Veronica Miller (Liver Forum) and Hannah Mamuszka (Alva10). SurfingNASH revisits the topic after a public comments session took place last week. In this review, patient advocates and friends of the podcast Mike Betel (Fatty Liver Alliance), Tony Villiotti (NASHkNOWledge) and Wayne Eskridge (Fatty Liver Foundation) join co-hosts Louise Campbell and Roger Green to share a range of impressions.
Roger begins this conversation with the note that if the cost of biopsy is factored into the cost of diagnosing a patient, the cost of diagnosis will be absurd. The group goes on to more extensively explore the role of biopsy in prescribing NASH therapeutics. From here, Wayne notes the idea that lifestyle adjustments take time and can be tremendously difficult. Considering this, he asserts it would be incredibly valuable if there were a therapeutic option that at least halted progression which in turn provides the time to successfully see through lifestyle interventions. Roger relates this perspective to how we consider trial endpoints. Ultimately, Louise states the recurring idea that while not every patient is symptomatic, we know this is a progressive disease that doesn’t necessarily fit the sort of spectrum detailed by ICER. Towards the end of the episode, Mike notes that the public comments session was rather liver-centric and siloed from more holistic metabolic thinking.
If you enjoy the episode, have questions or interest around endocrinology and Fatty Liver disease, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
In March 2023, Jeff McIntyre (GLI) introduced a draft report from the Institute for Clinical and Economic Review (ICER) on resmetirom and obeticholic acid for NASH. The Surfers dedicated an episode to expand on the contents, its shortcomings and potential implications with special guests Veronica Miller (Liver Forum) and Hannah Mamuszka (Alva10). This week, SurfingNASH revisits the topic after a public comments session took place last week. In this review, patient advocates and friends of the podcast Mike Betel (Fatty Liver Alliance), Tony Villiotti (NASHkNOWledge) and Wayne Eskridge (Fatty Liver Foundation) join co-hosts Louise Campbell and Roger Green to share a range of impressions.
In this conversation, Roger asks the group how the word empathy fits into the discussion. Tony shares that he was upset by the majority viewpoint of 15 featured voting members. Specifically, 40% of these voting members suggested that a drug approval would have no impact on a caregiver’s life. Tony asserts the importance for people to be aware of the impact of NAFLD/NASH not only on the patient, but also the families and others close to them. Speaking from personal experience, Wayne shares that he was perplexed on the position that this was not considered a progressive disease. This leads Louise and Roger to insert comments around the pricing and economic analysis surrounding the discussion. As the conversation winds down, Mike returns to the conundrum of the voting results. Listen on to hear why his reaction was, “I literally fell out of my chair.”
If you enjoy the episode, have questions or interest around endocrinology and Fatty Liver disease, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
In March 2023, Jeff McIntyre (GLI) introduced a draft report from the Institute for Clinical and Economic Review (ICER) on resmetirom and obeticholic acid for NASH. The Surfers dedicated an episode to expand on the contents, its shortcomings and potential implications with special guests Veronica Miller (Liver Forum) and Hannah Mamuszka (Alva10). This week, SurfingNASH revisits the topic after a public comments session took place last week. In this review, patient advocates and friends of the podcast Mike Betel (Fatty Liver Alliance), Tony Villiotti (NASHkNOWledge) and Wayne Eskridge (Fatty Liver Foundation) join co-hosts Louise Campbell and Roger Green to share a range of impressions.
Roger leads this conversation by asking the panelists how each came to give commentary and be involved in this process. Both Wayne and Tony disclose that they have previously worked with ICER through different interviews and seamlessly discovered the opportunity to speak on this occasion as a patient advocate. Wayne subsequently invited Mike to deliver a testimony as well. Next, Roger provides a soft introduction for the group to consider their feelings about the document and why each chose to comment on the items in which they noted in their testimonies. Similar to the reactions of our first episode on the Draft Report, it immediately becomes clear that the patient advocates also hold reservations about a number of aspects in this document. Tony adds a positive note around ICER’s willingness to engage with the patient advocate community on a certain level.
If you enjoy the episode, have questions or interest around endocrinology and Fatty Liver disease, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
Back in March 2023, Jeff McIntyre (GLI) introduced a draft report from the Institute for Clinical and Economic Review (ICER) on resmetirom and obeticholic acid for NASH. The Surfers dedicated an episode to expand on the contents, its shortcomings and potential implications with special guests Veronica Miller (Liver Forum) and Hannah Mamuszka (Alva10). This week, SurfingNASHrevisits the topic after a public comments session took place last week. In doing so, patient advocates and friends of the podcast Mike Betel (Fatty Liver Alliance), Tony Villiotti (NASHkNOWledge) and Wayne Eskridge (Fatty Liver Foundation) join co-hosts Louise Campbell and Roger Green to share a range of impressions.
00:00 Introduction05:28 How did each come to give commentary and be involved in the events of last Friday?09:46 Reactions to the word 'empathy' in regards to the discussion17:58 The role of biopsy and economics of diagnosing patients25:19 What motivated each patient advocate to deliver the testimonies which they specifically chose to34:00 The role of ICER , the FDA and final thoughtsSurf on to the full feature to capture the full extent of the insightful discourse. If you enjoy the episode, have questions or interest around endocrinology and Fatty Liver disease, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
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The paper “Clinical Care Pathway for the Risk Stratification and Management of Patients with Nonalcoholic Fatty Liver Disease” is a clarion call to action, but what exactly should clinicians do? This conversation From the Vault addresses that issue. Louise Campbell starts by stating that the World Health Organization should incorporate Fatty Liver disease into their diabetes initiative. Next, she leads the group into a discussion of the merits of transient elastography, which leads Ken Cusi and Stephen Harrison to discuss blood-based and imaging options clinicians can deploy when they lack access to a FibroScan or similar device. Finally, Roger asks the most important step stakeholders should take now, which provide an array of different actions.
As part of our ongoing dialogue around clinical care pathways and the complex of metabolic diseases, SurfingNASH dedicates a session to focus on the key relationship and interplay between endocrinology and hepatology. This topic rings familiar in the Rising Tide series, our podcast for frontline education, where Ken Cusi often notes the need for endocrinologists to become comfortable diagnosing Fatty Liver disease (and prescribing pioglitazone) and for hepatologists to become more comfortable prescribing GLP-1s. To expand on these critical ideas with the SurfingNASH community, Jörn Schattenberg, Louise Campbell and Roger Green are joined by Cyrielle Caussy, Professor of Nutrition and Endocrinologist-Diabetologist at Lyon 1 University and Lyon South Hospital, Hospices Civils de Lyon (France). Cyrielle is an expert in the clinical care of metabolic disease, including type 2 diabetes, obesity and NAFLD, and she is leading a clinical and research program focused on metabolic liver disease at the Lyon Hepatology Institute.
This conversation begins with Jörn concurring with Cyrielle's statement about the importance of regular interaction and communication. Roger also agrees before asking Jörn for what he considers to be key in getting liver patients picked up earlier by endocrinologists, primary care or even gastroenterologists. Jörn replies that this specific health system pathway will matter, but the role of nurse practitioners will be the key. He also emphasizes the importance of offering better information to patients. Finally, he says we need to stress that there are things physicians can do with these patients and this will become easier to discuss once drugs have been approved. Louise notes that this aligns with her focus on the role of allied health providers. She goes on to comment on the value of VCTE in identifying disease in all kinds of different patients. Jörn adds that at least once a week he is asked to consult on a patient whose unrelated surgery led to a decompensating cirrhotic event. As the session winds down, Roger asks the panelists what they would do if they had a magic wand to touch one thing in their hospital to make a change. Listen on to hear their varying and surprising answers.
If you enjoy the episode, have questions or interest around endocrinology and Fatty Liver disease, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
As part of our ongoing dialogue around clinical care pathways and the complex of metabolic diseases, SurfingNASH dedicates a session to focus on the key relationship and interplay between endocrinology and hepatology. This topic rings familiar in the Rising Tide series, our podcast for frontline education, where Ken Cusi often notes the need for endocrinologists to become comfortable diagnosing Fatty Liver disease (and prescribing pioglitazone) and for hepatologists to become more comfortable prescribing GLP-1s. To expand on these critical ideas with the SurfingNASH community, Jörn Schattenberg, Louise Campbell and Roger Green are joined by Cyrielle Caussy, Professor of Nutrition and Endocrinologist-Diabetologist at Lyon 1 University and Lyon South Hospital, Hospices Civils de Lyon (France). Cyrielle is an expert in the clinical care of metabolic disease, including type 2 diabetes, obesity and NAFLD, and she is leading a clinical and research program focused on metabolic liver disease at the Lyon Hepatology Institute.
Louise leads this conversation with a question around designing a more comprehensive metabolic blood profile in light of the vastness of metabolic syndrome and diseases. Jörn responds that while a metabolic screening would be of strong research interest, the message discussed in this episode champions simplicity, practicality and the ability to empower physicians for the identification and risk stratification of their patient population. From here, Cyrielle describes discovering patients with NAFLD-driven diabetes and the implications that various subtypes have on disease prognosis.
Jörn takes an amusing turn to a recently published article in Nature which points to liver disease, viral hepatitis and alcohol consumption as causes of the composer Beethoven’s demise. Tune in to the full conversation to learn more about this unique case.
If you enjoy the episode, have questions or interest around endocrinology and Fatty Liver disease, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
As part of our ongoing dialogue around clinical care pathways and the complex of metabolic diseases, SurfingNASH dedicates a session to focus on the key relationship and interplay between endocrinology and hepatology. This topic rings familiar in the Rising Tide series, our podcast for frontline education, where Ken Cusi often notes the need for endocrinologists to become comfortable diagnosing Fatty Liver disease (and prescribing pioglitazone) and for hepatologists to become more comfortable prescribing GLP-1s. To expand on these critical ideas with the SurfingNASH community, Jörn Schattenberg, Louise Campbell and Roger Green are joined by Cyrielle Caussy, Professor of Nutrition and Endocrinologist-Diabetologist at Lyon 1 University and Lyon South Hospital, Hospices Civils de Lyon (France). Cyrielle is an expert in the clinical care of metabolic disease, including type 2 diabetes, obesity and NAFLD, and is leading a clinical and research program focused on metabolic liver disease at the Lyon Hepatology Institute.
This conversation starts with Louise’s question around how patients respond when informed of liver-related conditions in the endocrinology clinic setting. Cyrielle shares a positive anecdote where a patient with obesity and Type-2 diabetes ultimately managed to improve weight in striving for a healthier liver status. For many patients, the notion that improving liver health will holistically improve their overall condition is a powerful and resonating source of motivation. Jörn notes this sort of positive relationship around biofeedback to be a recurring subject on the podcast. From here, Louise steers conversation to consider Cyrielle’s Paris NASH presentation which investigates how different phenotypes for chronic kidney patients may imply elevated risk of NAFLD and NASH. After elaborating briefly on this note, Cyrielle concludes with a powerful takeaway: “classifying your patient based on the presence of NAFLD or not is also classifying your patient regarding the prognosis of diabetes and not only the prognosis of liver.” As the session winds down, Jörn adds fascinating thoughts around the mechanisms and relationship between staging of liver disease, fibrogenesis and the metabolic drive that concerns the kidneys in parallel.
If you enjoy the episode, have questions or interest around endocrinology and Fatty Liver disease, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
As part of our ongoing dialogue around clinical care pathways and the complex of metabolic diseases, SurfingNASH dedicates a session to focus on the key relationship and interplay between endocrinology and hepatology. This topic rings familiar in the Rising Tide series, our podcast for frontline education, where Ken Cusi often notes the need for endocrinologists to become comfortable diagnosing Fatty Liver disease (and prescribing pioglitazone) and for hepatologists to become more comfortable prescribing GLP-1s. To expand on these critical ideas with the SurfingNASH community, Jörn Schattenberg, Louise Campbell and Roger Green are joined by Cyrielle Caussy, Professor of Nutrition and Endocrinologist-Diabetologist at Lyon 1 University and Lyon South Hospital, Hospices Civils de Lyon (France). Cyrielle is an expert in the clinical care of metabolic disease, including type 2 diabetes, obesity and NAFLD, and is leading a clinical and research program focused on metabolic liver disease at the Lyon Hepatology Institute.
This conversation begins with Roger’s note that around 50% of all cirrhosis is diagnosed for the first time during a decompensation event at the emergency department. He asks whether the endocrinology clinic is the right place to identify patients much sooner. Jörn suggests the answer is yes considering that we know the risk and prevalence of advanced fibrosis in this population to be high. The group goes on to discuss requesting and receiving lab results in their respective different systems and how hitching a test, like FIB-4, to routine care protocols could be an effective route for implementation. Cyrielle suggests that “the most important thing is convincing the endocrinologists” of NAFLD/NASH prevalence and our concerted ability to identify disease and stop progression at their clinics. She goes on to highlight the building momentum and consensus of guidelines from a range of different fields and organizations that formally recognize the relevance of Fatty Liver and the adoption of FIB-4 as a simple and cheap frontline test. She points out that In the most recent wave of published guidelines, there is a notedly improved sense of clarity in recommendations around how to identify and respond to patients with NAFLD/NASH.
Roger raises the point that the US might be one of the only countries, if not the only, that includes ALT values on blood panels. He asks Cyrielle what the process looks like in France for requesting ALT values to which she describes a relatively simple set of protocols. Jörn next describes his experiences within the German system. As the conversation winds down, discussion focuses on patient management and the importance of risk stratification in identifying those with more severe progression of disease.
If you enjoy the episode, have questions or interest around endocrinology and Fatty Liver disease, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
As part of our ongoing dialogue around clinical care pathways and the complex of metabolic diseases, SurfingNASH dedicates a session to focus on the key relationship and interplay between endocrinology and hepatology. This topic rings familiar in the Rising Tide series, our podcast for frontline education, where Ken Cusi often notes the need for endocrinologists to become comfortable diagnosing Fatty Liver disease (and prescribing pioglitazone) and for hepatologists to become more comfortable prescribing GLP-1s. To expand on these critical ideas with the SurfingNASH community, Jörn Schattenberg, Louise Campbell and Roger Green are joined by Cyrielle Caussy, Professor of Nutrition and Endocrinologist-Diabetologist at Lyon 1 University and Lyon South Hospital, Hospices Civils de Lyon (France). Cyrielle is an expert in the clinical care of metabolic disease, including type 2 diabetes, obesity and NAFLD, and is leading a clinical and research program focused on metabolic liver disease at the Lyon Hepatology Institute.
New to the podcast, Cyrielle takes a moment to outline her career trajectory and how she became interested in Fatty Liver disease and its growing area of overlap within the wider scope of medical care. From here, Roger describes overarching questions that the episode aims to cover:
- What does the interaction between endocrinologists and hepatologists look like from their relative perspectives?
- In practical terms, how does each approach care pathways, referrals and collaboration?
- What about either speciality would be key for the other to learn more about, develop and integrate?
Jörn first comments on the value of deploying the NITs developed by the hepatology community to endocrinology clinics. He notes the practical barriers which could hinder uptake and utilization as many may have lingering questions. How will this make a difference in the management of my patient? How do I potentially deal with a positive test? Do I need to refer this patient and what if I have nobody to refer to? Jörn looks to Cyrielle for advice on how to entice endocrinologists to align with the need of identifying Fatty Liver disease in their at-risk populations. Among other insights, Cyrielle underscores the importance behind raising awareness with endocrinologist colleagues that patients in routine screening are regularly diagnosed with advanced fibrosis and cirrhosis in the absence of symptoms.
If you enjoy the episode, have questions or interest around endocrinology and Fatty Liver disease, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
As part of our ongoing dialogue around clinical care pathways and the complex of metabolic diseases, SurfingNASH dedicates a session to focus on the key relationship and interplay between endocrinology and hepatology. This topic rings familiar in the Rising Tideseries, our podcast for frontline education, where Ken Cusi often notes the need for endocrinologists to become comfortable diagnosing Fatty Liver disease (and prescribing pioglitazone) and for hepatologists to become more comfortable prescribing GLP-1s. To expand on these critical ideas with the SurfingNASH community, Jörn Schattenberg, Louise Campbell and Roger Green are joined by Cyrielle Caussy, Professor of Nutrition and Endocrinologist-Diabetologist at Lyon 1 University and Lyon South Hospital, Hospices Civils de Lyon (France). Cyrielle is an expert in the clinical care of metabolic disease, including type 2 diabetes, obesity and NAFLD, and she is leading a clinical and research program focused on metabolic liver disease at the Lyon Hepatology Institute.
02:14 Introducing Cyrielle Caussy and Her Professional BackgroundNew to the podcast, Cyrielle takes a moment to outline her career trajectory and how she became interested in Fatty Liver disease and its growing area of overlap within the wider scope of medical care.
08:42 Educating Endocrinologists on the Power of NITs Developed in HepatologyFrom here, Roger describes overarching questions that the episode aims to cover:
- What does the interaction between endocrinologists and hepatologists look like from their relative perspectives?
- In practical terms, how does each approach care pathways, referrals and collaboration?
- What about either speciality would be key for the other to learn more about, develop and integrate?
Jörn comments on the value of deploying the NITs developed by the hepatology community to endocrinology clinics. He notes the practical barriers which could hinder uptake and utilization. Among other insights, Cyrielle underscores the importance behind raising awareness among our endocrinology colleagues that patients in routine screening are regularly diagnosed with advanced fibrosis and cirrhosis in the absence of symptoms.
14:32 The Importance of Early Identification in At-Risk Populations and Implementing Guidelines
Roger notes that around 50% of all cirrhosis is diagnosed for the first time during a decompensation event at the emergency department. He asks whether the endocrinology clinic is the right place to identify patients much sooner. Jörn suggests the answer is yes considering that we know the risk and prevalence of advanced fibrosis in this population to be high. The group goes on to discuss requesting and receiving lab results in their respective different systems.
25:55 Discussing the Patient Perspective in Endocrinology ClinicsLouise asks how do patients respond when informed of fibrosis or other liver related conditions in the endocrinology clinic setting.
33:40 Biomarkers, Holistic Metabolic Assessment and PathwaysThe groups discusses takeaways from various studies on the interrelatedness of concurrent metabolic conditions and the influence of liver health.40:57 Calling All Parties to Invest in Fighting Fatty LiverIf you enjoy the episode, have questions or interest around endocrinology and Fatty Liver disease, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com.
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Surfing the NASH Tsunami celebrates its 3rd anniversary since the debut episode posted on April 15, 2020. The Big Band of Stephen Harrison, Jörn Schattenberg, Louise Campbell and Roger Green get together to reflect on key moments from the podcast’s history as well as predict milestones that will make the highlights in a 6th anniversary special three years into the future.
This final conversation starts with Roger recalling his forecasting roots. He agrees with Stephen that the more we learn about the role the liver plays in the constellation of metabolic disease and other causes of death, the more these diseases will fold back on themselves to create a richly textured understanding of how to treat the holistic patient at both the primary care and specialty level. This idea leads Louise to come back to one of her primary points throughout the podcast. She asserts that poor liver health is the problem and improving it early in life is pivotal. She goes as far as to describe the liver as the primary target for improving society's health and also to save money because improved health leads to lower demand for expensive medications and procedures.
The final question asks the group to consider what will be discussed on the sixth anniversary of Surfing the NASH Tsunami in 2026. Jörn discusses the increased use of treatment pathways. Stephen makes a statement he considers controversial, suggesting that only obeticholic acid and resmetirom will be approved by 2026. He goes on to discuss what this would mean in terms of care strategies and why advances in NITs will become even more important. As the session winds down, Roger asks Stephen to offer the last word of the day in which he replies, Promise. Tune in to the conversation for a special birthday surprise at the end.
If you enjoy the special, have questions or interest around Fatty Liver disease, please let us know your ideas by writing to questions@SurfingNASH.com and leaving a review wherever you download the discourse.
Stay Safe and Surf On!
Surfing the NASH Tsunami celebrates its 3rd anniversary since the debut episode posted on April 15, 2020. The Big Band of Stephen Harrison, Jörn Schattenberg, Louise Campbell and Roger Green get together to reflect on key moments from the podcast’s history as well as predict milestones that will make the highlights in a 6th anniversary special three years into the future.
This conversation begins with Louise's perspective on what has played out to be either expected or unexpected in the liver space over the last three years. While aligned with the preceding responses of Stephen and Jörn, Louise raises her disappointment with the absence of an OCA approval from the FDA. She notes her belief that this experience has an important and positive influence on today's drug development landscape. In example, Louise points to increasing patient participation in clinical trials and improvements in trial design as positive major events. She then shifts to discuss nurse and allied provider education as a critical area experiencing growth. Her emphasis is on driving this trend forward given that these frontline professionals will be pivotal providers in patient education support when therapies become available.
The group goes on to consider Roger's comments around how much richer collective knowledge has become over the time we've been doing this podcast. Roger also shares some favorite phrases of the co-Surfers that emerged in the podcast Drinking Game. Later, Stephen comments on the importance of NASH drugs in the entire constellation of metabolic diseases as well as extrahepatic cancers and obesogenic cancers. Finally, Jörn suggests that treatment will start slowly when drugs are approved, and that we will learn over time how to most effectively use the available tools and therapies.
If you enjoy the special, have questions or interest around Fatty Liver disease, please let us know your ideas by writing to questions@SurfingNASH.com and leaving a review wherever you download the discourse.
Stay Safe and Surf On!
Surfing the NASH Tsunami celebrates its 3rd anniversary since the debut episode posted on April 15, 2020. The Big Band of Stephen Harrison, Jörn Schattenberg, Louise Campbell and Roger Green get together to reflect on key moments from the podcast’s history as well as predict milestones that will make the highlights in a 6th anniversary special three years into the future.
This conversation focuses more on the trajectory of liver science than on the podcast itself. Starting with Stephen, Roger asks what has played out in the last three years that would and would not have been expected. Stephen articulates a most cogent response to recap critical evolutions witnessed by the field over the past 36 months. Number one on this list is the “advancement of our understanding of the noninvasive technologies and the diagnostic algorithms that have reached alignment by multiple different societies.” This point leads to discussion of how he has come to think of the role of biopsy and comments around the development of cohesive guidance documents for diagnosing patients. An invaluable takeaway: “There is a roadmap to get people to therapy.” From here Stephen continues to elucidate on what’s happening in the biomarker field before expressing interest in what’s emerging from the developments of AI-assisted digital pathology. Lastly, Stephen underscores that a wealth of information is contributing to new targets for drug development trials. As the session winds down, Jörn highlights his excitement for both the acceleration of opportunities generated by drug companies and the ongoing strength in the role of academia.
If you enjoy the special, have questions or interest around Fatty Liver disease, please let us know your ideas by writing to questions@SurfingNASH.com and leaving a review wherever you download the discourse.
Stay Safe and Surf On!
Surfing the NASH Tsunami celebrates its 3rd anniversary since the debut episode posted on April 15, 2020. The Big Band of Stephen Harrison, Jörn Schattenberg, Louise Campbell and Roger Green get together to reflect on key moments from the podcast’s history as well as predict milestones that will make the highlights in a 6th anniversary special three years into the future.
This conversation features some amusing throwback clips to the first-time appearances of Stephen, Louise and Jörn on the podcast. Stephen notes that since his debut episode, more and more positive data continues to emerge from the field. Louise recalls her debut as rather impromptu and enticing from a nursing perspective. Jörn talks about how he discovered the podcast and eventually appeared as a guest. The group goes on to discuss a particularly exhilarating episode which demonstrated the “strongest emotion yet” on the podcast. Tune in to hear the full story.
If you enjoy the special, have questions or interest around Fatty Liver disease, please let us know your ideas by writing to questions@SurfingNASH.com and leaving a review wherever you download the discourse.
Stay Safe and Surf On!
Surfing the NASH Tsunami celebrates its 3rd anniversary since the debut episode posted on April 15, 2020. The Big Band of Stephen Harrison, Jörn Schattenberg, Louise Campbell and Roger Green get together to reflect on key moments from the podcast’s history as well as predict milestones that will make the highlights in a 6th anniversary special three years into the future.
This initial conversation begins by catching up with Stephen as he provides a crash-course on the myriad of activities that have kept him busy since last appearing on the podcast. He talks about working on improving the ways in which we enroll for clinical trials and addressing screen fail rates. Stephen goes on to describe “focusing diligently on efforts with digital pathology to bridge the gap between ordinal path reading and noninvasive testing reading.” He notes the ability of the various consortia in driving the paradigm forward on diagnosis, monitoring, response to therapy and predicting long term outcomes using noninvasive testing strategy.
Later on, Roger cues a throwback to the original Surfing NASH introduction which kicked off some of the earlier episodes. It’s evident that the program has come a long way not only in its production, but also in discourse as the field progresses with time. This leads the group to reminisce on some of the bolder moments in the podcast’s history.
If you enjoy the special, have questions or interest around Fatty Liver disease, please let us know your ideas by writing to questions@SurfingNASH.com and leaving a review wherever you download the discourse.
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This week, Surfing the NASH Tsunami celebrates its 3rd anniversary since the debut episode posted on April 15, 2020. We are offering a jam-packed special featuring individual interviews with guests Amy Articolo of Novo Nordisk, Donna Cryer of the Global Liver Institute, and Frédéric Cren of Inventiva Pharma.
In this final interview, Frédéric, Louise Campbell and Roger Green exchange ideas around, among other topics, the history and development of Inventiva’s lead product candidate, PPAR agonist lanifibranor.
If you enjoy the special, have questions or interest around Fatty Liver disease, please let us know your ideas by writing to questions@SurfingNASH.com and leaving a review wherever you download the discourse.
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This week, Surfing the NASH Tsunami celebrates its 3rd anniversary since the debut episode posted on April 15, 2020. We are offering a jam-packed special featuring individual interviews with guests Amy Articolo of Novo Nordisk, Donna Cryer of the Global Liver Institute, and Frédéric Cren of Inventiva Pharma.
In this conversation, Louise Campbell and Roger Green sit down with Donna to reflect on the last three years in NASH-ville and predict what the next three will look like. Among other notes, Donna describes the ongoing process of activating all within the NASH community to fight fatty liver disease.
If you enjoy the special, have questions or interest around Fatty Liver disease, please let us know your ideas by writing to questions@SurfingNASH.com and leaving a review wherever you download the discourse.
Stay Safe and Surf On!
This week, Surfing the NASH Tsunami celebrates its 3rd anniversary since the debut episode posted on April 15, 2020. We are offering a jam-packed special featuring individual interviews with guests Amy Articolo of Novo Nordisk, Donna Cryer of the Global Liver Institute, and Frédéric Cren of Inventiva Pharma.
In this conversation with Amy, Louise Campbell and Roger Green, the group reflects on the last three years in NASH-ville and predict what the next three will look like. Amy discusses ‘ah-ha’ moments, the power of collaboration, clinical care pathways and the therapeutic trajectory of fighting fatty liver disease.
If you enjoy the special, have questions or interest around Fatty Liver disease, please let us know your ideas by writing to questions@SurfingNASH.com and leaving a review wherever you download the discourse.
Stay Safe and Surf On!
This week, Surfing the NASH Tsunami celebrates its 3rd anniversary since the debut episode posted on April 15, 2020. In doing so, we are offering a jam-packed special featuring commentary from the original Big Band of Stephen Harrison, Jörn Schattenberg and Roger Green. The second leg of the special features individual interviews with special guests Amy Articolo of Novo Nordisk, Donna Cryer of the Global Liver Institute, and Frédéric Cren of Inventiva Pharma.
These conversations traverse reflections from the last three years in NASH-ville and predict what the next three will look like. Plus, listeners also can enjoy throwbacks to key moments in the podcast's history of when we met our beloved Surfers.
0:00 Introduction to the Surfing NASH 3rd Anniversary Special
2:31 Co-Surfer Roundtable: Revisiting Highlights from 3 Years on the Podcast
2:48 Catching Up with Stephen Harrison
8:28 How It All Started
13:24 Throwback to Meeting Stephen Harrison
16:02 Throwback to Meeting Louise Campbell
18:34 Throwback to Meeting Jörn Schattenberg
21:32 Strongest Emotion Recorded on the Podcast
22:39 Throwback to Meeting Donna Cryer
24:42 The Expected vs the Unexpected Over 3 Years in the Fatty Liver Space
39:45 The Straightjacket of Biopsy
45:30 Canary in the Coal Mine
48:06 Predictions for the Surfing NASH 6th Anniversary
58:35 Interview with Amy Articolo of Novo Nordisk
1:12:43 Interview with Donna Cryer of the Global Liver Institute
1:28:11 Interview with Frédéric Cren of Inventiva Pharma
1:40:30 Business Report
If you enjoy the special, have questions or interest around Fatty Liver disease, please let us know your ideas by writing to questions@SurfingNASH.com and leaving a review wherever you download the discourse.
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Thursday, June 9, 2022 was the 5th International NASH Day (#NASHDay). Global Liver Institute, the largest liver patient advocacy organization in the world, and 200 partner organizations held a day of education, awareness and motivation for Fatty Liver stakeholders across the globe.
For its wrap-up panel, GLI invited the SurfingNASH co-host team to sit with Jeff McIntyre and review some of the day’s major themes as well as major developments since the last International NASH Day. Like a typical SurfingNASH episode, there were equal parts big-picture thinking, references to recent events, and laughs. Listen for a fast-paced discussion of big-picture items, most of which are different from the Episode 28 discussion.
As International #NASHDay 2023 approaches on June 8th, Surfing NASH dedicates a session to explore what makes this year’s occasion incredibly important for patient advocacy and what we all can consider in preparation. Founder, President and Chief Executive Officer of the Global Liver Institute (GLI), Donna Cryer, shares her anticipations alongside Pamela Danagher (Terns Pharmaceuticals) and co-hosts Jörn Schattenberg and Roger Green.
In this final session, Donna has departed and the remaining panelists propose ways by which to we can “step up” for this year’s #NASHDay. Jörn notes the benefit of early planning to prepare promotion and engagement within his own clinic and the various professional societies. Roger suggests obesity to be an intertwined area of focus important to include in #NASHDay activities. From an industry perspective, Pam is interested in working with the assistance and collaboration of regulatory authorities to create drug development pathways that are simpler, faster, less invasive and minimize the need for any unnecessary biopsies. Roger states that the way we envision the future is limited by biopsy in terms of the definition of what efficacy is and how to conduct clinical trials. For him, a big step up for all is to adopt a bold and expansive view of how the world is going to change and to anticipate with proactivity.
If you enjoy the episode, have questions or interest around its contents and Fatty Liver disease, we kindly ask that you submit reviews wherever you download our discussions. Further, if you have questions or interest around participating in #NASHDay 2023, please let us know your ideas by writing to questions@SurfingNASH.com.
Stay Safe and Surf On!
As International #NASHDay 2023 approaches on June 8th, Surfing NASH dedicates a session to explore what makes this year’s occasion incredibly important for patient advocacy and what we all can consider in preparation. Founder, President and Chief Executive Officer of the Global Liver Institute (GLI), Donna Cryer, shares her anticipations alongside Pamela Danagher (Terns Pharmaceuticals) and co-hosts Jörn Schattenberg and Roger Green.
The group considers what activating awareness looks like in different community settings. Donna notes the opportunity for larger companies to be involved in educating employees on liver health. To assist in landing these opportunities, GLI is creating toolkits and presentations to educate and engage employees. Jörn adds that simple engagement with family members is also a critical opportunity for advocacy as we know there are higher rates of incidence in fatty liver disease for those sharing common genetics, diets and environments. Pamela raises the role of noninvasive technologies in screening/diagnosing patients and developing robust trial entry pathways. This prompts Donna to express her interest in facilitating mobile FibroScan clinics. Roger points out that should there be a NASH drug approval, more attention and energy will be dedicated to educating and treating fatty liver. As ideas continue to flow, it is eventually noted that fatty liver disease could benefit from having a celebrity patient advocate. One such celebrity who is already stepping up to NASH is baseball player and musician, Bernie Williams.
If you enjoy the episode, have questions or interest around its contents and Fatty Liver disease, we kindly ask that you submit reviews wherever you download our discussions. Further, if you have questions or interest around participating in #NASHDay 2023, please let us know your ideas by writing to questions@SurfingNASH.com.
Stay Safe and Surf On!
As International #NASHDay 2023 approaches on June 8th, Surfing NASH dedicates a session to explore what makes this year’s occasion incredibly important for patient advocacy and what we all can consider in preparation. Founder, President and Chief Executive Officer of the Global Liver Institute (GLI), Donna Cryer, shares her anticipations alongside Pamela Danagher (Terns Pharmaceuticals) and co-hosts Jörn Schattenberg and Roger Green.
This session starts with Roger asking Donna to point to one thing that happened in 2022 that had ripples in the pond of liver disease. He also wonders what will stimulate folks to think about what to do this year in terms of having an effect on 2024. Donna highlights distributing over $100,000 in community grants to support organizations in hosting events around the world for NASH education and advocacy. This investment has since led to strengthening partnerships and programs to promote liver health in places like Africa and India. One such activity that has seen an explosion in energy as a result of these partnerships is NASH clinical trial recruitment. For example, a San Diego chapter of GLI’s Liver Action Network identified 26 patients in a single day at one of their events. Donna and her team are digging deep to learn what worked so well that day and how to replicate results like this in the future. Pamela emphasizes the utility of strong clinical trial recruitment for continued drug development in a post-approval environment. Donna speaks to the need of connecting and diversifying the networks of care providers so that patients have referral access to endocrinologists in addition to hepatologists and gastroenterologists. Jörn underscores the untapped potential of the liver community in its ability to enable patients to take control of their liver conditions.
If you enjoy the episode, have questions or interest around its contents and Fatty Liver disease, we kindly ask that you submit reviews wherever you download our discussions. Further, if you have questions or interest around participating in #NASHDay 2023, please let us know your ideas by writing to questions@SurfingNASH.com.
Stay Safe and Surf On!
As International #NASHDay 2023 approaches on June 8th, Surfing NASH dedicates a session to explore what makes this year’s occasion incredibly important for patient advocacy and what we all can consider in preparation. Founder, President and Chief Executive Officer of the Global Liver Institute (GLI), Donna Cryer, shares her anticipations alongside Pamela Danagher (Terns Pharmaceuticals) and co-hosts Jörn Schattenberg and Roger Green.
Roger turns to Jörn and Pamela for their first impressions on what #NASHDay 2023 means to them. Jörn recalls his participation in the inaugural launch of #NASHDay in 2018, highlighting the unique and intimate qualities which characterize the campaign as community-centered. Donna shares an amusing anecdote of the support of a fellow Surfer, Manal Abdelmalek, before disclosing this year’s theme: Step Up to NASH. The group goes on to envision ways by which this theme of Step Up to NASH can manifest. Whether introducing institutions to GLI’s NASH Action Plan or organizing community climbs of iconic steps around the world, the goal is to engage and empower. Finally, Pamela adds her thoughts around what about having therapeutic approval will be a watershed moment for NASH in terms of leading the field into further developments.
If you enjoy the episode, have questions or interest around its contents and Fatty Liver disease, we kindly ask that you submit reviews wherever you download our discussions. Further, if you have questions or interest around participating in #NASHDay 2023, please let us know your ideas by writing to questions@SurfingNASH.com.
Stay Safe and Surf On!
As International #NASHDay 2023 approaches on June 8th, Surfing NASH dedicates a session to explore what makes this year’s occasion incredibly important for patient advocacy and what we all can consider in preparation. Founder, President and Chief Executive Officer of the Global Liver Institute (GLI), Donna Cryer, shares her anticipations alongside Pamela Danagher (Terns Pharmaceuticals) and co-hosts Jörn Schattenberg and Roger Green.
This conversation begins with Roger’s comment that 2023 is a critically important year for fatty liver disease and therefore sets the stage for a critically important #NASHDay. He asks Donna to describe any elements that GLI has pinpointed as pivotal in the approach to #NASHDay 2023. Donna first acknowledges the goal of facilitating and catalyzing all stakeholders to discover what fatty liver disease and NASH means to them. Over the last six years, #NASHDay has greatly grown in outreach and its impact on combating fatty liver. She goes on to state that this #NASHDay is embedded in the context of a momentous series of activities. Among these activities could be the milestone of a first NASH drug approval. Such a watershed moment requires a tremendous push for patient advocacy, education and regulatory organization.
If you enjoy the episode, have questions or interest around its contents and Fatty Liver disease, we kindly ask that you submit reviews wherever you download our discussions. Further, if you have questions or interest around participating in #NASHDay 2023, please let us know your ideas by writing to questions@SurfingNASH.com.
Stay Safe and Surf On!
As International #NASHDay 2023 approaches on June 8th, Surfing NASHdedicates a session to explore what makes this year’s occasion incredibly important for patient advocacy and what we all can consider in preparation. Founder, President and CEO of the Global Liver Institute (GLI), Donna Cryer, shares her anticipations alongside Pamela Danagher (Terns Pharmaceuticals) and co-hosts Jörn Schattenberg and Roger Green.
04:43 This Year’s Theme: #StepUpToNASHDonna begins by acknowledging the goal of facilitating and catalyzing all stakeholders to discover what fatty liver disease and NASH means to them. She goes on to describe that this #NASHDay is embedded in the context of a momentous series of activities. Among these activities could be the milestone of a NASH drug approval, which requires a tremendous push for patient advocacy, education and regulatory organization. Jörn recalls his participation in the inaugural launch of #NASHDay in 2018, highlighting the unique and intimate qualities which characterize the campaign as community-centered.
20:05 The Untapped Potential of the Liver CommunityRoger asks Donna to point to one thing that happened in 2022 that had ripples in the pond of liver disease. He also wonders what will stimulate folks to think about what to do this year in terms of having an effect on the outlook and agenda of 2024. Donna highlights distributing over $100,000 in community grants to support organizations to host global events around NASH education and advocacy. The investments have since led to strengthening partnerships and programs to promote liver health in places like Africa and India. One such partnering activity that has seen an explosion in energy is NASH clinical trial recruitment. Pam emphasizes the utility behind strong clinical trial recruitment for continued drug development in a post-approval environment.
27:54 Activating Awareness Across CommunitiesThe group considers what activating awareness looks like in different community settings. Donna notes the opportunity for larger companies to be involved in educating their employees on liver health. Jörn notes that simple communication within families is critical because we know there are higher rates of incidence in fatty liver disease for those sharing common genetics, diets and environments. Pam discusses the role of noninvasive technologies in screening/diagnosing patients and developing robust and accessible trial entry points. This prompts Donna to express interest in conducting mobile FibroScan clinics. As ideas continue to flow, it is also noted that fatty liver disease could benefit from having a celebrity patient advocate. Donna shouts out to baseball player and musician, Bernie Williams, for lending his voice to awareness around liver health.
37:09 "It Takes a Village"As the session winds down, each panelists proposes a few additional “step ups” to consider for this year’s #NASHDay. Jörn looks to plan early at his own clinic in addition to engaging the professional societies. Roger suggests obesity to be an intertwined area of focus for collaboration. From an industry perspective, Pam is interested in improving regulatory and drug development through opportunities to streamline or simplify their various processes. Finally, Donna departs and the remaining three panelists share final thoughts around what they look forward to in this year's day dedicated to fighting Fatty Liver.
If you enjoy the episode, have questions or interest around participating in #NASHDay 2023, please let us know your ideas by writing to questions@SurfingNASH.com.
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This week on Surfing NASH, co-hosts Jörn Schattenberg and Roger Green review the recently concluded Liver Forum. Joining discussion are Liver Forum Executive Director Veronica Miller and speakers Mazen Noureddin (Houston Research Institute), Michelle Long (Novo Nordisk) and Jeff McIntyre (Global Liver Institute).
This conversation From the Vault begins with Quentin Anstee complimenting Stephen Harrison for his observation that when we analyze NASH biomarkers, we should consider the value of sustained response separate from early OR late response.
From here, the group moves to the concept of “stacked” tests — confirmatory results from different NITs as a way to assess efficacy in an individual clinical trial subject. The conversation takes some twists and turns, but the core concept is unique, challenging and a significant step forward in the broader discussion of how to analyze biomarkers.
If you enjoy the episode, have questions or interest around its contents and Fatty Liver disease, we kindly ask that you submit reviews wherever you download our discussions. Alternatively, you can write to us directly at questions@SurfingNASH.com. Stay Safe and Surf On!
This week on Surfing NASH, co-hosts Jörn Schattenberg and Roger Green review the recently concluded Liver Forum. Joining discussion are Liver Forum Executive Director Veronica Miller and speakers Mazen Noureddin (Houston Research Institute), Michelle Long (Novo Nordisk) and Jeff McIntyre (Global Liver Institute).
In this final conversation, Roger prompts the group to share additional takeaways from the meeting that they feel would be valuable for the audience to review in the published slides. Michelle shares that the meeting strongly made clear the importance of collaborative thought and grappling with different perspectives while guided by patient needs. Jeff states that while it’s easy for the community to become self-congratulatory on the precipice of a first drug approval, he saw how approvals will morph and magnify challenges, particularly in terms of clinical trials going forward. Roger highlights how the meeting reframed for him the narrative around patient journey. Lastly, Veronica voices her appreciation for all forms of feedback which will help the Forum “push the science, push the thinking, and push the innovation to make things happen.”
If you enjoy the episode, have questions or interest around its contents and Fatty Liver disease, we kindly ask that you submit reviews wherever you download our discussions. Alternatively, you can write to us directly at questions@SurfingNASH.com. Stay Safe and Surf On!
This week on Surfing NASH, co-hosts Jörn Schattenberg and Roger Green review the recently concluded Liver Forum. Joining discussion are Liver Forum Executive Director Veronica Miller and speakers Mazen Noureddin (Houston Research Institute), Michelle Long (Novo Nordisk) and Jeff McIntyre (Global Liver Institute).
In this conversation, Veronica describes a session dedicated to statistics and being impressed with how well it played out as a morning opener. In agreement, Roger and Jeff share different perspectives as to how this session succeeded. Jeff suggests that while statistics can be daunting to patient groups, the presentations were cunningly communicated in a clear and approachable manner. Scott Evans of George Washington University opened with his talk, Desirability of Outcome Ranking (DOOR) Analysis. Lauren Dang of UC Berkeley followed with Hybrid Randomized/Real-World Data Designs: A Case Study of Semaglutide and Cardiovascular Outcomes. Veronica notes the benefit of harnessing data from different sources to inform how the field conducts clinical trials. She reasons that ultimately, “we don't want patients on placebo.” For a more detailed look into the discourse, the Liver Forum 14 slides are available for review on their website.
If you enjoy the episode, have questions or interest around its contents and Fatty Liver disease, we kindly ask that you submit reviews wherever you download our discussions. Alternatively, you can write to us directly at questions@SurfingNASH.com. Stay Safe and Surf On!
This week on Surfing NASH, co-hosts Jörn Schattenberg and Roger Green review the recently concluded Liver Forum. Joining discussion are Liver Forum Executive Director Veronica Miller and speakers Mazen Noureddin (Houston Research Institute), Michelle Long (Novo Nordisk) and Jeff McIntyre (Global Liver Institute).
Roger leads this conversation by asking the panelists to pick a particular session that captured their attention in a way that could not have been predicted. Michelle first mentions how the agenda as a whole illuminated the depth of the issues surrounding drug development for the fatty liver field. Veronica points to an interactive session titled NASH Drug Development in the Era of Approved Drugs, commending friends of the podcast Manal Abdelmalek and Pamela Danagher for their brilliant moderation. She says that hosting an unscripted panel in a safe environment with engaged participants is a way to “push the envelope and move the field forward.” Jörn notes data presented from the European Heart Journal as an exciting example of exploring and utilizing literature from outside the liver field. At this point, Mazen offers a more tangible description of some content covered. He details general concepts behind a session on Cirrhosis Working Group Updates which included his presentation on Compensated Cirrhosis Risk Stratification. As the conversation winds down, Veronica reminds that the slides from the event are published on the Liver Forum website and well worth a review.
If you enjoy the episode, have questions or interest around its contents and Fatty Liver disease, we kindly ask that you submit reviews wherever you download our discussions. Alternatively, you can write to us directly at questions@SurfingNASH.com. Stay Safe and Surf On!
This week on Surfing NASH, co-hosts Jörn Schattenberg and Roger Green review the recently concluded Liver Forum. Joining discussion are Liver Forum Executive Director Veronica Miller and speakers Mazen Noureddin (Houston Research Institute), Michelle Long (Novo Nordisk) and Jeff McIntyre (Global Liver Institute). Veronica leads this conversation with a recap of how the Forum aims to advance the regulatory sciences for the treatment of NAFLD/NASH and liver fibrosis by providing an independent and neutral venue for multi-stakeholder dialogue. She underscores the importance of being able to convene as a community to discuss how drugs get researched and approved, and how patients participate in this ongoing process. Jeff notes that patient involvement has increased with each successive year and points to a panel discussion following a presentation on OCA Program Learnings that featured a patient representative. Veronica later comments on the Forum’s history of representing patient voices at both an organization and individual level. Michelle reminds that “at the end of the day, it's about making people feel, function and survive better.” From the patient perspective, halting progression and stabilizing disease are significant quality of life components for treating NASH. Jörn agrees that this message around stabilization of disease can be better amplified before describing how the energies of the meeting carried through to Europe where he was attending remotely. Roger, who also attended remotely, comments positively on the cohesiveness of the program. Finally, Mazen introduces a few of the specific scientific topics explored. Namely, he touches on cirrhosis, the future of combination therapy, clinical trial design and a session on statistics which proved entertaining with charismatic presenters.
If you enjoy the episode, have questions or interest around its contents and Fatty Liver disease, we kindly ask that you submit reviews wherever you download our discussions. Alternatively, you can write to us directly at questions@SurfingNASH.com. Stay Safe and Surf On!
This week on Surfing NASH, co-hosts Jörn Schattenberg and Roger Green review the recently concluded Liver Forum. Joining discussion are Liver Forum Executive Director Veronica Miller and speakers Mazen Noureddin (Houston Research Institute), Michelle Long (Novo Nordisk) and Jeff McIntyre (Global Liver Institute). This integrative meeting aims to advance the regulatory sciences for the treatment of NAFLD/NASH and liver fibrosis by providing an independent and neutral venue for ongoing multi-stakeholder dialogue. The resulting conversations facilitate making the best science-based decisions on how to study efficacy and safety in real time as collective knowledge and experience with therapies for liver diseases develops. This year’s meeting proved particularly stimulating in light of imminent drug approvals.
What is The Liver Forum and First Impressions from The MeetingVeronica underscores the importance of being able to convene as a community to make advances in how drugs get researched and approved, and how patients participate in this ongoing process. Jeff notes benefits around increasing patient involvement in multiple panels with each successive year. Michelle reminds that “at the end of the day, it's about making people feel, function and survive better.” She notes that from the patient perspective, halting progression and stabilizing disease are significant quality of life components for treating NASH - a message which could see more amplification. Jörn describes how the energies of the meeting carried through to Europe where he was participating remotely. Roger, who also attended remotely, comments positively on the cohesiveness of the program. Finally, Mazen introduces specific topics explored, namely cirrhosis, the future of combination therapy and clinical trial design.
Panelists Select Sessions of InterestEach share takeaways around specific sessions that captured their attention in a way that could not have been predicted. Michelle mentions how the agenda as a whole illuminated the depth of the issues surrounding drug development for the fatty liver field. Veronica points to an interactive session titled NASH Drug Development in the Era of Approved Drugs, commending the moderators and friends of the podcast Manal Abdelmalek and Pamela Danagher. She says that hosting an unscripted panel in a safe environment with brilliant participants is a way to “push the envelope and move the field forward.” Jörn notes data presented from the European Heart Journal as an exciting example of exploring and utilizing literature from outside the liver field. Mazen elaborates on scientific concepts distilled from a session on cirrhosis.
Session VIII: Stretch Exercise: New Look at StatisticsVeronica describes a session dedicated to statistics and being impressed with how well it played out. In agreement, both Roger and Jeff share different perspectives as to how the session succeeded. Scott Evans of George Washington University opened with Desirability of Outcome Ranking (DOOR) Analysis. Lauren Dang of UC Berkeley followed with her talk, Hybrid Randomized/Real-World Data Designs: A Case Study of Semaglutide and Cardiovascular Outcomes.
Closing CommentsAs the session winds down, the group describes takeaways that might appear in the soon-to-be published slides. If you enjoy the episode, have questions or interest around the Liver Forum and Fatty Liver disease, we kindly ask that you submit reviews wherever you download our discussions. Alternatively, you can write to us directly at questions@SurfingNASH.com.
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This week on Surfing the NASH Tsunami, we are offering a co-host ‘roundtable’ catch-up between Jörn Schattenberg, Louise Campbell and Roger Green. This is a fun, casual conversation that looks into first quarter highlights and a preview of what’s to come in quarter two of 2023.
Roger begins this session by describing some of his anticipations around drug development in the second quarter, specifically pointing to emerging news on OCA and resmetirom. He also notes the possibility of new Phase 3 press releases on the horizon. Louise comments that with expected drug approvals, there needs to be more emphasis around allied health education, training and pathways. This leads Roger to share his belief that an approval in the US will lead to rather aggressive allied health education.
If you enjoy the episode, have questions or interest around its contents and Fatty Liver disease, we kindly ask that you submit reviews wherever you download our discussions. Alternatively, you can write to us directly at questions@SurfingNASH.com. Stay Safe and Surf On!
This week on Surfing the NASH Tsunami, we are offering a co-host ‘roundtable’ catch-up between Jörn Schattenberg, Louise Campbell and Roger Green. This is a fun, casual conversation that looks into first quarter highlights and a preview of what’s to come in quarter two of 2023.
Roger opens this final conversation by noting his growing enthusiasm for International NASH Day 2023. This leads Jörn to share interesting anecdotes to describe how different cultures face different health threats. For example, in Germany he questions whether he should be revisiting his position on recommendations around alcohol consumption. As the session winds down, Roger alludes to exciting plans for a Surfing NASH 4th anniversary special. The recording will take place on April 17th and we kindly invite those who are interested to participate as a live audience. For a final question, the Surfers visit what each thinks will be big ticket items for the second half of 2023 in the liver space. Louise looks to more education to bolster early detection. Jörn extends this thought to include the need for a clinical trial showing superiority of screening versus no screening in the general population. Lastly, Roger speaks to his contrasting interests around both the power of AI-assisted assessment of biopsy and the ability of consortia to demonstrate the effectiveness of NITs.
If you enjoy the episode, have questions or interest around its contents and Fatty Liver disease, we kindly ask that you submit reviews wherever you download our discussions. Alternatively, you can write to us directly at questions@SurfingNASH.com. Stay Safe and Surf On!
This week on Surfing the NASH Tsunami, we are offering a co-host ‘roundtable’ catch-up between Jörn Schattenberg, Louise Campbell and Roger Green. This is a fun, casual conversation that looks into first quarter highlights and a preview of what’s to come in quarter two of 2023.
In this conversation, each Surfer picks one thing that's anticipated to happen in the second quarter that they think is likely to be most momentous or compelling. Louise leads with comments around the rigorous approval process of NICE for primary care access to FibroScan in the UK. While extensive, these protocols produce world-leading cost-benefit analysis. The group goes on to discuss how different systems contribute to progress in the field through different qualities. Louise asserts that facilitating frontline screening will enable early detection and ultimately help prevent cirrhosis for many patients. As the conversation winds down, Jörn offers notes on the upcoming EASL Congress and Roger shares his latest metaphor to describe the dynamism of fighting fatty liver disease.
If you enjoy the episode, have questions or interest around its contents and Fatty Liver disease, we kindly ask that you submit reviews wherever you download our discussions. Alternatively, you can write to us directly at questions@SurfingNASH.com. Stay Safe and Surf On!
This week on Surfing the NASH Tsunami, we are offering a co-host ‘roundtable’ catch-up between Jörn Schattenberg, Louise Campbell and Roger Green. This is a fun, casual conversation that looks into first quarter highlights and a preview of what’s to come in quarter two of 2023.
In this conversation, Jörn recounts highlights from attending the 3rd Annual Liver Connect Conference organized by the Chronic Liver Disease Foundation. He enjoyed this meeting which encompassed the “latest and hottest on development” and being present for a powerful presentation by Scott Friedman. Scott shared interesting new concepts around ‘hot versus cold’ fibrosis states and how these influence drug development and the way we think of liver science. Roger points out that combination therapy may be the course of action when dealing with inflammation and fibrosis simultaneously.
If you enjoy the episode, have questions or interest around its contents and Fatty Liver disease, we kindly ask that you submit reviews wherever you download our discussions. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
This week on Surfing the NASH Tsunami, we are offering a co-host ‘roundtable’ catch-up between Jörn Schattenberg, Louise Campbell and Roger Green. This is a fun, casual conversation that looks into first quarter highlights and a preview of what’s to come in quarter two of 2023.
- Jörn recounts a productive trip to California where he attended the 3rd Annual Liver Connect Conference organized by the Chronic Liver Disease Foundation. He shares his highlights from the meeting, including a summary of a powerful presentation by Scott Friedman on ‘hot’ versus ‘cold’ fibrosis, cirrhosis, combination therapies and more.
- Louise speaks to the intensity involved in reviewing publication for FibroScan approval in primary care pathways in the UK. One benefit of the lengthy protocols that NICE considers is that it ultimately produces world-leading cost-benefit analysis. The group goes on to discuss how different systems contribute to the field through their different strengths.
- Roger uncovers a new metaphor for describing fatty liver disease and announces exciting plans for the podcast’s 4th anniversary special.
- Among a number of other insights emerging from this session, the Surfers also discuss what is happening in the space of drug development and impending approvals, the strength in allied health professionals and primary care pathways for fighting fatty liver.
If you enjoy the episode, have questions or interest around its contents and Fatty Liver disease, we kindly ask that you submit reviews wherever you download our discussions. Alternatively, you can write to us directly at questions@SurfingNASH.com.
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This episode From the Vault comes from the Surfing NASH coverage of the inaugural INCBCN Workshop, with Jörn Schattenberg serving as event co-founder and Louise Campbell and Roger Green moderating sessions. This episode is less a formal recap of the meeting than recollections of key moments and messages from the co-founders and Surfers.
This conversation wraps up the Surfers’ discussion of the conference. The co-hosts start with comments about pharma partners’ and patient advocates’ favorable reactions to the meeting and review many of the individual presentations. Louise shifts the focus of the conversation to the role of liver in overall metabolic wellness. Jörn notes that hepatologists are less likely to focus on liver fat as compared to fibrosis, and agrees that a broader focus on liver fat is important in the overall issue of metabolic health. The conversation ends with the group considering actions that might strengthen a successful 2022 conference when it recurs in 2023.
Surfing NASH returns to preview the second Innovations in NAFLD Care Workshop (INCBCN) to be held in Barcelona from 26-27 May, 2023. Conference founders and directors Jeff Lazarus and Jörn Schattenberg discuss what makes the event unique with Louise Campbell and Roger Green.
In this final conversation, Roger asks what sort of impact the Workshop will have. Specifically, he wonders what indicators in the next six months would be the signal of success. Jeff notes that last year’s meeting resulted in the publishing of an article in Nature’s new Open Access journal, Communications Medicine. Envisioning how the meeting plays out this year, Jeff believes it would be a great sign in November to have people asking to return and lining up funding for 2024. Roger next asks how an intimate meeting of this size will translate an impact into the broader population. Jeff suggests that by having KOL in attendance, they can take the experience back to their practices and share findings with colleagues. He emphasizes his hope that the impact will make its way out and that this is a meeting oriented to making change and not just publishing another abstract. “This is really about top line presentations coupled with exciting, engaged discussions.”
For the final question, Roger asks how the agenda will impact the next 12 months and what will grow to be a bigger focus for 2024. Surf on to find out.
If you enjoy the episode, have questions or interest around its contents and Fatty Liver disease, we kindly ask that you submit reviews wherever you download our discussions. Alternatively, you can write to us directly at questions@SurfingNASH.com.Stay Safe and Surf On!
Surfing NASH returns to preview the second Innovations in NAFLD Care Workshop (INCBCN) to be held in Barcelona from 26-27 May, 2023. Conference founders and directors Jeff Lazarus and Jörn Schattenberg discuss what makes the event unique with Louise Campbell and Roger Green.
Roger opens with a question around the involvement of non-physicians at the Workshop. Jeff again notes the presentations by esteemed nutritionist, Shira Zelber-Sagi, and epidemiologist, Harriet Rumgay. He also highlights patient organizations that have been reached out to for participation in a roundtable. Lastly, he says feedback will be welcomed to help strengthen the future of the program and its direction. Louise then shares her thoughts on participating in last year’s panel and injecting the strength of nursing perspectives.
From here, Roger asks what the panelists anticipate in the meeting that has yet to be covered. Jeff underscores the importance of facilitating interactive sessions that prompt engaged discussion and plenty of questions. Jörn states that this is not a lecture on drugs and basic science, but an opportunity to harness developments and empower practitioners and patients alike with energized talk around how to use it.
If you enjoy the episode, have questions or interest around its contents and Fatty Liver disease, we kindly ask that you submit reviews wherever you download our discussions. Alternatively, you can write to us directly at questions@SurfingNASH.com.
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Surfing NASH returns to preview the second Innovations in NAFLD Care Workshop (INCBCN) to be held in Barcelona from 26-27 May, 2023. Conference founders and directors Jeff Lazarus and Jörn Schattenberg discuss what makes the event unique with Louise Campbell and Roger Green. This conversation picks up with concluding comments around Day 1 in Barcelona. Jeff elaborates on a Patient Organisation session that closes with a roundtable discussion. For this discussion, Juan Mendive of the World Organization of Family Doctors will discuss primary care perspectives.
Moving into Day 2, Jeff shares that friends of the podcast Alina Allen and Mazen Noureddin will be opening with two exciting topics. Alina will be giving a presentation titled Automation, Artificial Intelligence and Machine Learning for Patient Identification and Risk Stratification. Following, Mazen will be detailing How to Overcome Barriers of Implementation - Bridging the Gap Between Science and Current Care Pathways. This opening session is chaired by Maru Rinella. Following is an industry session which will see a discussion featuring Peter Rydqvist (Madrigal Pharmaceuticals, Sweden) and Jeppe Zacho (Novo Nordisk, Denmark). Later and as part of a treatment and care session there will be an entertaining debate on whether being vegetarian offers a cure for NAFLD (led by Shira Zelber-Sagi and Camilla Dalby Hansen). This session also features a presentation by Stephen Harrison titled Medical Therapy in the Near Future. Stephen will also be joining Jeff in the final session to discuss Steven health equity in Fatty Liver disease and addressing disparities. Joining this session will be Zobair Younossi to discuss payer perspectives, Juan Pericàs on socioeconomics and Patrizia Carrieri on risks and interventions for women with NAFLD.
If you enjoy the episode, have questions or interest around its contents and Fatty Liver disease, we kindly ask that you submit reviews wherever you download our discussions. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
Surfing NASH returns to preview the second Innovations in NAFLD Care Workshop (INCBCN) to be held in Barcelona from 26-27 May, 2023. Conference founders and directors Jeff Lazarus and Jörn Schattenberg discuss what makes the event unique with Louise Campbell and Roger Green.
Jörn begins this conversation by noting the diverse, cross-disciplinary involvement of the event. He also shares details of an abstract he will be presenting on liver stiffness. Roger then returns to the idea of linking Fatty Liver and cancers. He recalls last week’s episode when Hannah Mamuszka noted the alarming degree to which all obesogenic cancers are related to Fatty Liver disease. Jeff notes the roundness of Day 1, citing the benefit of hosting a holistic discussion which features viewpoints on alcohol, diabetes and cancer. Jörn adds that by looking at the liver, we are empowering the patients and educating on their individual risk, ultimately informing in terms of cancer prevention. At this point, Louise expands on the importance of early screening in populations who are unaware of their liver health and the need to drive education for those at risk to know when and what to ask their providers. She notes the nonlinear progression to liver cancer, a recently recurring theme on the podcast. She then goes on to commend the convergence of fields, citing the various associations’ (including the American Heart Association and American Diabetes Association) growing inclusion of Fatty Liver in recommendations around risk assessment.
Roger connects the idea that endocrinologists are working in terms of cancer prevention. He reasons that if 70% of their patients have NAFLD, and if NAFLD elevates the risk of HCC, then “every time you treat a diabetic patient, you need to think about what you're doing in the context of avoiding cancer.” As the conversation winds down, Jörn mentions a pre-event on the opening morning called the NASH NITs Real World Evidence Summit, which lends to a more hands-on training around which biomarkers to use and implementation. Here, he explains, the experience aims to familiarize those who don't work with these tests everyday to gain the skills and confidence to effectively screen for Fatty Liver diseases.
If you enjoy the episode, have questions or interest around its contents and Fatty Liver disease, we kindly ask that you submit reviews wherever you download our discussions. Alternatively, you can write to us directly at questions@SurfingNASH.com.
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Surfing NASH returns to preview the second Innovations in NAFLD Care Workshop (INCBCN) to be held in Barcelona from 26-27 May, 2023. Conference founders and directors Jeff Lazarus and Jörn Schattenberg discuss what makes the event unique with Louise Campbell and Roger Green.
Roger leads this conversation with the note that for this year, Surfing NASH will be working closely with the conference to provide timely coverage from Barcelona. He then asks Jeff to elaborate on some of the feedback received from last year’s inaugural meeting. Immediately Jeff underscores that this meeting fills an important gap between the heavy-hitting conferences in NAFLD and NASH. Specifically, the INCBCN Workshop exists to explore dynamic and nuanced insights into both liver disease and holistic liver health in a smaller, more multidisciplinary forum. He recaps receiving positive feedback and what considerations are informing the follow-up program. It’s important to Jeff that leading KOLs in a range of disciplines from around the world have an opportunity to explore their ideas in an engaged setting. One of last year’s success indicators was that people stayed in the room, interacting from the moment of arrival in the morning through later in the evening. Jörn joins to note his enthusiasm around the practical component of this workshop in that it invests in ideas of implementation and engaging stakeholders beyond hepatology.
From here, Roger leads discussion into a breakdown of the Day 1 sessions. Jeff first expresses excitement for an opening talk by Ramon Bataller which considers alcohol intake alongside Fatty Liver diseases. This presentation focuses on the reality that many of those living with NAFLD and NASH do in fact consume alcohol. Jeff then points to the whole of Session 2 where Ken Cusi has organized a panel focusing on the challenges of Fatty Liver from a diabetes perspective. Lastly, Jeff notes an impactful lecture by Harriet Rumgay titled the Epidemic Burden of NAFLD and Cancer. This talk reminds that much of the daily work in liver health serves cancer prevention and primes Episode 13.2 for a deeper look into this topic.
If you enjoy the episode, have questions or interest around its contents and Fatty Liver disease, we kindly ask that you submit reviews wherever you download our discussions. Alternatively, you can write to us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
Surfing NASH returns to preview the second Innovations in NAFLD Care Workshop (INCBCN) to be held in Barcelona from 26-27 May, 2023. Conference founders and directors Jeff Lazarus and Jörn Schattenberg discuss what makes the event unique with Louise Campbell and Roger Green.
From the outset, Jeff underscores that this meeting fills an important gap between the heavy-hitting conferences in NAFLD and NASH. The INCBCN Workshop exists to explore dynamic and nuanced insights into both liver disease and holistic liver health in a smaller, more multidisciplinary forum. He recaps receiving positive feedback and building a follow-up program from last year’s inaugural event which witnessed state-of-the-art talks by leading KOLs across differing specialties. Jörn notes his enthusiasm around the practical component of this workshop in that it invests in ideas of implementation and engaging stakeholders beyond hepatology.
From here, Roger leads discussion into a breakdown of the sessions comprising the two days. Jeff immediately expresses excitement for an opening talk by Ramon Bataller which considers alcohol intake. He next points to Session 2 where Ken Cusi has organized discussion on the challenges of Fatty Liver from a diabetes perspective. Lastly, Jeff notes an impactful lecture by Harriet Rumgay titled the Epidemic Burden of NAFLD and Cancer. This talk reminds that much of the daily work in liver health serves cancer prevention. Roger recalls Hannah Mamuszka’s note from last week on the degree to which all obesogenic cancers are related to Fatty Liver disease.
At this point, Louise expands on the importance of early screening in populations who are unaware of their liver health and the need to drive education for those at risk to know when and what to ask their providers. She notes the nonlinear progression to liver cancer, a recently recurring theme on the podcast. She goes on to commend the convergence of fields, citing the various associations’ (including the American Heart Association and American Diabetes Association) growing inclusion of Fatty Liver in recommendations around risk assessment. Concluding Day 1, Jeff elaborates on a Patient Organisation session that includes a speaker from the World Organization of Family Doctors.
Moving into Day 2, friends of the podcast Alina Allen and Mazen Noureddin will be opening with two exciting topics. Alina will be giving a presentation titled Automation, Artificial Intelligence and Machine Learning for Patient Identification and Risk Stratification. Following, Mazen will be detailing How to Overcome Barriers of Implementation - Bridging the Gap Between Science and Current Care Pathways. Later there will be an entertaining debate on whether being vegetarian offers a cure for NAFLD (led by Shira Zelber-Sagi and Camilla Dalby Hansen). The group then discusses the input of allied health professionals in the program and a few additional elements yet to be mentioned, including Zobair Younossi on payers and a talk by Stephen Harrison. As the session winds down, Roger asks the panelists what the impact of this event will be and how will it inform next year's program. Stay tuned for more exclusive coverage from Barcelona and view the full program here.
If you enjoy the episode, have questions or interest around its contents and Fatty Liver disease, we kindly ask that you submit reviews wherever you download our discussions. Alternatively, you can write to us directly at questions@SurfingNASH.com.
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This conversation From the Vault starts with Chris Estes describing the processes he and his colleagues at the Center for Disease Analysis Foundation have used to build a disease model for NAFLD and NASH prevalence in 15 countries. Chris discusses some of the unique challenges that modeling NASH presents. Among other items, these include (a) spontaneous regression of disease; (b) “excess” mortality (mortality not from a liver disease where NASH is a contributing factor); and (c) interplay of demographics (gender, age, race, etc.) and co-morbidities (most notably Type 2 diabetes) with the disease.
When Chris ends his initial comments, Jörn Schattenberg asks about the viability of using obesity as the anchor for increasing prevalence estimates instead of diabetes, noting the varying definitions of BMI across countries. Chris notes that obesity is imperfect but adds that we have robust, stable, long-term obesity databases in most countries, whereas diabetes estimates are newer and many people with diabetes do not recognize they have the disease.
The last element in this conversation starts with Alina Allen noting that for clinical trial development, researchers test patients with a range of diagnostics. As a result, they do not need to develop estimates based on (or even linked directly to) obesity or diabetes. Alina asks what models can tell us that can help bring down high placebo rates in double-blinded, placebo-controlled clinical trials. Chris mentions meta-analyses as recently as seven years ago that exhibited negative disease progression over time and adds that any assessment of F3 (or even F2) fibrosis is affected by the concomitant disease.
This conversation is sponsored by Resoundant Resoundant, a Mayo Clinic company, and the developers of Magnetic Resonance Elastography. MRE is widely available with over 2000 locations worldwide and can be done as a low-cost, rapid exam in just 5 minutes. Together with PDFF, this quantitative exam is called an Hepatogram – a powerful non-invasive alternative to liver biopsy in many cases. For more information, visit www.resoundant.com on the web.Stay Safe and Surf On!
Last week, Jeff McIntyre of the Global Liver Institute introduced a draft report from the Institute for Clinical and Economic Review (ICER) on resmetirom and obeticholic acid for NASH. Jeff, an expert reviewer of the report, returns with the Surfers to expand on the contents, its shortcomings and potential implications. Among the panelists are Veronica Miller of the Liver Forum and new guest, Hannah Mamuszka, who is founder and CEO of Alva10.
This wrap-up conversation explores what the panels believe will be the impact of the ICER document for different stakeholder communities. Louise Campbell focuses on how stakeholders will look at price. Jörn Schattenberg uses Veronica phrase, "the genie is out of the bottle," to describe its impact. Veronica suggests that the paper will make an impression on how people think about the drugs, which is challenging given the analytical issues raised throughout the preceding conversations. Jeff asserts that patient involvement can help resolve some of these challenges and issues raised. He suggests the fact that ICER has introduced patients into the process as an excellent step forward. Hannah provides a variety of reasons why patients will be particularly important in this story. She notes that the generations of patients who are most affected by this disease, including Gen X and millennials, are people who tend not to visit primary care doctors. To hear the rest of her take and the final thoughts of Roger Green, tune in for this final session.
This episode was recorded in the presence of a live virtual audience. If you have interest in attending future recordings, please write to us at questions@SurfingNASH.com. If you enjoy the episode, have questions or interest around its contents and Fatty Liver disease, we kindly ask that you submit reviews wherever you download our discussions.
Stay Safe and Surf On!
Last week, Jeff McIntyre of the Global Liver Institute introduced a draft report from the Institute for Clinical and Economic Review (ICER) on resmetirom and obeticholic acid for NASH. Jeff, an expert reviewer of the report, returns with the Surfers to expand on the contents, its shortcomings and potential implications. Among the panelists are Veronica Miller of the Liver Forum and new guest, Hannah Mamuszka, who is founder and CEO of Alva10.
Veronica begins this segment with comments alluding to the dichotomy of the biopsy. On one hand, there is an emergence of AI-assisted histological assessment of fibrosis that lends fascinating insights into the nuances of the liver as an organ. On the other hand, the field is still stuck with a very blunt tool inadequate in assessing the effectiveness of a drug. She states that it “hurts to see that this is what happens when we are not applying the right diagnostic markers and tools.” She goes on to say that “in a couple of years we'll be in a totally different data zone” in terms of having much more quantitative data to employ when assessing the safety and efficacy of these drugs. This leads Roger Green to read out his least favorite sentence from the document: “the exact prevalence of NASH is uncertain since diagnosis requires liver biopsy and many patients with NAFLD do not undergo biopsy.”
The group goes on to discuss some more of the challenges in the document and data sets and before shifting to a payoff question around the impact of the ICER report. The panel notes that ICER has produced what is fundamentally private draft report with no impact on how the drug is assessed by the FDA. However, Hannah points out that while ICER sometimes issues updates, it's uncommon. She suggests that this trial provides no guidance on how we determine which patients are F2 or F3, which will provide a real challenge for payers trying to determine the economic impacts of the drugs. While ICER is a private organization, its recommendations carry weight with those assessing the value and pricing of new medications. As such, this report has the potential to leave a significant footprint in commercial space.
This episode was recorded in the presence of a live virtual audience. If you have interest in attending future recordings, please write to us at questions@SurfingNASH.com. If you enjoy the episode, have questions or interest around its contents and Fatty Liver disease, we kindly ask that you submit reviews wherever you download our discussions.
Stay Safe and Surf On!
Last week, Jeff McIntyre of the Global Liver Institute introduced a draft report from the Institute for Clinical and Economic Review (ICER) on resmetirom and obeticholic acid for NASH. Jeff, an expert reviewer of the report, returns with the Surfers to expand on the contents, its shortcomings and potential implications. Among the panelists are Veronica Miller of the Liver Forum and new guest, Hannah Mamuszka, who is founder and CEO of Alva10.
The session begins with questions from Roger Green around the report’s dated figures on disease prevalence. This leads Louise Campbell to note the intensity and speed in which the Fatty Liver field has developed over the previous decade. Provided this explosion in knowledge, she wonders whether we are able to effectively collect and implement the changes reflected by all this emerging data. Jeff and Roger add that socioeconomic shifts and the COVID-19 pandemic further amplify already swelling rates of incidence.
As this session winds down, Jörn Schattenberg poses a cogent line of questioning to consider in establishing a cost-effective intervention:
- Who was enrolled in the clinical trials?
- Where's the evidence that there is a subgroup of patients benefiting from the therapy?
- How can we identify them moving forward and outside of clinical trials?
This episode was recorded in the presence of a live virtual audience. If you have interest in attending future recordings, please write to us at questions@SurfingNASH.com. If you enjoy the episode, have questions or interest around its contents and Fatty Liver disease, we kindly ask that you submit reviews wherever you download our discussions.
Stay Safe and Surf On!
Last week, Jeff McIntyre of the Global Liver Institute introduced a draft report from the Institute for Clinical and Economic Review (ICER) on resmetirom and obeticholic acid for NASH. Jeff, an expert reviewer of the report, returns with the Surfers to expand on the contents, its shortcomings and potential implications. Among the panelists are Veronica Miller of the Liver Forum and new guest, Hannah Mamuszka, who is founder and CEO of Alva10.
Hannah begins this conversation by asserting that the report “understates the problem of the size of population we’re talking about.” She notes that it fails to consider the strength of data linking NAFLD and NASH to cardiovascular disease, liver cancers and even extrahepatic cancers. Hannah goes on to outline the relevant questions of commercial payers in the assessment of prospective pharmacotherapies:
- What is the size of the patient population and what is going to be the effect of coverage in terms of how many patients are we going to prevent from progressing to liver transplant?
- How many patients are we going to keep out of the hospital with chronic events?
Ultimately for Hannah, the analysis by ICER misses much of the potential cost savings of an effective drug. Louise echoes concerns surrounding the “difficulty in the communication and the language used throughout the report.”
This episode was recorded in the presence of a live virtual audience. If you have interest in attending future recordings, please write to us at questions@SurfingNASH.com. If you enjoy the episode, have questions or interest around its contents and Fatty Liver disease, we kindly ask that you submit reviews wherever you download our discussions.
Stay Safe and Surf On!
Last week, Jeff McIntyre of the Global Liver Institute introduced a draft report from the Institute for Clinical and Economic Review (ICER) on resmetirom and obeticholic acid for NASH. Jeff, an expert reviewer of the report, returns with the Surfers to expand on the contents, its shortcomings and potential implications. Among the panelists are Veronica Miller of the Liver Forum and new guest, Hannah Mamuszka, who is founder and CEO of Alva10.
In this opening conversation, Roger Green introduces the ICER document and prompts panelists to share initial impressions around the assumptions and platforms that underlie it. Before diving in, Jörn Schattenberg briefly recaps the benefit behind obtaining relatively large datasets on safety and efficacy for resmetirom and obeticholic acid. Veronica asserts that she is “quite astounded” that this report would be generated before the emergence of a formal, peer-reviewed publication on the data. This leads Roger to note the competing interests of acquiring unassailable data (which can take endless time) versus serving the more immediate needs of patients desperate for solutions now.
Jeff discloses that while he is pleased with ICER’s inclusion of patient participation in the report, several critical shortcomings need addressing. The major concern: a statement claiming that NASH and NAFLD are not progressive diseases. Jörn responds to this statement with an anecdote from his specialty care clinic where patients do in fact arrive symptomatic as related to their troubled liver health. Surf on to the next conversation to hear what the others think.
This episode was recorded in the presence of a live virtual audience. If you have interest in attending future recordings, please write to us at questions@SurfingNASH.com. If you enjoy the episode, have questions or interest around its contents and Fatty Liver disease, we kindly ask that you submit reviews wherever you download our discussions.
Stay Safe and Surf On!
Last week, Jeff McIntyre of the Global Liver Institute introduced a draft report from the Institute for Clinical and Economic Review (ICER) on resmetirom and obeticholic acid for NASH. Jeff, an expert reviewer of the report, returns with the Surfers to expand on the contents, its shortcomings and potential implications. Among the panelists are Veronica Miller of the Liver Forum and new guest, Hannah Mamuszka, who is founder and CEO of Alva10.
10:05 Introducing the ReportJörn Schattenberg briefly revisits the relatively large datasets on these two drugs. Veronica is “quite astounded” that this report would be generated before the emergence of a formal peer-reviewed publication. While Jeff is pleased with ICER’s inclusion of patient participation in this report, he underscores critical concern around a statement claiming that NASH and NAFLD are not progressive diseases.
21:31 Assessment of Disease PrevalenceHannah asserts that the report “understates the problem of the size of population" and fails to consider the strength of data linking NAFLD and NASH to cardiovascular outcomes, liver cancers and beyond. She suggests that commercial payers are looking to address the following questions in their assessment of the drug candidates:
- What is the size of the patient population and what is going to be the effect of coverage in terms of how many patients are we going to prevent from progressing to liver transplant?
- How many patients are we going to keep out of the hospital with chronic events?
Ultimately for Hannah, the report's analysis misses many of the potential cost savings of an effective drug.
29:06 Keeping Pace with Field AdvancementsLouise notes the intensity and speed in which the Fatty Liver field has developed over the previous decade. Provided this explosion in knowledge, she wonders whether we are able to effectively collect and implement the changes reflected by all this emerging data. Jeff and Roger add that socioeconomic shifts and the COVID-19 pandemic amplify already swelling rates of incidence. Jörn poses a cogent line of questioning to consider in establishing cost-effective interventions:
- Who was enrolled in the clinical trials?
- Where's the evidence for a subgroup of patients benefiting from therapy?
- How can we identify them moving forward and outside of clinical trials?
38:55 Biopsy and BiomarkersVeronica describes the dichotomy of biopsy. On one hand, AI-assisted histological assessment of fibrosis lends fascinating insights into the nuances of the liver as an organ. On the other, biopsy is still a very blunt tool inadequate in assessing the effectiveness of a drug. She states that it “hurts to see that this is what happens when we are not applying the right diagnostic markers and tools” and that “in a couple of years we'll be in a totally different data zone” in terms of having much more quantitative data to employ when assessing the safety and efficacy of these drugs.
48:36 Implications and Final ThoughtsAs the session winds down, the group considers various other aspects for which this document can potentially have an impact. Comments range from notes on pricing to what FDA factors for approval.
This episode was recorded in the presence of a live virtual audience. If you have interest in attending future recordings, please write to us at questions@SurfingNASH.com. If you enjoy the episode, have questions or interest around its contents and Fatty Liver disease, we kindly ask that you submit reviews wherever you download our discussions.
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Last year on Thursday, June 9th we covered #NASHDay 2022, the 5th annual celebration of International NASH Day by the world’s largest liver patient advocacy organization, the Global Liver Institute. To celebrate the occasion, Stephen Harrison joined Jörn Schattenberg, Louise Campbell and Roger Green to comment on one crucial trend or event that most signified what the last year has meant in the Fatty Liver community.
This conversation includes three sections:
- First, Roger discusses the Law of Unintended Consequences in the context of the FDA Complete Response Letter to Intercept Pharmaceuticals over obeticholic acid. This was an event that many feared would bring all momentum around Fatty Liver disease to a standstill but, two years later, has driven real bursts of creative energy and innovative problem solving centered around the disease rather than a drug.
- Second, Stephen and Jörn offer impassioned statements that the providers will never give up on addressing the challenges of NASH, both because, as Stephen describes, it is not in their character and because, as Jörn describes, “this disease is not going away.” As long as people are dying too young from the effects of NASH and HCC, he contends, the fight will continue.
- Finally, Roger asked the panelists for bold predictions about what will have changed before we come together a year from now to celebrate the 6th International NASH Day.
This final segment with Jeff McIntyre of the Global Liver Institute (GLI) explores the panelists’ final thoughts around optimisms and worries for the Fatty Liver field going forward. Next week, the Surfersinvite you to join a live session covering the ICER draft pricing recommendations on resmetirom and obeticholic acid (OCA).
This exclusive opportunity for the Surfing NASH community to attend the live recording as audience members will take place on Monday, March 13th at 1700h CET, 1600h. In doing so, you will be able to voice questions and feedback on the pressing topic of imminent NASH drug approvals. To reserve a spot, please visit the following link: https://bit.ly/Surf-Live-With-Us.
To learn more about this opportunity, follow us on LinkedIn and subscribe to the newsletter. Alternatively, you can write to us directly at questions@SurfingNASH.com.
We look forward to surfing together soon!
The Surfers are joined by Jeff McIntyre of the Global Liver Institute (GLI) for a thought-provoking impromptu session on what’s happening thus far for the Fatty Liver field in 2023. Roger Green begins this conversation by introducing a timely Lancet paper which coincided with the previous episode's focus on pediatric and adolescent NAFLD and NASH. The US-based study suggests that in five randomly allocated centers from 2002 to 2018, annual increase in incidence of Type-2 diabetes among 10-19 year-olds was a staggering 5% per year. He connects these findings to aforementioned ideas around public health policy and nutrition. Louise Campbell comments on how this influences the public perspective of Type-2 diabetes and the role of family history. Jörn Schattenberg adds that “genes are one thing” but the passing of behavior from generation to generation as a function of educational influence is a serious socioeconomic issue to consider. In closing, Jeff suggests that a critical predictor of whether a child is going to be obese is whether the parents are overweight or obese.
If you enjoy the episode, have questions or interest around its contents and Fatty Liver disease, we kindly ask that you submit reviews wherever you download our discussions. Alternatively, you can write to us directly at questions@SurfingNASH.com.
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The Surfers are joined by Jeff McIntyre of the Global Liver Institute (GLI) for a thought-provoking impromptu session on what’s happening thus far for the Fatty Liver field in 2023. In this conversation, Jeff continues on collaborative work by GLI to more formally “medicalize” obesity as a term considerate of genetic backgrounds and metabolic dynaminisms. He relates this grappling around nomenclature to that experienced in the Fatty Liver forum. Comments shift toward the subject of nutrition and an ominous landscape of public health policy. Jeff calls for hepatology associations to join efforts in assessing package nutrition labeling, advocating for reductions of high fructose corn syrup and other measures of rectifying harmful food marketing to children. He notes there to be a conversation around rule-making happening at the FDA right now on what defines a “healthy” food. Jeff asserts that, “frankly, chronic disease is really underrepresented in that conversation.” Worse yet, representatives of those companies pushing the agenda of junk food are ascertained to be present and lobbying for their products one way or another. At this point, the other panelists voice impressions to these concerns.
If you enjoy the episode, have questions or interest around its contents and Fatty Liver disease, we kindly ask that you submit reviews wherever you download our discussions. Alternatively, you can write to us directly at questions@SurfingNASH.com.
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The Surfers host a thought-provoking impromptu session on what’s happening thus far for the Fatty Liver field in 2023. Jörn Schattenberg leads this conversation with comments around diagnostic and therapeutic advancements following the momentum gathered at NASH-TAG in January. He points to the large number of abstracts (estimated at over 2500!) submitted to the upcoming EASL Congress held in Vienna this June. While drugs are leading the way, Jörn insists diagnostics are closely following and contributing to "excitement on both borders.” Roger Green notes activity around organizing trials that incorporate non-invasive endpoints.
Louise Campbell adds her highlight to be the recent AASLD guidance and its focus on clarifying CAP scores for improved FibroScan assessment. This is joint with eager anticipation of a NICE approval for access to FibroScan in the primary care setting. Roger comments on emerging competitor technologies, such as E-Scopics, and their influence on industry uptake of NITs. Combined with the various emerging guidelines and guidances, more doctors and specialties should begin focusing on how and when to test. Louise notes the potential challenges behind adopting liver-conscious practices for endocrinology and cardiology clinics in that there will be questions around how exactly this initiative is administered. However, these are exciting and surmountable challenges with rewarding implications. In Louise’s experience, “if you find real time with that person in the room, you can really make a change.” Roger connects these ideas around frontline screening to the podcast’s latest ventures in launching the Rising Tideseries available at SurfingNASH.com. Lastly, he describes emerging energies around payer dynamics and drug utilization in the US.
If you enjoy the episode, have questions or interest around its contents and Fatty Liver disease, we kindly ask that you submit reviews wherever you download our discussions. Alternatively, you can write to us directly at questions@SurfingNASH.com.
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The Surfers are joined by Jeff McIntyre of the Global Liver Institute for a thought-provoking impromptu session on what’s happening thus far for the Fatty Liver field in 2023. The panelists touch on topics which elicit responses ranging from positive excitement around scientific developments to head-scratching concern over public policy positions.
06:31Jörn Schattenberg opens with comments on diagnostic and therapeutic advancements which follow the momentum gathered at an energizing NASH-TAG conference in January. He specifically points to the numerous abstracts (estimated at over 2500!) submitted that will contribute to a scientifically-stimulating EASL Congress held in Vienna this June. Jörn emphasizes that while drugs are leading the way, diagnostics are closely following and contributing to "excitement on both borders.” Louise Campbell adds her thoughts around the recent AASLD guidance and its focus on clarifying CAP scores for improved FibroScan assessment. Roger Green notes emerging competitor technologies, such as E-Scopics, and their influence on industry uptake of NITs.
19:17Jeff expands on the trajectory of imminent drug approvals of obeticholic acid and resmetirom. He goes on to express mixed levels of enthusiasm around a draft report from ICER which includes pricing estimates for these drugs. The contention lies in the draft’s reference to NASH as a non-progressive disease - a position that the panelists clearly debunk. He next speculates on the future standard for noninvasive testing and biomarkers. His comments emphasize the “need for a noninvasive that can be scaled with the least amount of burden to primary care providers and the patient populations that need them.” Roger Green points to the various guidelines’ referral to FIB-4 as such a test.
29:31Jeff introduces collaborative work by GLI which sets out to more formally “medicalize” obesity as a term considerate of genetic backgrounds and metabolic dynaminisms. He relates this discussion around nomenclature to that experienced in the Fatty Liver space. Conversation segues to the subject of nutrition and the often ominous landscape of public health policy.
37:14Roger introduces a timely Lancet paper which coincided with Surfing NASH’s focus on pediatric and adolescent NAFLD and NASH. The US-based study suggests that in five randomly allocated centers from 2002 to 2018, annual increase in incidence of Type-2 diabetes among 10-19 year-olds was a staggering 5% per year. He connects the findings to the aforementioned ideas around public health policy and nutrition. As the session winds down, Roger invites the panelists to provide the most significant and optimistic thing they will be touching over the next three months followed by the greatest fear each has in the same space. Listen to the full feature to hear their responses and the rest of this well-balanced conversation.
If you enjoy the episode, have questions or interest around its contents and Fatty Liver disease, we kindly ask that you submit reviews wherever you download our discussions. Alternatively, you can write to us directly at questions@SurfingNASH.com.
This episode From the Vault comes from the 2022 Liver Conference, where over 400 liver disease stakeholders gathered in Scottsdale, Arizona for the event sponsored by the Chronic Liver Disease Foundation (CLDF). The main meeting ran on a Friday and Saturday and was preceded on Thursday by a half-day session devoted exclusively to NASH (NASH Connect). Episode 15.3 of Season 3 and its conversations capture some of the thinking that went into the program design and some highlights of the NASH-related sessions.
This conversation focuses on the issue of pediatric NASH and NAFLD. Naim Alkhouri discusses the urgent need to include pediatric and adolescent patients in clinical trials, while Louise Campbell asked whether we could possibly get results soon enough to help today’s youngsters with NAFLD or NASH. Marcelo Kugelmas stated his firm conviction that we need to prove safety and efficacy available, but that there are many other steps we can take (lifestyle modification, for one) if we have adequate commitment. This led Roger Green to note government action in the UK to improve the informational quality of food and fast-food restaurant advertising and to ask whether something similar could happen in the U.S. This sparked discussion about food labelling in the UK, Michele Obama’s program in the US, the impact of sugar taxes and food advertising bans during certain times of day, and the overall potential for government activities to succeed. In the end, the group agreed that with money, an advertising campaign to back these kinds of issues might have an excellent result.
This episode and conversations are sponsored by Madrigal Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company pursuing novel therapeutics for NASH. Madrigal’s lead candidate, resmetirom, is a once daily, oral, thyroid hormone receptor (THR)-β selective agonist that is designed to target key underlying causes of NASH in the liver. Resmetirom is currently being evaluated in two Phase 3 clinical studies, MAESTRO-NASH and MAESTRO- NAFLD-1, designed to demonstrate multiple benefits in patients with NASH. For more information, visit www.madrigalpharma.com.
In yet another topical debut, Surfing NASH explores pediatric and adolescent Fatty Liver disease, its alarming incidence rate and developing the field's understanding around how to treat a vulnerable subpopulation. The Surfers are joined in discussion by Naim Alkhouri and chief of Gastroenterology, Hepatology and Nutrition at Children’s Hospital Los Angeles, Rohit Kohli, for a special session which illuminates a public health crisis intimate to the two extremely knowledgeable guests.
Roger Green leads this final conversation with an apt metaphor. He suggests that a population facing increasing severity downstream is like dealing with a momentous snowball rolling downhill and amassing trouble. With this in mind, he asks the panelists where they think we have the ability in advance of drug trials for pediatrics to intervene and either slow or ideally eviscerate the snowball. Rohit responds that it depends on the slope of the hill, and every child, because of underlying genetics and environmental influences, has a different slope. Both Jörn Schattenberg and Naim describe this as an arena of prevention. Finally, Louise Campbell raises grave concern over coping with the enormous industry influence on the milieu of nutrition surrounding children.
If you have questions or interest around pediatric and adolescent Fatty Liver disease, we kindly ask that you submit reviews wherever you download our discussions. Alternatively, you can write us directly at questions@SurfingNASH.com.
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In yet another topical debut, Surfing NASH explores pediatric and adolescent Fatty Liver disease, its alarming incidence rate and developing the field's understanding around how to treat a vulnerable subpopulation. The Surfers are joined in discussion by Naim Alkhouri and chief of Gastroenterology, Hepatology and Nutrition at Children’s Hospital Los Angeles, Rohit Kohli, for a special session which illuminates a public health crisis intimate to the two extremely knowledgeable guests.
This conversation begins with Louise Campbell’s note that, on average, it takes 17 years for clinical trials to be implemented in real world settings. She asks whether it’s an option to collect noninvasive clinical data and determine whether this alone instigates behavioral change despite it not proving clinical diagnosis. This sparks the panelists to explore ideas around how to effectively introduce lifestyle interventions for children and families at a societal scale. It's noted with unanimous agreement that nutritional matters are family matters. Roger Green adds comments on the influence of school education in trickling information on liver health to homes. Louise asserts that from a cost analysis perspective, screening children with assessments which include liver health can actually suppress or prevent cardiovascular events in the future. This prompts Rohit to describe guidelines that utilize annual physicals with adolescents as an opportunity to track liver health.
At the end of the session, Naim highlights several more recent studies that are developing the field’s understanding of early life risk factors and the natural history of this disease. His final comments consider the implications of prescribing therapies to adolescents progressing in instances where lifestyle interventions fail to halt disease progression.
If you have questions or interest around pediatric and adolescent Fatty Liver disease, we kindly ask that you submit reviews wherever you download our discussions. Alternatively, you can write us directly at questions@SurfingNASH.com.
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In yet another topical debut, Surfing NASH explores pediatric and adolescent Fatty Liver disease, its alarming prevalence and developing the field's understanding around how to treat this vulnerable subpopulation. The Surfers are joined in discussion by Naim Alkhouri and chief of Gastroenterology, Hepatology and Nutrition at Children’s Hospital Los Angeles, Rohit Kohli for a special session which illuminates a critical issue intimate to the two extremely knowledgeable guests.
Jörn Schattenberg steers this conversation toward the cardiometabolic complications behind patients living longer with Fatty Livers. Naim describes a paper which sought to strengthen understanding of epidemiology by histopathology reports in Sweden. With access to virtually all liver biopsies in the country, the group set out to identify cardiovascular disease emerging in patients previously diagnosed with NASH under the age of 25. The conclusion: compared with matched population controls, patients with biopsy-proven NAFLD had significantly higher incidence of major adverse cardiovascular events. Excess risk was evident across all stages of NAFLD and increased with worsening disease severity.
At this point, Rohit comments on the role and appropriateness of bariatric surgery in adolescents to mitigate the long-term metabolic consequences of obesity. Louise Campbell asks for clarification around histopathological differences between adolescents and adults. Rohit and Naim then describe zonal analysis which characterizes an alternate pattern of progressive NAFLD in children whereby the inflammatory foci is more portal-centric. It’s noted that a shift typically occurs around the age of 12 and 13 when hepatocyte ballooning becomes a predominant feature rather than portal inflammation. Naim asserts this has great implications for designing histology-based pediatric trials because the resolution of hepatocellular ballooning is considered a hallmark of NASH resolution.
The remainder of the session considers unique challenges associated with establishing NITs as endpoints for trials with adolescents. In this context, Rohit and Naim describe a spate of noninvasive technologies and tools with varying inaccuracies. FIB-4 is noted to be particularly inadequate in assessing the pediatric population. Finally, Naim comments on the need for regulatory guidance as significant fibrosis at an early age may require use of medications. He suggests that it’s critical to avoid conducting the same repeat biopsies as designed in Phase 3 clinical clinical trials for adults.
If you have questions or interest around pediatric and adolescent Fatty Liver disease, we kindly ask that you submit reviews wherever you download our discussions. Alternatively, you can write us directly at questions@SurfingNASH.com.
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In yet another topical debut, Surfing NASH explores pediatric and adolescent Fatty Liver disease, its alarming prevalence and developing the field's understanding around how to treat this vulnerable subpopulation. The Surfers are joined in discussion by Naim Alkhouri and chief of Gastroenterology, Hepatology and Nutrition at Children’s Hospital Los Angeles, Rohit Kohli for a special session which illuminates a critical issue intimate to the two extremely knowledgeable guests.
Roger Green prefaces this conversation with the observation that as a pandemic of Fatty Liver disease grows at boggling speed, so too does NAFLD and NASH in younger populations. While this recognition may in part be attributed to improved methodologies, it is evident that lifestyle norms around diet and exercise continue to exacerbate the problem. Rohit expands on the notion that an environmental shift has contributed to the dilemma, referring to the emergence of accessible, low cost, calorically-loaded processed foods that are not only to be available at home but also within schools. He refers to a study of a controlled cohort on incidence of NAFLD in children from 2009-2018. Strikingly, it was determined that the incidence of NAFLD diagnosis significantly increased over time from 36.0 per 100,000 in 2009 to 58.2 per 100,000 in 2018 (P < .0001). Still, many children may remain undiagnosed. Roger comments on the potential of geopolitical events during this study that could influence shift of a nutritional landscape.
Naim adds that estimates around prevalence also increase when considering adolescents as opposed to children. He highlights that 17-25% of adolescents are suffering from “not just NAFLD, but actually NASH and significant fibrosis.” A combination of genetic backgrounds and complicating conditions ranging from obesity to sleep apnea are entangled with disease progression. Lastly, Naim shares a sobering anecdote from his clinic of a 13 year-old patient with biopsy-proven cirrhosis.
If you have questions or interest around pediatric and adolescent Fatty Liver disease, we kindly ask that you submit reviews wherever you download our discussions. Alternatively, you can write us directly at questions@SurfingNASH.com.
Stay Safe and Surf On!
In yet another topical debut, Surfing NASHexplores pediatric and adolescent Fatty Liver disease, its alarming prevalence and developing the field's understanding around how to treat this vulnerable subpopulation. The Surfers are joined in discussion by Naim Alkhouri and chief of Gastroenterology, Hepatology and Nutrition at Children’s Hospital Los Angeles, Rohit Kohli. This is a special session which illuminates a critical issue intimate to two extremely knowledgeable guests. Rich with invaluable insights, the panelists elaborate on the following major themes:
08:55Roger Green prefaces this conversation with the observation that as a pandemic of Fatty Liver disease grows at boggling speed, so too does NAFLD and NASH in younger populations. While this may in part be attributed to improved methodologies, it is evident that lifestyle norms around diet and exercise continue to exacerbate the problem. Rohit expands on this notion by sharing apt research examples which demonstrate swelling prevalence in younger populations. He suggests that while methodologies have improved, indeed also we are witnessing increasing incidence. Most strikingly, Naim refers to an anecdote witnessed in his clinic of a 13 year-old patient with biopsy-proven cirrhosis.
16:05Jörn Schattenberg steers discussion toward the cardiometabolic implications behind patients living longer with Fatty Livers. Naim describes a paper he co-authored which sought to strengthen epidemiology by histopathology reports in Sweden. With access to all liver biopsies in the country, the group set out to identify cardiovascular disease emerging in patients previously diagnosed with NASH under the age of 25. He details results which underscore a swathe of associations linking Fatty Liver to metabolic complications. Rohit adds comments around the role and appropriateness of bariatric surgery in adolescents to mitigate the long-term metabolic consequences of obesity. Louise Campbell prompts explanation around histopathological differences in adolescents versus adults, and what's unique in the use of NITs for younger patients.
28:37The group continues to consider how to accelerate clinical trial learnings into real world implementations. This develops into ideas around effectively introducing lifestyle intervention to children at a societal scale. It's noted and agreed that nutritional matters are family matters. Rohit describes guidelines which utilize annual physicals with adolescents as an opportunity to track liver health. Naim goes on to describe factors contributing to our understanding of early life risk factors and natural history of disease.
38:22As the session winds down, Roger asks the panelists for what impact they envision emerging trials and drugs to have in the pediatric space. Each provides thought-provoking responses and Louise raises grave concern over coping with the enormous industry influence on the milieu of nutrition for children. Listen to the full feature to hear the various reactions.
If you enjoy this episode, have questions or interest around pediatric and adolescent Fatty Liver disease, we kindly ask that you submit reviews wherever you download our discussions. Alternatively, you can write us directly at questions@SurfingNASH.com.
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This week, SurfingNASH is offering conversation segments to showcase our new series, The NASH Tsunami in Diabetes: Getting Ahead of the Rising Tide. Rising Tide, as we call it, is a subscription-only series targeted at the primary care physicians, endocrinologists and allied health professionals who provide front-line treatments for patients living with Type 2 Diabetes and/or obesity. In this episode From the Vault, Jeff Lazarus and Roger Green discuss the ease of creating valuable metrics in a comprehensive care model, while our three practitioners -- Stephen Harrison, Jörn Schattenberg and Louise Campbell -- dive further into how they believe this model will improve care.
KEY POINT: Broadening the number and diversity of health care providers assigned to each individual patient will improve care by improving focus on the areas that count. It is important that system designers ask the right questions and answer them rigorously in context; it is undesirable for the systems to look more or less identical.
If you enjoy episode 9 and its introduction to Rising Tide, please visit our website and sign up to listen to the full discussions and more exclusive content. We also kindly ask that you submit reviews wherever you download our discussions or, alternatively, write to us directly at questions@SurfingNASH.com.
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This week, SurfingNASH is offering conversation segments to showcase our new series, The NASH Tsunami in Diabetes: Getting Ahead of the Rising Tide. Rising Tide, as we call it, is a subscription-only series targeted at the primary care physicians, endocrinologists and allied health professionals who provide front-line treatments for patients living with Type 2 Diabetes and/or obesity. This sample session comes from the just-released Season 2 debut which focuses comprehensively on a new chapter of the podcast and why 2023 might be “the best year ever” for Fatty Liver.
The group considers what made 2022 special. Mazen highlights Madrigal’s positive topline results from the Phase 3 trial of resmetirom for treatment of NASH and liver fibrosis. He also notes Intercept’s study on evaluating the safety and efficacy of obeticholic acid in patients with compensated cirrhosis. Ken underscores the development of algorithms for identifying and diagnosing patients. He is optimistic about different societies aligning to define pathways because NAFLD and NASH are metabolic diseases at the center of converging fields. Roger states his highlight of 2022 to be movement toward noninvasive tests and away from biopsies.
Conversation expands on the NASH drug pipeline. Mazen cites utility in GLP-1 medications, like semaglutide, and the pan-PPAR agonist, lanifibranor. Roger adds that efruxifermin, an FGF21, has the potential to regress fibrosis in pre-cirrhotic patients. Ken notes it was previously thought that a monotherapy would cure NASH. Today, the promise of combination therapies demonstrates benefits which positively impact weight and other cardiometabolic variables. Roger echoes the idea that the ability to stop progression and reduce steatosis is an achievable target today.
Shifting to diagnostics, Roger explains the fading narrative of biopsy as a gold standard. Mazen emphasizes need to screen Type 2 diabetics and those with two or more metabolic risk factors. He introduces a simple test, called FIB-4, which helps to estimate the amount of scarring in the liver. FIB-4 is a basic computation that factors a patient’s age, liver enzymes and platelet count. He also describes transient elastography FibroScan, a noninvasive method evaluating liver fibrosis by measurement of liver stiffness. Lastly, he details the enhanced liver fibrosis (ELF) test, a blood test that provides a score reflecting the severity of liver fibrosis. A key message: patients with Stage 2 fibrosis and higher need to be referred as this is the population with significant risk of facing severe complications. Ken builds on the idea behind criticality in screening and identifying early in disease progression. There are simply not enough hepatologists to treat the millions of patients with liver disease.
After more notes around guidelines and practical, systemic approaches to navigate widespread prevalence, the panelists offer closing comments. The final points focus on: 1) biggest takeaways for frontline treaters, and 2) most exciting elements to emerge in this space in 2023.
If you enjoy this preview, please visit our website and sign up to listen to the full episode and more exclusive content. We also kindly ask that you submit reviews wherever you download our discussions or, alternatively, write to us directly at questions@SurfingNASH.com.
The Rising Tide podcast series and all episodes are produced under a non-restricted grant from Novo Nordisk. Novo Nordisk has neither influenced nor reviewed the contents of this podcast in any way. This content represents the views of the speakers and does not necessarily represent the views of Novo Nordisk. The content herein is for educational purposes only and should not be taken as medical advice.
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This week, SurfingNASH is offering conversation segments to showcase our new series, The NASH Tsunami in Diabetes: Getting Ahead of the Rising Tide. Rising Tide, as we call it, is a subscription-only series targeted at the primary care physicians, endocrinologists and allied health professionals who provide front-line treatments for patients living with Type 2 Diabetes and/or obesity. This preview looks at drug choices prescribers can make today for patients with Type 2 Diabetes Mellitus and obesity that have positive impact on Fatty Liver disease. In addition to co-hosts Dr. Ken Cusi and Roger Green, panelists for this discussion include endocrinologist Dr. Scott Isaacs, second author of the recent AACE guidelines, and hepatology researcher Dr. Naim Alkhouri.
Ken notes that we are living in a period where the paradigm around treating chronic metabolic conditions is shifting. In a world where one in five patients with T2DM lives with clinically significant fibrosis, Ken states providers can no longer ignore the liver when making treatment decisions about diabetes. He also suggests that hepatologists need to become more comfortable using medications that were previously reserved for diabetes.
At this point, Naim and Scott join the conversation. Naim begins by discussing EDICT, a trial that compared the standard T2DM regimen of the day (metformin, followed by the sulfonylurea glipizide and then insulin) to a first-line combination therapy of metformin, the GLP-1 agonist exenatide and the PPAR pioglitazone. At the end of this six-year period, the researchers found meaningful, statistically significant differences in three key Fatty Liver parameters: prevalence of NAFLD (69% vs. 31%); clinically significant fibrosis (26% vs. 7%); and percentage fat in the liver (12.5% vs. 8.5%). It also found that patients achieved a lower HbA1c level (6.0% with the combination, vs. 6.8% in the standard treatment group).
In response to a question from Roger, Ken identifies three majors lessons of the last 10 years:
7 of 10 Americans with T2D have a fatty liver; those with NAFLD but not T2D see their chances of becoming diabetic and , separately, developing cardiovascular disease double.
15-20% of Americans with T2D also exhibit moderate-to-advanced cirrhosis.
GLP-1s, as a class, address multiple factors of chronic metabolic disease. They reduced HbA1c, promote and maintain significant weight loss, and slow progression of fibrosis.
Naim expresses a concern that many doctors treating patients with T2D do not consider NASH. A Cleveland Clinic assessment of ICD-10 codes demonstrated that only 5% of T2D patients were coded for NAFLD. This means the 2/3 of the T2D patients in that system have fatty livers and were never evaluated! Similarly, ~2/3 of the patients who present with cirrhosis in his clinic were never told that they had NAFLD. In Naim’s view, NAFLD should be a disease for primary care and endocrinology to treat, while it should be hepatologists that treat NASH.
If you enjoy this preview, please visit our website and sign up to listen to the full episode and more exclusive content. We also kindly ask that you submit reviews wherever you download our discussions or write to us directly at questions@SurfingNASH.com.
The Rising Tide podcast series and all the episodes are produced under a non-restricted grant from Novo Nordisk. Novo Nordisk has neither influenced nor reviewed the contents of this podcast in any way. This content represents the views of the speakers and does not necessarily represent the views of Novo Nordisk. The content herein is for educational purposes only and should not be taken as medical advice.
Stay Safe and Surf On!
This week, SurfingNASH is offering conversation segments to showcase our new series, The NASH Tsunami in Diabetes: Getting Ahead of the Rising Tide. Rising Tide, as we call it, is a subscription-only series targeted at the primary care physicians, endocrinologists and allied health professionals who provide front-line treatments for patients living with Type 2 Diabetes and/or obesity. This preview comes from our second episode which focused on the new AACE Fatty Liver Guidelines.
The panelists include four authors of the guidelines: first author Dr. Ken Cusi from the University of Florida, third author Dr. Diana Barb, also from the University of Florida, and the two leading AASLD representatives in this project, Dr. Zobair Younossi of INOVA Health Systems and Dr. Maru Rinella of the University of Chicago. Dr. Younossi focuses his discussion on the epidemiology of the disease and what it suggests in terms of treatment goals and priorities. Dr. Cusi identifies the two main messages of the guidelines: the importance of FIB-4 as a screening tool and the fact that even today, with no recently approved NASH drugs on the market, there are therapeutic choices providers can make that will benefit NASH patients. Dr. Barb discusses in detail prescribing decisions that can benefit diabetes patients at risk of progressing to significant NASH fibrosis and beyond. Dr. Rinella lends comments throughout from her own perspective and that of AASLD. This fast-paced episode provides a tremendous amount of information while remaining accessible and easy to follow.
If you enjoy the preview, please visit our website and sign up or sign in to listen to the full episode and more exclusive content. We also kindly ask that you submit reviews wherever you download our discussions or, alternatively, write to us directly at questions@SurfingNASH.com.
The Rising Tide podcast series and all the episodes are produced under a non-restricted grant from Novo Nordisk. Novo Nordisk has neither influenced nor reviewed the contents of this podcast in any way. This content represents the views of the speakers and does not necessarily represent the views of Novo Nordisk. The content herein is for educational purposes only and should not be taken as medical advice.
Stay Safe and Surf On!
This week, SurfingNASH is offering conversation segments to showcase our new series, The NASH Tsunami in Diabetes: Getting Ahead of the Rising Tide. Rising Tide, as we call it, is a subscription-only series targeted at the primary care physicians, endocrinologists and allied health professionals who provide front-line treatments for patients living with Type 2 Diabetes and/or obesity.
This sample session comes from the debut episode which focuses on research that has led AACE to issue guidelines, AGA to propose clinical care pathways and AHA to produce a white paper on the links between Fatty Liver Disease and CVD Risk. Endocrinology researcher and key opinion leader Ken Cusi discusses his work looking at NAFLD and NASH in diabetic patient populations. He covers studies confirming that patients with diabetes are at least twice as likely to have NAFLD or NASH as non-diabetics. He notes that this effect is confirmed in overweight as well as obese patients and is proven independent of obesity (an important note: the two together are worse than either alone). In practical terms, he asserts that primary care and endocrinology clinics are the places we can identify NAFLD and early NASH before these become later-stage fibrosis or cirrhosis requiring attention from hepatologists. In that context, he notes that twice as many patients in an endocrinology clinic will test positive for NAFLD or NASH compared to a primary care clinic, thus making endocrinologists a vital target group for earlier identification and treatment of Fatty Liver Disease. In his practice, Ken advocates for every patient to receive a FIB-4 test, which can be found in most EMR systems and is an inexpensive, reasonably reliable negative predictor for F3 or F4 status.
Next, hepatology researcher and key opinion leader Kathleen Corey discusses some of her research on the link between CVD and NAFLD. Two key conclusions: over a relatively short period after initial induction into the study (median of 25.5 months), the presence of NAFLD causes a 70% increase in relative risk (4.1% vs. 2.6%) of a Major Adverse Cardiovascular Event (MACE). She agrees with Ken’s suggestion about FIB-4. She also notes the trend of primary care physicians to discontinue statins if the patient’s ALT level starts to rise and cautions that this step is likely to increase patient risk.
Finally, Kay Pepin, Director of Research Translation for Resoundant Inc. under joint appointment with the Mayo Clinic, discusses research demonstrating that a relatively simple MRE session can provide the information necessary to determine the likelihood that fibrosis will advance to cirrhosis or compensated cirrhosis will advance to decompensated states. She also notes that with insurance coverage, this is not an expensive test for many people. By adding a simple MRI module to the MRE session, physicians can derive a significant amount of additional information.
If you enjoy this preview, please visit our website and sign up to listen to the full episode and more exclusive content. We also kindly ask that you submit reviews wherever you download our discussions or, alternatively, write to us directly at questions@SurfingNASH.com.
The Rising Tide podcast series and all the episodes are produced under a non-restricted grant from Novo Nordisk. Novo Nordisk has neither influenced nor reviewed the contents of this podcast in any way. This content represents the views of the speakers and does not necessarily represent the views of Novo Nordisk. The content herein is for educational purposes only and should not be taken as medical advice.
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This week, SurfingNASH.com is offering a 17-minute section of our new series, “The NASH Tsunami in Diabetes; Getting Ahead of the Rising Tide.” Rising Tide, as we call it, is a subscription-only series targeted at the primary care physicians, endocrinologists and allied health professionals who provide front-line treatments for patients living with Type 2 Diabetes and/or obesity.
This conversation is an opportunity for NASH Tsunami listeners to learn about the series and why to subscribe by listening to this 17-minute segment of a previously unpublished episode from October, 2022, that is as timely today as when it was recorded.
The full episode follows the experience of Fatty Liver Alliance Founder and President Michael Betel when he submitted to extensive non-invasive diagnostic testing to determine his own Fatty Liver status. Mike’s experience, which he recorded for educational purposes and posted on Facebook, was a somewhat confusing experience due to inconsistencies in the results of various tests. In the episode, Rising Tide co-host Dr. Kenneth Cusi and episode guest (and NASH Tsunami co-host) Professor Jörn Schattenberg join Mike and co-host Roger Green to review Mike’s test results and recommend courses of action for Mike to take. In this process, the group also discusses the Fatty Liver guidelines from AASLD, AACE, AGA and others and the pivotal role that front-line screening plays in these guidelines.
This segment of the episode shares Mike’s story and some of the feedback he received from Ken, Jörn and Roger. At the end of the episode, Roger provides guidance on how listeners can subscribe to the Rising Tide series.
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In this conversation From the Vault, panelists preview the inaugural Innovations in NAFLD Care Workshopwhich took place in Barcelona on May 6 and 7, 2022. Commentary considers the bulk of the Day Two Agenda which conveyed an overall theme that NASH treatment is integrated and multifactorial. The day starts with Jeff Lazarus discussing Comprehensive Care Models for NASH, the path there and desired endpoints. The rest of Session 4 focuses on two forms of technical support: integrating non-invasive tests for NAFLD into clinical practices outside the liver space and looking at the power of apps to transform the weight management process. Session 5 focuses on pharmacotherapy, including use of current pharmacotherapy in weight loss and diabetes and some of the future agents that will come into use over the next few years. Finally, Session 6, which Roger Green will moderate, pulls together a diverse set of panelists to consider the NAFLD/NASH Roadmap in the context of social media and digital transformations. Listening to this conversation provides a clear sense of how broad the scope of Day Two issues will be.
In the interest of time, this summary does not list the names of the speakers giving each talk. This is an absolutely first-class global faculty. If you are curious, visit the meeting program to learn who these exceptional speakers are.
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For the first time, Surfing NASH takes a deep dive into the prospect of digital therapeutics, their ability to drive outcomes and the critical success factors for proper use and deployment. This is an increasingly apt topic which intermittently surfaces on the podcast but has never featured at the center of conversation. The Surfers are joined by Naim Alkhouri and two new guests with prominent focus in this space: Joe Rubinsztain, CEO and Co-Founder of ChronWell, and Mark Berman, CMO of Better Therapeutics.
In this final session, Roger prompts the panelists to share final thoughts around how digital therapeutics will evolve over time. Each offers a unique perspective accounting for different pieces of a collective puzzle: combating Fatty Liver through technological innovation. Joe and Mark discuss where they envision their respective work to converge. Jörn and Louise offer insights which indicate that different economic structures may require various reimbursement systems and provider dynamics. While this session features ideas around both the enormous potential and daunting challenges behind the world of digital health and digital therapeutics, the panelists provide rich insights which remain optimistic. These are big questions with far-reaching implications for the future of medicine. If you enjoy this topic and would like to learn more, we kindly invite you to leave a review on your preferred listening platform. We also encourage our audience to write us questions to include your on-ground experiences and ideas in the weekly discourse. Thank you for your continued support - stay safe and surf on!
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For the first time, Surfing NASH takes a deep dive into the prospect of digital therapeutics, their ability to drive outcomes and the critical success factors for proper use and deployment. This is an increasingly apt topic which intermittently surfaces on the podcast but has never featured at the center of conversation. The Surfers are joined by Naim Alkhouri and two new guests with prominent focus in this space: Joe Rubinsztain, CEO and Co-Founder of ChronWell, and Mark Berman, CMO of Better Therapeutics.
In this session, the group continues to discuss the benefits behind having an app where patients are in command of their wellness journey. Roger Green prompts Mark to further detail the Better Therapeutics product deployed in the feasibility study of cognitive behavioral therapy for improved liver health. Mark confirms that the product used was effectively the same which was used in their trial to demonstrate meaningful changes in blood sugar control for Type 2 diabetic patients. He reiterates the behavioral similarities that often underlie cardiometabolic conditions. Their thesis is that with the right support or therapy to address these behaviors, we can target multiple conditions simultaneously. Mark explains that the challenge therein lies in demonstrating from a regulatory perspective that this is an evidence-based form of prescriptive therapy.
Louise spurs comments around the idea that transparency in patient participation is enhanced when levels of comfort and trust for a process are high. She goes on to describe an app she is developing called MyLife365.me. This is a free lifestyle app that tracks how your daily life choices of food, drink and exercise impacts your liver health.
While this session features ideas around both the enormous potential and daunting challenges behind the world of digital health and digital therapeutics, the panelists provide rich insights which remain optimistic. These are big questions with far-reaching implications for the future of medicine. If you enjoy this topic and would like to learn more, we kindly invite you to leave a review on your preferred listening platform. We also encourage our audience to write us questions to include your on-ground experiences and ideas in the weekly discourse. Thank you for your continued support - stay safe and surf on!
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For the first time, Surfing NASH takes a deep dive into the prospect of digital therapeutics, their ability to drive outcomes and the critical success factors for proper use and deployment. This is an increasingly apt topic which intermittently surfaces on the podcast but has never featured at the center of conversation. The Surfers are joined by Naim Alkhouri and two new guests with prominent focus in this space: Joe Rubinsztain, CEO and Co-Founder of ChronWell, and Mark Berman, CMO of Better Therapeutics.
In this conversation, Joe details the inception of ChronWell and the company’s mission of assisting providers and insurers to deliver optimal care beyond the medical practice with teams empowered by scalable technology. These compounding ideas originate in the advent of electronic health records in the 90s. At the time, many failed to understand the utility in transitioning from paper to digital. Today, the potential of digital health burgeons with opportunity. Joe envisions a future where “computers are treating simple, delimited diseases in a well designed pathway which is augmenting the ability of a doctor to deliver.” He goes on to discuss the role of insurers in this future and explains the nuances which align ChronWell’s identity as a digital platform. Jörn Schattenberg commends the term “augment” because of the need to leverage all tools available in identifying the swathes of unmet patients.
Joe highlights that ChronWell is partnering with both primary care providers and specialists to build understanding around the full spectrum of disease. When considering new generation tools to treat conditions like NAFLD and NASH, he asserts that “we need to think broadly about activating the ecosystem” and removing any friction for the health care provider to utilize. This leads Naim to comment on the importance of still striving to find solutions for all Fatty Liver patients and not just those with clinically significant fibrosis.
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If you enjoyed this episode and would like to learn more about digital therapeutics, we kindly invite you to leave a review on your preferred listening platform. We also encourage our audience to write us questions to include your on-ground experiences and ideas in the weekly discourse. Thank you for your continued support - stay safe and surf on!
Stay Safe and Surf On!
For the first time, Surfing NASH takes a deep dive into the prospect of digital therapeutics, their ability to drive outcomes and the critical success factors for proper use and deployment. This is an increasingly apt topic which intermittently surfaces on the podcast but has never featured at the center of conversation. The Surfers are joined by Naim Alkhouri and two new guests with prominent focus in this space: Joe Rubinsztain, CEO and Co-Founder of ChronWell, and Mark Berman, CMO of Better Therapeutics.
Naim leads this conversation by elaborating on his involvement in a feasibility study with Better Therapuetics on use of Cognitive Behavioral Therapy for improving liver health. Mark and his team partnered with two of Naim’s clinics to conduct the study over the course of three months. Their aim was to recruit participants from a specialty clinic setting who exhibit a range of Fatty Liver disease states and develop data to understand the effects of their therapies on the liver and cardiometabolic condition. Naim discusses why they chose targeting MRI-PDFF as a primary outcome measure. He explains that while a 90-day window is restrictive in terms of identifying fibrosis improvement, changes in AST and ALT were examined in addition to analysis of FibroScan metrics. It’s noted that increased engagement with the app correlated with improved weight and liver enzyme values. Naim goes on to share ideas around implementing combination therapies which harness the unique utility of digital apps with agents like resmetirom or semaglutide. From here, the session opens up to impressions and questions of the other panelists. Jörn Schattenberg highlights quality of life as a valuable endpoint and Louise comments on the benefit behind what’s described as a “non-medical” approach where patients are in command of their wellness journey. Roger Green asks Mark to expand on the premise and deployment of Better Therapeutic’s curated cognitive behavioral therapy.
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If you enjoyed this episode and would like to learn more about digital therapeutics, we kindly invite you to leave a review on your preferred listening platform. We also encourage our audience to write us questions to include your on-ground experiences and ideas in the weekly discourse. Thank you for your continued support - stay safe and surf on!
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For the first time, Surfing NASH takes a deep dive into the prospect of digital therapeutics, their ability to drive outcomes and the critical success factors for proper use and deployment. This is an increasingly apt topic which intermittently surfaces on the podcast but has never featured at the center of conversation. The Surfers are joined by Naim Alkhouri and two new guests with prominent focus in this space: Joe Rubinsztain, CEO and Co-Founder of ChronWell, and Mark Berman, CMO of Better Therapeutics.
In this conversation, Joe and Mark detail their backgrounds and respective roles at two leading digital therapeutics companies. Both Joe and Mark are physicians by training with unique interests which led them down fascinating paths. Joe discloses he is a “computer scientist at heart.” Mark shares that he has always had a passion for nutrition and behavior change. Mark goes on to elaborate on his work today, underscoring a fundamental idea at the foundation of Better Therapeutics. Much of cardiometabolic diseases - including NAFLD - is rooted in behavior. While both primary care and specialty clinics absorb the consequences, neither is adequately equipped to facilitate society-wide behavioral change. Better Therapeutics exists to answer this dilemma by developing forms of what's called Prescription Digital Therapies. Representing a new treatment modality, the use of digital therapeutics under physician supervision can enable digitally-delivered behavioral therapy that is prescribed, reimbursed and accessible to patients in need through the use of a smartphone. Last year, the company announced positive results of a pivotal trial in Type 2 diabetes which demonstrated the use of a Prescription Digital Therapeutic to have clinically meaningful changes in blood sugar control. The company has also expanded its efforts by applying Prescription Digital Therapeutics to combat the swelling burden of NAFLD and NASH. To do so, Mark and his team partnered with two of Naim’s clinics to conduct a feasibility study over the course of three months. Their aim was to recruit participants from a specialty clinic setting who exhibit a range of Fatty Liver disease states and develop data to understand the effects of their therapies on the liver and cardiometabolic condition. Targeting MRI-PDFF as a primary outcome measure, the topline results revealed that the majority of patients were able to demonstrate improved liver health.
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If you enjoyed this episode and would like to learn more about digital therapeutics, we kindly invite you to leave a review on your preferred listening platform. We also encourage our audience to write us questions to include your on-ground experiences and ideas in the weekly discourse. Thank you for your continued support - stay safe and surf on!
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For the first time, Surfing NASH takes a deep dive into the prospect of digital therapeutics, their ability to drive outcomes and the critical success factors for proper use and deployment. This is an increasingly apt topic which intermittently surfaces on the podcast but has never featured at the center of conversation. The Surfers are joined by Naim Alkhouri and two new guests with prominent focus in this space: Joe Rubinsztain, CEO and Co-Founder of ChronWell, and Mark Berman, CMO of Better Therapeutics.
Among a plethora of discussion points unpacked, the panelists explore the following major themes:
09:24Mark is first to elaborate on his work and underscores the big idea at the foundation of Better Therapeutics: much of cardiometabolic diseases - including NAFLD - is rooted in behavior. While both primary care and specialty clinics absorb the consequences, neither is adequately equipped to facilitate society-wide behavioral change. Better Therapeutics exists to answer this dilemma by developing forms of what's called Prescription Digital Therapies. Representing a new treatment modality, the use of digital therapeutics under physician supervision can enable digitally-delivered behavioral therapy that is prescribed, reimbursed and accessible to patients in need through the use of a smartphone.
15:25Better Therapeutics has recently focused on applying Prescription Digital Therapeutics to combat the swelling burden of NAFLD and NASH. In doing so, their team partnered with two of Naim's clinics to conduct a feasibility study. Naim elaborates on quantifying the analysis of that study. While a 90-day window is restrictive in terms of identifying fibrosis improvement, changes in AST and ALT were examined in addition to analysis of metrics provided by FibroScan. Naim shares ideas around implementing combination therapies which harness digital apps and agents like resmetirom or semaglutide. From here, conversation opens up to impressions and questions from the panelists. Jörn Schattenberg highlights quality of life as a valuable endpoint and Roger Green asks Mark to expand on the premise and deployment of cognitive behavioral therapy.
26:02Joe details the inception of ChronWell and the company’s mission of assisting providers and insurers to deliver optimal care beyond the medical practice with teams empowered by scalable technology. He envisions a future where “computers are treating simple, delimited diseases in a well designed pathway which is augmenting the ability of a doctor to deliver.” He goes on to discuss the role of insurers in this future and explains the nuances that align ChronWell’s identity as a digital platform.
37:24The group discusses the benefits behind having an app where patients are in command of their wellness journey. Louise spurs comments around the idea that transparency is enhanced when levels of patient comfort and trust with a process are high. She goes on to describe facets of an app she is developing called MyLife365.me. This is a free lifestyle app that tracks how your daily life choices of food, drink and exercise impacts your liver health.
46:00Finally, Roger prompts the panelists to share final thoughts around the future of this space. Each offers a unique perspective accounting for different pieces of a collective puzzle: combating Fatty Liver through digital health. If you enjoy the episode or have questions on this subject, we kindly ask that you submit reviews wherever you download our discussions. Alternatively, you can write us directly at questions@SurfingNASH.com.
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This week's episode From the Vault comes from Season 2, Episode 59.3. Lead author Jeffrey Lazarus and co-author Jörn Schattenberg join Stephen Harrison, Louise Campbell, and Roger Green to discuss the groundbreaking paper “Advancing the Global Health Agenda for NAFLD.” This conversation focuses on what will happen now, why NAFLD is “the canary in the coal mine,” and how we can combine strengths in different parts of the world to make all of our programs more robust.
For Jeff, “what’s next” includes a third, smaller Delphi study as well as a greater focus on Sustainable Development Goals (SDGs) around environment and possible diet. As it continues, Stephen discusses ways to persuade patients (and perhaps societies?) to change habits, practices and beliefs radically to fight this disease. Louise returns to the issue of SDGs to discuss how advocates can leverage the increasing volume of liver cancer patients to represent larger related issues, which leads Jeff to comment on how prevalent and costly liver cancer is today, compared to other cancers. In the end, Stephen recommends a two-item impact strategy: clear messages supported richly through large, high-impact multimedia campaigns.
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In the final conversation on AASLD’s new practice guidance, Roger Green contextualizes a new project he is embarking on with Ken Cusi. Together as co-hosts, they will be debuting a new podcast series from next week titled The NASH Tsunami in Diabetes: Getting Ahead of the Rising Tide. The content featured will largely be targeted toward healthcare professionals who treat diabetic patients, the patients themselves and their caregivers. The NAFLD-diabetes dual prevalence is alarmingly high:
- 15% of diabetic patients may have fibrosis
- In one study, 70% of diabetics had fatty liver and 35% had NASH
- 25% of deaths in people with NAFLD are related to cardiovascular disease
- NAFLD is an independent risk factor for development of diabetes, cardiovascular and chronic kidney diseases
After the group exchanges comments around this exciting news, conversation shifts back toward the practice guidance. Louise Campbell notes approvingly of its array of considerations which include polycystic ovary, menopause, testosterone alteration and the thyroid to name a few. She goes so far as to describe its succinct qualities as “one of the best written guidance documents I think I've ever read.” Jörn Schattenberg adds his appreciation for the inclusion of some high level hepatology concepts around histology and cell ballooning. Roger compares this documentto the new generation of hard-cover suitcases that can appear sleek and compact while in fact being stuffed full of important, neatly organized materials.After which, he prods the group in a final question focused on the greatest practical impact of this guidance in the next couple of years. Louise believes it may be the document that strikes the ultimate chord in raising awareness in primary care: “It’s readable, it's digestible and it's implementable.” Jörn reckons the document is a strong step toward embracing multidisciplinary models of care where the NAFLD patient sits at the intersection of many different disciplines. Ken follows with a sizeable wishlist and offers an apt final comment: “If a dream comes true in a lifetime, you didn't dream big enough.” Surf on to discover these thought-provoking final insights.
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Late last week, AASLD published new practice guidance on the clinical assessment and management of NAFLD. The Surfers convene with Ken Cusi, who contributed to the previous iteration published in 2018, to explore its key features and implications. The updated document reflects the many advances pertinent to any practitioner caring for patients with NAFLD. This conversation focuses around the influence the guidance imparts outside of the US.
Jörn Schattenberg shares that an EASL guideline commission has been set forward which will refer to the AASLD guidance in supporting its development. Louise comments on the density of information made available through the guidance, commending its extensive list of references. She expresses concern that NICE will not tap into what’s available here by remaining restricted to data obtained exclusively within the UK. She goes on to advocate for the enormous potential in constructing a guideline that collectively harnesses the “masses of evidence” available in the different guidances emerging throughout the world. When Roger Green asks whether this will be possible, Louise suggests that NICE might be headed in a less insular direction and cites the approval of FibroScan in primary care settings as a recent “leap of faith.” Lastly, she discusses her desire for an investigation into the dynamics of CAP scores to be included in these documents. Jörn agrees and adds that CAP ultimately provides a barometer for metabolic health. At the end of the session, Ken circles these ideas back to the importance behind screening in at-risk populations.
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Late last week, AASLD published new practice guidance on the clinical assessment and management of NAFLD. The Surfers convene with Ken Cusi, who contributed to the previous iteration published in 2018, to explore its key features and implications. The updated document reflects the many advances pertinent to any practitioner caring for patients with NAFLD. This conversation focuses on the impact this guidance may have on patients: will it make a difference and if so, how?
Ken asserts his position that both patients and providers need to be educated on solutions available today. Measures range from effective diet modifications to bariatric surgery and anti-obesity drugs. Louise Campbell reminds that not all patients interact with physicians and that nurses, dieticians and other allied health professionals experience more numerous contact points in terms of co-morbidity management. She asserts that guidances and guidelines need to make an effective impression on the frontline professionals, caretakers and even the patients themselves. This prompts Ken to share some exciting news with regards to the ADA formally recognizing NASH as a problem associated with diabetes. He reveals that he is chairing a committee which will work to create a consensus statement on this subject through consulting an array of stakeholders. Notably, they are inviting the participation of dieticians, diabetes educators, pharmacy representatives, obesity management leaders, primary care representatives and hepatologists among other groups. Ken expresses his optimism for the momentous energy and convergence of fields in an unprecedented effort to collectively combat Fatty Liver diseases. Jörn adds that such collaboration will drive stronger patient advocacy and better education around what specific questions they should be asking their treaters.
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Late last week, AASLD published new practice guidance on the clinical assessment and management of NAFLD. The Surfers convene with Ken Cusi, who contributed to the previous iteration published in 2018, to explore its key features and implications. The updated document reflects the many advances pertinent to any practitioner caring for patients with NAFLD. This conversation introduces ideas around how the guidance describes use of biomarkers and NITs to either exclude advanced disease or identify those with a high probability of fibrosis.
Roger Green begins by recalling how the US addressed cholesterol 35 years ago. Reference labs were asked to change what was considered the normal value of cholesterol from two standard deviations above the mean down to a fixed number. This anecdote draws a parallel to the duality facing ALT. He suggests a lower high standard of 30U/L rather than 40U/L could be used, but recognizes that it might not be of benefit to emphasize ALT if patients with normal liver function also have NAFLD. He asks the panelists for their ideas around how we balance these issues to bring ALT into perspective. Jörn Schattenberg notes that typically the upper limit of normal is defined based on the reference population of where the test is evaluated. For example, his hospital in Mainz uses 50U/L on the basis of their reference population. Jörn explains that if this number is changed, an influx of abnormal tests will change the dynamics and economics of patients referred for suspected liver disease. On the other hand, reevaluating cut off points is relevant because patients with normal ALTs are far less likely to be investigated in terms of liver disease. His main takeaway: the guidance demonstrates that the advanced fibrosis disease stage would greatly benefit from the utility of FIB-4. Using this test at a large scale is sufficient and ultimately something to build on. Ken adds that the guidance has aimed to improve the sensitivity of FIB-4 in regards to false positives. He looks forward to the near future of increased precision where the right patients are appropriately referred to clinicians.
Roger notes that as a guidance document in the context of primary care, having three to four statements around ALT might be slightly confusing. He refocuses on the question of whether reference labs have a role in creating clarity around this issue. From a European perspective, Jörn suggests education is needed to drive the question from the physician to the lab. Ken points out that the US electronic medical record system should be able to integrate notifications around cut offs. Louise Campbell asserts the need for AST and ALT to be universally included within blood profiles. At the moment, this is not standard in many countries outside of the US. She harkens back to the potential AI has in the future of automated data analysis, but the essential first step is to ensure tests are able to be computed. In the final comment of this conversation, Ken reiterates the importance of recognizing and driving the message of harnessing what’s readily available today to positively influence the natural history of patient disease.
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Late last week, AASLD published new practice guidance on the clinical assessment and management of NAFLD. The Surfers convene with Ken Cusi, who contributed to the previous iteration published in 2018, to explore its key features and implications. The updated document reflects the many advances pertinent to any practitioner caring for patients with NAFLD. This conversation introduces differentiating factors which define a Guidance document versus Guidelines.
The conversation starts with Ken introducing the new guidance by placing it in the context of the last five years of thinking about screening and treatment of Fatty Liver patients. He highlights significant events including both let downs in terms of drug development and the emerging optimism surrounding new candidates in the NASH therapeutics pipeline. He notes that this guidance offers an affirmative consensus on the screening of patients with Type 2 diabetes - a contentious topic for the committee Ken participated in formulating the preceding guidance. In this initial high-level overview it already becomes evident that the new practice guidance is comprehensive in a myriad of applications, presaging it to be a highly effective resource.
Jörn Schattenberg joins to voice his initial impression and suggests this document offers an excellent viewpoint as to how the field is moving forward. He points to Table 7 - a summary of key concepts to guide clinical practice - as a particularly comprehensive point of reference for the latest recommendations. Roger Green also commends Table 7, highlighting four bullet points embedded which are dubbed Pearls for the assessment of NAFLD:
- Aminotransferase levels are frequently normal in patients with advanced liver disease due to NASH and should not be used in isolation to exclude the presence of NASH with clinically significant fibrosis.
- Normative values for ALT reported by most laboratories exceed what is considered a true normal. As a general rule, ALT >30 U/L should be considered abnormal.
- Although standard ultrasound can detect hepatic steatosis, it is not recommended as a tool to identify hepatic steatosis due to low sensitivity across the NAFLD spectrum.
- CAP as a point-of-care technique may be used to identify steatosis. MRI-PDFF can additionally quantify steatosis.
Ken notes that this document will “rectify some confusion from past guidelines." Specifically, it holds special value for primary care professionals who may not be familiar with the field but whose role is expected to grow dramatically over time. One key point: the role of front-line treaters will not be simply to screen for fat in the liver, but to identify patients in high-risk subgroups with clinically significant fibrosis. He notes that we can support these patients today through a combination of lifestyle interventions and currently available anti-obesity and diabetic medications.
As the session winds down, Jörn previews more detailed discourse around follow-up data on NITs and how best to establish evidence for progressing patients. Lastly, Louise Campbell adds her ideas on using this document to further support and develop local pathways and areas of care. In example, she would like to see updated guidelines from NICE following access to FibroScan in the community setting.
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Late last week, AASLD published new practice guidance on the clinical assessment and management of NAFLD. To explore its key features and implications, the surfers convene with Ken Cusi, who contributed to the previous iteration published in 2018. The updated document reflects the many advances pertinent to any practitioner caring for patients with NAFLD. Notably, and as detailed in this episode, it emphasizes advances in noninvasive risk stratification and therapeutics. The group covers at-depth a range of topics to underscore the basis of progress in the field while offering compelling insights on the emerging path forward in combating Fatty Liver diseases.
Among a plethora of other discussion points unpacked, the panelists expand on the following major themes:
06:21
Roger Green opens by asking Ken to highlight how a Guidance differs from a Guideline. Ken goes on to provide a robust introduction that contextualizes this publication and states "a lot has happened in five years." Jörn Schattenberg and Louise Campbell follow with their initial impressions, each commending what they describe as an excellent framework for moving the field forward.
15:24The panelists dive into the guidance’s account of using biomarkers and NITs to either exclude advanced disease or identify those with a high probability of cirrhosis. They focus mainly on the utility of FIB-4 and the dynamics of ALT cut points. Louise comments on the universal importance of including AST and ALT in blood profiles.
24:01Conversation shifts toward the impact this guidance may have on patients: will it make a difference and if so, how? Ken outlines options for treating patients today and drives a critical message: “the time is now.”
31:39Jörn and Louise discuss what sort of impact the AASLD guidance may have outside of the US. While Jörn notes the utility of this document for developing EASL guidelines, Louise is wary that NICE will remain restricted to referencing data obtained exclusively within the UK.
38:15As the session winds down, Roger announces that Ken will be co-hosting a new podcast series with him. The NASH Tsunami in Diabetes: Getting Ahead of the Rising Tide is tailored for healthcare professionals who treat diabetic patients, the patients themselves and their caregivers. Finally, Roger returns to one last question centered around the guidance: how will this shape progress in coming years?
If you enjoy this episode or have questions on the new guidance, we kindly ask that you submit reviews wherever you download our discussions. Alternatively, you can write us directly at questions@SurfingNASH.com. We also encourage our audience to explore more on the Rising Tide series before it airs next week. Most important of all, we whole-heartedly thank you for your continued support as we set out to put a major dent in Fatty Liver disease in 2023 and beyond.
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The entire Fatty Liver community benefits from NASH Patient Advocacy and the work of our advocates, but relatively few of us understand what advocates do or how we benefit from their work. Leading German patient advocate Achim Kautz and Global Liver Institute Vice President of Policy and Public Affairs Andrew Scott discuss how they came to Fatty Liver patient advocacy, their priorities and activities that support our community, and the unique challenges of their fascinating work.
This conversation From the Vault winds up focusing on two key areas to focus future organizing and advocacy. The first is to think locally. Achim and Andrew point out that they can find success working with local and regional governments and then build up from this success to a national discussion. The second is clear, consistent communication between all stakeholders in the Fatty Liver community and between the community and the payers and government forces we need to persuade.
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If you enjoy these episodes, we kindly ask you to leave a review on your preferred listening platform. We also encourage our audience to write us questions to include your on-ground experiences and ideas in the weekly discourse. Most important of all, we whole-heartedly thank you for the continued support as we set out to put a major dent in Fatty Liver disease in 2023 and beyond. Stay safe and surf on!
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In an introduction to Fatty Liver in Australia, Louise Campbell is joined by Tony Rahman, Director of Gastroenterology & Hepatology at The Prince Charles Hospital in Brisbane and Adjunct Professor in the College of Medicine and Dentistry at James Cook University.
Louise leads this final conversation by highlighting the prospect of imminent drug approvals in the Fatty Liver space. She asks Tony for impressions on Australia’s positioning to identify its patient population and its ability to distribute limited resources in response to accessing expensive new drugs. Tony describes the approval pathway in Australia and suggests that the ultimate challenge will involve finding what he terms the “hidden cohorts” of patients who would benefit from these drugs. This will take time and money. Louise points to the Predictive Health Intelligence project outlined in S4E5, which sounds promising but will be challenged by Australia’s lack of state-of-the-art electronic records. Tony hopes within the next ten years this can be an area of massive improvement.
The last part of this discussion focuses on the future of Fatty Liver for Australia. Louise asks for what Tony envisions in the next 2-3 years for the field. Tony first highlights optimism around use of semaglutide and other GLP-1s as a major wall of defense. He then looks to the mission of driving education in public health and for hepatology and gastroenterology societies to heavily petition for the fact that NAFLD and NASH is an escalating dilemma in need of addressing now.
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In an introduction to Fatty Liver in Australia, Louise Campbell is joined by Tony Rahman, Director of Gastroenterology & Hepatology at The Prince Charles Hospital in Brisbane and Adjunct Professor in the College of Medicine and Dentistry at James Cook University.
Louise starts this conversation with an anecdote from her experiences in Australia providing virtual clinics to those living 6 to 10 hours drive away from their nearest consultation. She follows with a question to Tony on whether GPs want to buy into NAFLD and NASH in the same way that they responded to successful Hepatitis C programs. Tony replies yes, but alludes to some challenges in doing so. He notes the influence of how a problem and solution are presented has on the uptake of interest and whether the benefits posed are considered worthwhile. He explains that GPs in Australia are paid per patient and time away for education can be perceived as a loss of income. He suggests that rather than solely “bombarding GPs with education,” change will more readily be adopted if there is a robust plan in place. Conducting various environmental tests - even as simple as a GP focus group - considerably improves uptake of a newly introduced initiative. He continues on to describe a traffic light system adopted by the Prince Charles Hospital that utilizes FibroScan to assess the likelihood of a patient to develop liver disease in a given time. Louise comments on the importance of seeking constant refinement in establishing such systems.
Discussion shifts to the topic of guidelines and use of FIB-4 in the primary care setting. Louise asks whether use of FIB-4 is a part of any Australian protocol and, if not, is there any traction for its positioning as a readily available tool for risk stratification. Tony maintains it is making headway along with calculating an AST to Platelet Ratio Index (APRI), a popular measurement in the efforts of moving patients along Hepatitis C treatment. Today, he is wary that GPs who are seeing a large number of patients may not have the time or prioritize making calculations. At this point, Louise points to the idea of joint referrals in light of emerging recommendations from the cardiology community on risk assessment of NAFLD. She notes the combined uptake of FIB-4 and FibroScan as something potentially valuable to an initiative such as Heart of Australia. Tony points out that establishing convincing clarity around the links between Fatty Liver disease and cardiovascular outcomes is conducive to the protocol-led Australian doctors. At the end of the session, Tony illustrates potential challenges in Australia not having a FibroScan medicare billing code and comments on factors which affect accessibility.
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In an introduction to Fatty Liver in Australia, Louise Campbell is joined by Tony Rahman, Director of Gastroenterology & Hepatology at The Prince Charles Hospital in Brisbane and Adjunct Professor in the College of Medicine and Dentistry at James Cook University.
This conversation starts with Louise asking about the prevalence and composition of Australia’s Fatty Liver population. Specifically, she wonders what percent of this group are Aboriginal peoples. Tony suggests that while the data is scarce, an ongoing project on diabetes with James Cook University has recruited a cohort of First Nations patients. Within this cohort, it has been determined that instances of Fatty Liver disease are “moderately high.” He expands focus to the whole of Australia, citing the Australian Institute of Health and Welfare which reports an alarming rise in prevalence. The country is estimated to skyrocket from a quarter of the population having NAFLD to as high as 40% by 2030. Tony casts doubt on the accuracy of these numbers and suggests that prevalence is likely to be much higher already due to rates of obesity.
Louise notes that during her most recent visit to Australia, she found high liver fat in roughly one-third of an 80-person cohort that came from “relatively high socioeconomic background" and considered itself “relatively fit and healthy.” More alarming to her, all of the 9% of patients with elevated liver stiffening were postmenopausal women.
The remainder of the conversation focuses on a program Tony contributes to called Heart of Australia, the country’s first mobile medical program delivering specialist services to regional and remote communities. He explains the inception of the initiative and how he helped to introduce FibroScan as a part of its services. Again, this program focuses on roughly 7 million people - 28% of Australia’s population - who live in rural or remote areas. The session concludes with Louise’s comments on the importance of delivering health care solutions to these populations by expanding accessibility to services and promoting education on liver health.
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In an introduction to Fatty Liver in Australia, Louise Campbell is joined by Tony Rahman, Director of Gastroenterology & Hepatology at The Prince Charles Hospital in Brisbane and Adjunct Professor in the College of Medicine and Dentistry at James Cook University.
This opening conversation starts by following the path that took Tony from his training in London and his Doctor of Philosophy in Medicine from Imperial College to his work in Australia today. Tony asserts that he has been fortunate to be part of a generation which has seen sweeping progress in the treatability of Hepatitis C and goes on to discuss how to apply this experience to the onslaught of liver disease that Australia is grappling with today. An important theme of the extended episode emerges: Australia faces considerable and unique challenges associated with providing for large, rural-based populations. As the subsequent conversations unfold, the duo explore various approaches to serving this community that comprises 7 million people, or around 28% of Australians. In this session, Tony previews telehealth solutions and a traffic light system oriented toward serving this subpopulation. He notes that with these remote measures in place, the patients physically presenting for consultation are distilled to those with progressed Fatty Liver diseases. Finally, an interesting trend is underscored: the alcohol-related cohort is shrinking and the last ten years has paid increasing attention to refining available tools to provide for an alarming surge in NAFLD and NASH.
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This week on the podcast, Louise Campbell leads the Surf in a one-on-one interview with Tony Rahman on what’s happening for Fatty Liver in Australia. Tony is the Director of Gastroenterology & Hepatology at The Prince Charles Hospital in Brisbane and Adjunct Professor in the College of Medicine and Dentistry at James Cook University. The episode begins with an introduction to Tony's career, outlining a journey of how he became involved in fighting Fatty Liver disease.
Louise leads by investigating the uncertainties around prevalence of NAFLD and NASH in Australia. Not only is it unclear exactly how many people have Fatty Liver there, but also who comprises this total population. Specifically, she wonders what percent of this group are Aboriginal peoples. While his personal experience at one hospital does not lend perspective to this question, Tony points to an ongoing project on diabetes with James Cook University. A considerable cohort of First Nations patients were recruited and it was determined that instances of Fatty Liver disease in this group were “moderately high.” In terms of the whole of Australia, Tony underscores insights from the Australian Institute of Health and Welfare which reports an alarming rise in prevalence. It is estimated that the country will increase from 20-25% of a population with NAFLD to as high as 40% by 2030. Tony casts doubt on the accuracy of the current numbers, suggesting that prevalence is likely to be much higher already due to rates of obesity. He adds that with a broadened definition from NAFLD to MAFLD, the inclusion of those who are not overweight but possess other metabolic risk factors will only surge figures higher yet.
Focus next shifts to a program Tony contributes to called Heart of Australia, the country’s first mobile medical program delivering specialist services to regional and remote communities. He explains the inception of the initiative and how he helped to introduce FibroScan as a part of its services. Around 7 million people - 28% of Australia’s population - live in rural or remote areas. Louise comments on the importance of delivering health care solutions to these populations and expanding accessibility and promoting education. She draws comparison to her own experiences working remotely in Australia to provide virtual clinics to those living 6 to 10 hours drive away from their nearest consultation. When asked whether GPs want to buy into NAFLD and NASH in the same way that they responded to Hepatitis C programs, Tony says yes. He notes the influence of how a problem and solution are presented has on the uptake of interest and whether the benefits posed are considered worthwhile. GPs in Australia are paid per patient and time away for education can be a loss of income. He suggests that rather than solely “bombarding GPs with education,” change will more readily be adopted if there is a robust plan in place. He goes on to explain a traffic light system adopted by the Prince Charles Hospital that utilizes FibroScan to assess the likelihood of a patient to develop liver disease in coming years. The main takeaway: establishing a good model requires refinement.
As the session winds down, they continue on to explore the role of FIB-4 in Australia and the link between Fatty Liver disease and cardiovascular outcomes. This leads to ideas around private versus public sector health care dynamics and creating equitable access to FibroScans. Lastly, Louise and Tony consider the prospect of a drug approval and whether Australia is prepared to identify the patients most in need.
If you enjoy this episode, we kindly ask that you submit a review wherever you download our weekly discourse. Thank you for listening, stay safe and surf on!
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One of the most important challenges facing Fatty Liver stakeholders involves improving early diagnosis for patients with clinically relevant or advanced fibrosis (F2/3). Today, a significant percentage of patients learn they are living with cirrhosis in the Emergency Department during a decompensating event. Four in ten of these patients in the UK do not leave the hospital. In this episode From the Vault, panelists review a model that Ian Rowe and Richard Parker developed to determine the most cost-effective strategy for F2/3 diagnosis.
As this conversation starts, Louise Campbell notes that John Dillon reported in Barcelona that slightly over half of patients identified as having Fatty Liver via iLFT never returned for their appointments. Ian Rowe points out that this will reduce the costs in the model due to missed diagnoses but questions whether this cost reduction is truly beneficial since missed patient visits translate into non-treatment. More important, he reminds us that iLFT is under constant improvement so that data collected earlier in its lifecycle might not accurately reflect its costs and benefits today.
Upon Roger Green’s invitation for other questions Louise Campbell asks whether “we” (presumably the UK NHS) should do a better job supporting positive diet and exercise activity for healthcare professionals inside the system. On a more serious note, this leads Ian and Louise to focus on the policy issues that can support patients better (particularly those in the workforce). Ian points out that alcohol is issue #1 for many of these patients. He and Louise go on to point out the importance of public policy around things like soda and sweet food advertising in shifting consumers’ focus or craving for bad foods. Roger suggests that this is a two-element issue: stopping advertising for soda and sweets will reduce disease over time but we also need to treat patients who already have developed disease. As he puts it, policy can “put your foot on the hose,” but even if we stop the in-flow of new Fatty Liver and metabolic patients, we still have “the patients in the hose” and they will need therapy.
As a final thought before wrap-up, Ian shares his belief (which Louise also holds) that VCTE might be more effective in causing changes in patient behavior than blood tests, even if they point up the exact same patient need. The difference: feedback from VCTE comes in real-time where patients get face-to-face feedback and respond, whereas bloodwork results comeback to the patient several days later and delivered impersonally.
From here, the group moves to the wrap-up question, which addresses research we should be doing and action steps/changes in behavior we should be promoting.
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Surfing NASH is joined by Tim Jobson, Co-founder of Predictive Health Intelligence, to discuss a system by which historic blood test results are combined and analyzed to flag patients in need of intervention. This wrap-up conversation revisits many of the same themes explored in the preceding sessions: data aggregation, data transparency and patient enthusiasm to name a few. An important note emerges from Roger Green. He suggests that such an enormous initiative does not have to be thought of as exceedingly complicated. Instead, this project could be conceptualized as taking action on the complex task of organizing vast quantities of data. There is a need to account for, align, compute and otherwise use and test the existing data in pursuit of improving patient care.
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To learn more about Tim and Predictive Health Intelligence, be sure to visit their website. If you enjoyed this episode, we kindly ask you to leave a review on your preferred listening platform. We also encourage our audience to write us questions to include your on-ground experiences and ideas in the weekly discourse. Most important of all, we whole-heartedly thank you for the continued support as we set out to put a major dent in Fatty Liver disease in 2023 and beyond.
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Surfing NASH is joined by Tim Jobson, Co-founder of Predictive Health Intelligence, to discuss a system by which historic blood test results are combined and analyzed to flag patients in need of intervention. This conversation begins with focus on the dual issues of patient data and proactivity. Roger Green states that “the careful and intelligent use of early data to empower patients to know when to ask about their own health” should yield a myriad of benefits. Louise Campbell agrees and comments on how patients feel when the system is proactively supporting them. Louise then asks what happens when the system produces an inaccurate diagnosis. Tim notes that this system provides data to clinics so that they can make the decisions. This minimizes the chance of systematic error and discourages autonomic reliance while still supporting patients in self-managing their health.
The conversation continues on the issue of patient data, concluding with Roger’s observation that the passionate belief in protecting data is half-right. He reasons that patients (like all people) favor protected data against those who would take advantage of it. However, most are comfortable with affording accessibility to those who use their data to improve patients’ health and general life.
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Surfing NASH is joined by Tim Jobson, Co-founder of Predictive Health Intelligence, to discuss a system by which historic blood test results are combined and analyzed to flag patients in need of intervention. This conversation starts with a dialog between Tim and Roger Green around how simple the data and computations in this system appear to be. Roger describes a benefit in terms of patient throughput and asks whether Predictive Health has investigated along these lines. Tim agrees with the assumption but indicates that this work has yet to be accomplished. Finally, he underscores that this tool can help locate and recruit patients for research studies. Jörn Schattenberg agrees with the idea before asking whether the system processes natural language, or in his anecdote, scraps of paper from years ago found in the patient file. Tim suggests this to be easy enough to execute within the system and will become more powerful as use of the system expands.
From here, the conversation shifts to patient reactions. Tim notes that, in general, reactions have trended universally positive. Specifically, patients do not seem concerned that the health system has their identified data, something vastly different from what administrators believe and say. As the conversation winds down, Roger asks Jörn how he feels this work will align with the clinical care pathways initiative he is spearheading with Jeff Lazarus. Jörn confirms it will align well, indeed.
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Surfing NASH is joined by Tim Jobson, Co-founder of Predictive Health Intelligence, to discuss a system by which historic blood test results are combined and analyzed to flag patients in need of intervention. This conversation starts with Jörn Schattenberg asking questions around the underlying system and whether the algorithm is “plastic?” This is based on the set of conditions that the algorithm has to exist with missing data and that what is missing may vary from patient to patient. In addition to these conditions, analysis has to be time-sequenced. In response, Tim dives into the details of how these things actually work within this Predictive Health system. Specifically, he comments on how simply looking at ALT and platelet levels longitudinally can improve overall patient assessment by exceptionally large margins.
Louise Campbell joins to commend the system and ask Tim whether there is pressure to utilize less often to save money. Tim explains that his team is running a full economic analysis to demonstrate massive potential savings the NHS can yield by adopting this system upfront rather than dealing with the financial burden of treating downstream disease progression. Interestingly, it seems health administrators in his region seem to feel the same way, at least intuitively. The rest of the session goes on to address questions around measuring impact and explore simple ideas around how to execute this technology and its processes.
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Surfing NASH is joined by Tim Jobson to discuss what he describes as a “combined informatics and clinical program simultaneously.” In this conversation, Tim begins by describing his background and how he came to partner with expert clinicians and specialists in healthcare IT to address how we can better identify liver patients in need of intervention. In partnership with former colleague Neil Stevens and his local NHS Trust, Tim led a grant application that gave rise to Predictive Health Intelligence where he holds the roles of Medical Director and Chief Investigator. Tim expounds the journey of improving understanding around how patients with liver disease could be diagnosed earlier by accessing and combining the results of previous blood tests. There are thousands of patients in any given region in the UK who have taken blood tests in multiple, unconnected offices. The system which Tim is working on aggregates a large number of these blood tests and searches for patterns in individuals. If a target pattern presents, the patient is summoned for a visit which can lead to treatment or an intervention.
Jörn Schattenberg is the first co-host to share an impression. His two questions: whether they are looking at earlier stage patients and what have been the flavors of patient responses? Surf on to hear Tim’s response.
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Surfing NASH is joined by Tim Jobson, founder of Predictive Health Intelligence, to discuss applying analytics to sieve through and distill invaluable data otherwise dormant in the NHS record systems. Tim, a Consultant Gastroenterologist and Fellow of the Royal College of Physicians, has firsthand experience with the shortcomings and frustrations around undiagnosed liver disease. Illustrating the pursuit of a solution, he walks us through the journey of developing a simple tool that can identify patients at risk of liver disease by analyzing the results of blood tests given throughout their lives. Also featuring in this session are Surfers Jörn Schattenberg, Louise Campbell and Roger Green, who pose compelling questions and share insightful perspectives on this particularly pertinent subject to the podcast.
Tim begins by providing his background and how he came to partner with expert clinicians and specialists in healthcare IT to address how we can better identify patients. A pivotal validation came in the form of funding from the National Institute for Health Research to establish Predictive Health Intelligence and create a software and system that works quickly and straightforwardly. He notes that this project is a “combined informatics and clinical program simultaneously,” where the building of new clinical pathways is a key part of their process and aims. An important idea emerges: instead of waiting for inbound referrals, Tim is focused on how to proactively engage in outreach to those who likely may not come to attention until presenting with decompensated cirrhosis. At this point, the challenge around collecting patient data is acknowledged but explored in more detail later in the conversation. Once approved, the task targets organizing, curating and systematizing this data in a way that enables end users to search for, identify and investigate patterns of blood tests. This approach offers tremendous value in its ability to analyze cumulative results as opposed to deriving insights from a single point in time. By demonstrating area under the curve and introducing trend lines in an easily deployed case-finding search engine, frontline treaters are better equipped to pick up patients.
From here, the other panelists inject a series of thought-provoking questions, starting with Jörn’s focus on the patient response to this new pathway. Thus far, Tim is pleased to have received positive feedback and expects to conduct a comparative analysis as outreach expands. Jörn next prompts a thorough look into the computational components of this project. Tim explains a key to the system lies in “prepping the data” so that queries can generate cohorts of interest in mere seconds. This is an evolving effort that he works on closely with developers to craft bespoke technological solutions. Louise asks about what barriers, financial or otherwise, stand in the way of outreach efforts. Tim states that specifically financial barriers are being combatted with economic analysis to demonstrate the massive potential savings NHS can experience by adopting these preventative measures. Discussion segues back to computational power and the integration of assessing for the wider metabolic spectrum. Roger suggests that such a technology can offer an effective optical validity test before he shifts thoughts toward integration with other pathways.
As the session continues, Tim fields numerous prompts which delve into patient engagement, elements of data privacy, physician responses, the future of this project and much more. This is yet another eye-catching profile of an innovative technology in the Fatty Liver space contending to solve an immensely relevant challenge. Surf on for the full feature, and if you want to voice your own questions, be sure to write us
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As the podcast hosts insights from our very own audience this week, we are extending three additional conversations from recent reviews of a particularly exciting NASH-TAG 2023. This session features dialogue from a one-on-one interview with Donna Cryer, hosted by Roger Green.
The episode begins with Roger mentioning what he found to be one of the most striking statistics from the meeting: an IQVIA study captured only 200,000 total ICD-10 codes for NASH in a total US population that should have yielded 16 million such codes. To Donna, this underscores a significant need: we have to find physicians that want to treat patients. As she puts it, “it would do more harm than good” to send patients to doctors’ offices before doctors are activated to screen and treat. Roger identifies a dilemma: if patients aren’t visiting doctors, doctors will not feel motivated to learn. However, if patients are seen by unmotivated doctors, a negative information loop emerges. Donna notes lessons from the hepatitis care cascade and that at the outset, there is the need to screen an “enriched population” with higher probability of NASH. Roger suggests this is easier in the US, where electronic health records are standard. In much of the rest of the world, ALT tests are not part of a standard blood panel and too many records are on paper. Donna then emphasizes the need to dramatically increase advocacy and energy among medical stakeholders. She also points to what drug and diagnostic companies can do to energize physician practices to identify the patients needing treatment after a drug is approved. Finally, Roger asks Donna to rate her level of enthusiasm emerging from NASH-TAG. He offers a scale ranging from 1 to 6, where 1 represents “thoroughly depressed” and 6 represents “over the moon.” Her response addresses organization around regulatory science in a way that makes what is undeniable inevitable. Surf on to hear her gauge.
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This week, Surfing NASH has focused on community engagement and incorporating insights and perspectives from the listeners. If you enjoy our content, we kindly ask that you submit a review wherever you download our episodes. We also encourage our audience to write us questions and look forward to integrating your on-ground experiences and ideas in the weekly discourse. Most important of all, we whole-heartedly thank you for your continued support as we set out to put a major dent in Fatty Liver disease in 2023 and beyond.
Stay safe and surf on!
Stay Safe and Surf On!
As the podcast hosts insights from our very own audience this week, we are extending three additional conversations from recent reviews of a particularly exciting NASH-TAG 2023. This session highlights perspectives from patient advocates Tony Villiotti and Michael Betel as they join Louise Campbell and Roger Green for coverage of the first day at the conference.
The discussion begins with an idea from Tony and Michael that the cascading momentum the field is experiencing picked up steam at AASLD in November and carried on through the MOSAIC meeting in December. For advocates, the enthusiasm is largely centered on the likely approval of drugs in the near future and the sense of urgency this places, as Tony puts it, on expanding efforts to “get the message out.” Michael notes the importance of educating primary care physicians that there is something besides diet and exercise to support treatment. Louise adds that the alignment of specialties around screening is also critical to advancing Fatty Liver care. In response to a question from Michael, she makes explicit her belief that multidisciplinary alignment and statements will increase enthusiasm further. From there, Mike goes on to ask how the fact that diabetes and obesity patients might be on GLP-1s or dual agonists before being tested for liver disease might affect perceptions of the frequency of liver disease and/or the value of therapy. The remaining conversation focuses on the issue of how long patients must be on a medication. Louise likens it in her mind to autoimmune diseases, which will have flairs requiring medication. As the session winds down, Louise is discussing the breadth and depth of education she would like to see in the various medical stakeholder communities.
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This week, Surfing NASH has focused on community engagement and incorporating insights and perspectives from the listeners. If you enjoy our content, we kindly ask that you submit a review wherever you download our episodes. We also encourage our audience to write us questions and look forward to integrating your on-ground experiences and ideas in the weekly discourse. Most important of all, we whole-heartedly thank you for your continued support as we set out to put a major dent in Fatty Liver disease in 2023 and beyond.
Stay safe and surf on!
Stay Safe and Surf On!
As the podcast hosts insights from our very own audience this week, we are extending three additional conversations from recent reviews of a particularly exciting NASH-TAG 2023. This session features highlights from the wrap-up episode chat with Amy Articolo and Naim Alkhouri joining Jörn Schattenberg and Roger Green.
The leading question asks the panelists to rate their levels of enthusiasm emerging from the conference in Deer Valley. The scale ranges from 1 to 6, where 1 represents “thoroughly depressed” and 6 represents “over the moon.” A similar question at the conclusion of NASH-TAG 2022 elicited 4s and 5s… This time the answers ranged from Roger’s relatively conservative “6” to 6.5 or 7 from the rest. The optimism primarily was a result of the idea that two Phase 3 drug trials appear to have hit FDA’s efficacy and safety standards, with resmetirom meeting the EMA’s more challenging “regress fibrosis while lowering NAS score” standard. Jörn describes the implications of this as having proven that “it’s doable and druggable.” Roger adds, and Amy agrees, that the efficacy levels the two drugs hit appear to leave significant room for new drugs and combination therapies to improve efficacy. From there, the group goes on to discuss the implications of what we are learning about the impact bariatric surgery can have on NASH. This leads Naim to make a cogent comment which Jörn describes as “hitting it out of the park.” Listen to the full segment to hear this powerful viewpoint.
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This week, Surfing NASH has focused on community engagement and incorporating insights and perspectives from the listeners. If you enjoy our content, we kindly ask that you submit a review wherever you download our episodes. We also encourage our audience to write us questions and look forward to integrating your on-ground experiences and ideas in the weekly discourse. Most important of all, we whole-heartedly thank you for your continued support as we set out to put a major dent in Fatty Liver disease in 2023 and beyond.
Stay safe and surf on!
Stay Safe and Surf On!
In a thematic debut, Jörn Schattenberg and Roger Green host interviews with three listeners from the Surfing NASH community to discuss four prominent questions around:
- the “straightjacket” of biopsy
- how we think about “tests” when not classed as "NITs" as compared to biopsy
- how do we all become better centered on patient needs
- the idea of combination therapy
In this final installment, Clinical Development lead at Sonic Incytes, Caitlin Schneider, joins Roger to discuss NASH-TAG 2023 and the future of Fatty Liver. After discovering that Caitlin and Roger share one unusual detail in their pasts, they dive into a discussion of the conference. Sonic Incytes developed and markets Velacur™️, an in-office imaging solution. Not surprisingly, much of Caitlin’s focus revolves around imaging diagnostics and their benefits against biopsy and larger imaging technologies like MRE and MRI-PDFF.
Each guest in these fully-featured interviews shares on-ground experiences which collectively cast invaluable light on how the information featured in Surfing the NASH Tsunami is digested and applied in everyday life. As the podcast enters its fourth season, and embarks on affiliated journeys like the Rising Tide series, we hope to grow our community engagement. If you enjoy our content, we kindly ask that you submit a review wherever you download our episodes. We also encourage our audience to write us questions and look forward to integrating your on-ground experiences and perspectives in the weekly discourse. Most important of all, we whole-heartedly thank you for your continued support as we set out to put a major dent in Fatty Liver disease in 2023 and beyond.
Stay safe and surf on!
Stay Safe and Surf On!
In a thematic debut, Jörn Schattenberg and Roger Green host interviews with three listeners from the Surfing NASH community to discuss four prominent questions around:
- the “straightjacket” of biopsy
- how we think about “tests” when not classed as "NITs" as compared to biopsy
- how do we all become better centered on patient needs
- the idea of combination therapy
In this second installment, Jerry Mabary joins Roger to discuss NASH-TAG 2023 and the future of Fatty Liver. Jerry previously appeared on the podcast when he worked at Echosens and led their side of the LIVErHEALTHY launch. Now he has joined Chronwell, a LIVErHEALTHY partner and GE practice management support firm. As befits his background, Jerry’s conversation reflects heavily on non-invasive testing as well as the role digital apps will play in patient treatment. He weaves all this into an integrated vision of Fatty Liver care that incorporates the issues with the role of biopsy present and future. Finally, he notes ideas around the impact combination therapy will have on treatment over time.
Each guest in these fully-featured interviews shares on-ground experiences which collectively cast invaluable light on how the information featured in Surfing the NASH Tsunami is digested and applied in everyday life. As the podcast enters its fourth season, and embarks on affiliated journeys like the Rising Tide series, we hope to grow our community engagement. If you enjoy our content, we kindly ask that you submit a review wherever you download our episodes. We also encourage our audience to write us questions and look forward to integrating your on-ground experiences and perspectives in the weekly discourse. Most important of all, we whole-heartedly thank you for your continued support as we set out to put a major dent in Fatty Liver disease in 2023 and beyond.
Stay safe and surf on!
Stay Safe and Surf On!
In a thematic debut, Jörn Schattenberg and Roger Green host interviews with three listeners from the Surfing NASH community to discuss takeaways from NASH-TAG 2023 and the future of Fatty Liver. The four prominent questions of each session focus around:
- the “straightjacket” of biopsy
- how we think about “tests” when not classed as "NITs" as compared to biopsy
- how do we all become better centered on patient needs
- the idea of combination therapy
In this first installment, the co-hosts are joined by Pamela Danagher, Senior Vice President for Regulatory Affairs at Terns Pharmaceuticals. This conversation explores the ways that biopsy has, as Pamela puts it, constrained and restrained drug development. Not surprisingly, she also offers strong viewpoints and tremendous insights about uses of testing and combination therapy - two issues pivotal to Terns. Finally, Pamela comments briefly on what Donna Cryer described in a recent episode as “regulatory science” and how the entire community can communicate in ways that support approval of resmetirom and OCA.
Each guest in these fully-featured interviews shares on-ground experiences which collectively cast invaluable light on how the information featured in Surfing the NASH Tsunami is digested and applied in everyday life. As the podcast enters its fourth season, and embarks on affiliated journeys like the Rising Tide series, we hope to grow our community engagement. If you enjoy our content, we kindly ask that you submit a review wherever you download our episodes. We also encourage our audience to write us questions and look forward to integrating your on-ground experiences and perspectives in the weekly discourse. Most important of all, we whole-heartedly thank you for your continued support as we set out to put a major dent in Fatty Liver disease in 2023 and beyond.
Stay safe and surf on!
Stay Safe and Surf On!
In a thematic debut, this episode comprises three interviews held with our very own listeners from the Surfing NASH community to discuss their takeaways from NASH-TAG 2023 and the future of Fatty Liver.
Respectively, Pamela Danagher (Terns Pharmaceuticals), Jerry Mabary (Chronwell) and Caitlin Schneider (Sonic Incytes) join Jörn Schattenberg and Roger Green to explore four prominent questions around:
- the “straightjacket” of biopsy
- how we think about “tests” when not classed as "NITs" as compared to biopsy
- how do we all become better centered on patient needs
- the idea of combination therapy
Each guest shares insights which collectively cast invaluable light on how the information featured in Surfing the NASH Tsunami is digested and applied in everyday life.
As the podcast enters its fourth season, and embarks on affiliated journeys like the Rising Tide series, we hope to grow our community engagement. If you enjoy our content, we kindly ask that you submit a review wherever you download our episodes. We also encourage our audience to write us questions and look forward to integrating your on-ground experiences and perspectives in the weekly discourse. Most important of all, we whole-heartedly thank you for your continued support as we set out to put a major dent in Fatty Liver disease in 2023 and beyond.
Stay safe and surf on!
Stay Safe and Surf On!
In an exclusive interview, Co-Founder and Chief Scientific Officer of HistoIndex, Dr. Dean Tai, joins Fatty Liver Researcher Prof. Dr. Jörn Schattenberg on Surfing the NASH Tsunami podcast with host, Roger Green. The trio discuss pertinent questions stemming from data derived from Phase 2 trial results of aldafermin and resmetirom whereby liver volume reduction was achieved in a considerably abbreviated period. HistoIndex was able to subsequently investigate fibrosis reduction in these studies by conducting AI-assisted histologic assessment to gather a deeper understanding of fibrosis dynamics on a continuous scale.
Jörn introduces the corresponding poster held at NASH-TAG 2023, which reviews the application and compelling results of the qFibrosis® and qSteatosis® products. Dean then elucidates how AI-assisted zonal mapping of the liver delivers a targeted and statistically-improved assessment of fibrosis reduction. Interestingly, two distinctly different fibrosis regression patterns emerged between the aldafermin and resmetirom cohorts. The implication: highly-precise assessment of liver slides is sparking a spate of new questions surrounding therapeutic possibilities. Jörn offers two cogent observations. First, these technologies can drastically improve understanding of how much change in fibrosis really occurs. He points out that while many different MOAs are trialed in comparable populations, it may be that not all drugs are affecting fibrosis regression by the same mechanism. With the technology implemented by HistoIndex, researchers can now begin to assess the nuances of how and where these drugs act.
A different, but critically important idea emerges: patients deserve to have the fullest extent of utility extrapolated from their donated tissue. There is also noted to be a plethora of existing data containing what Dean describes as “a gold mine” for retrospective analysis. The group continues on to explore and compare the myriad of potential future applications of these tools. It becomes clear that advancements in AI-based digital pathology are paving a path for an entirely new, imaginative line of thinking for the Fatty Liver field. Listen to the full feature for more on this illuminating topic.
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NASH-TAG 2023 proved to be a watershed moment for Fatty Liver disease as exciting drug development readouts, powerful academic work on non-invasive tests and the willingness to dive into the toughest questions aligned in Deer Valley, Utah. In this weekend’s conversation series, Surfing NASH reviews its diverse coverage of the conference by showcasing key excerpts across six recordings with various KOLs, patient advocates and stakeholders.
This conversation consists exclusively of an exchange between Donna Cryer and Roger Green. The session begins by Donna noting that while the data is cause for enthusiasm, she is concerned that this alone does not guarantee an inevitable approval. In addition to good data, she suggests, is the need for good regulatory science. As she points out, Intercept hit its endpoints in 2020, yet no approval was gained at the time. “Good regulatory science” is, in her words, conclusive, granular and contains a simplified message. Roger asks for an example of what might not constitute good regulatory science. This leads Donna to recall that the fireside chat, although titled regulatory, focused more on clinical trial designs than how to prepare for advisory committees, health technology assessments and Phase 4 trials. She notes that during this discussion, a good question surfaced regarding how equipoise will change once drugs are approved. The implication: what FDA is currently seeking in Phase 4 becomes unrealistic once drugs reach the market. At this point, Roger returns to Scott Friedman’s comment about the “straitjacket of biopsy” and how that impacts thoughts around trial design and “proof.” Donna adds that real-world evidence is the up-to-date approach these days, and it will be available once we have more experience with the medicines.
As the session winds down, Roger goes back to the adiponectin analyses predicting non-response as being his favorite part of the meeting and explains why. Donna shares that one of her favorite moments came when Claude Sirlin, a radiologist, asked how they can become more involved here. Roger responds that radiology may succeed biopsy as a “hard standard” of efficacy. In the final moments, Donna discusses some of the presented data and questions that embodied a public health perspective.
Stay Safe and Surf On!
NASH-TAG 2023 proved to be a watershed moment for Fatty Liver disease as exciting drug development readouts, powerful academic work on non-invasive tests and the willingness to dive into the toughest questions aligned in Deer Valley, Utah. In this weekend’s conversation series, Surfing NASH reviews its diverse coverage of the conference by showcasing key excerpts across six recordings with various KOLs, patient advocates and stakeholders.
This conversation with Naim Alkhouri, Amy Articolo and Jörn Schattenberg begins with Naim illustrating some of the high points of the meeting. First, he recaps the resmetirom data. He then highlights that Intercept’s study of patient response to obeticholic acid (OCA) revealed improvements among the F3 population. He concludes that in the wake of these aforementioned results, there remains plenty of opportunity to improve and other biotechs “are still in the game” with the energy to back them. Jörn notes the high level of engagement from academia in supporting development through the consortia, NIMBLE and LITMUS. Amy credits the collaborative spirit of the meeting and the milestones achieved in improving the field’s understanding of how best to utilize NITs to provide insight and serve patient needs.
Roger Green steers conversation toward the challenges of payers and gaps in therapeutic efficacy for certain populations. He connects these ideas to slides presented by Naim on AI-driven zonal analysis developed by HistoIndex. The assessment provides a geographic vantage point that offers perspective on how to combine agent benefits and trial emerging opportunities. Amy agrees that some of the complex analytics will help pharma build its case for patients. Naim questions what we call “futility” – if patients stay the same, are they futile? He suggests that AI can help us determine whether people who do not reduce fibrosis are actually benefiting from therapy. Roger notes that Naim outlined three categories: patients whose fibrosis regressed, others who progressed and a third group somewhere in the middle yet to be defined. Naim agrees and underscores that with the non-invasive tests available, we can learn far more than what’s known today. Amy responds with questions around how tests will be used practically, noting that stacked tests are pivotal to the story. As the conversation ends, Jörn notes biopsy is only one way to generate a conditional endpoint for drug approvals.
Stay Safe and Surf On!
NASH-TAG 2023 proved to be a watershed moment for Fatty Liver disease as exciting drug development readouts, powerful academic work on non-invasive tests and the willingness to dive into the toughest questions aligned in Deer Valley, Utah. In this weekend’s conversation series, Surfing NASH reviews its diverse coverage of the conference by showcasing key excerpts across six recordings with various KOLs, patient advocates and stakeholders.
This conversation includes analysis by Scott Friedman, Rachel Zayas, Jörn Schattenberg, Louise Campbell and Roger Green. Roger leads by asking the group to detail the “sit up and take notice” moment of the meeting. Scott immediately describes the “800-lb gorilla in the room,” the resmetirom data, which casts a positive light around everything within the meeting at large. He goes on to discuss other key points, namely, compelling results for other drugs in earlier stage trials and NITs. Rachel agrees with Scott, stating that “the narrative has changed.” She also mentions Mary Rinella’s nomenclature talk and the discussion of combination therapies. Jörn praises the high energy level and well-rounded nature of the talks. Louise points to previously unpublished efruxifermin data from the HARMONY trial that suggested to her we can place drugs in primary care practices if we also ensure they have appropriate tools and tests to monitor patients.
Scott underscores perhaps the most staggering number in the meeting: only 3% of patients treated for NASH are treated by a hepatologist. Jörn concurs with this observation, adding that this casts light on the importance of using the NITs at hand to identify patients. Scott then referred back to Will Alazawi’s presentation on pathways and a brief presentation from Siemens evaluating four different test strategies in terms of lowest cost and highest prediction. Roger comments that the wealth of NIT data is actually starting to point to simple strategies for using them in clinical trials and treating patients. The uses may vary, but the paths seem clear. For Roger, Fagan’s nomogram, which Mike Charlton presented, was the moment at which the paths became clear. He next asks Scott to describe what he considers most pivotal here. Scott goes on to discuss the need to identify non-responders better and figure out how to best manage them. Jörn agrees in the profundity of this analysis and, in that context, calls into question whether our definition of “response” might change from fibrosis regression to something more broadly metabolic. As the talk winds down, Louise notes that we have seen some promising data about combination therapies. Lastly, Scott notes that we have far more scientific ways to approach combination therapy than simply seeing what drugs a company has in its portfolio.
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NASH-TAG 2023 proved to be a watershed moment for Fatty Liver disease as exciting drug development readouts, powerful academic work on non-invasive tests and the willingness to dive into the toughest questions aligned in Deer Valley, Utah. In this weekend’s conversation series, Surfing NASH reviews its diverse coverage of the conference by showcasing key excerpts across six recordings with various KOLs, patient advocates and stakeholders.
This conversation featuring Stephen Harrison, Mazen Noureddin and Jörn Schattenberg begins with Mazen describing how exciting and informative the new sessions on non-invasive tests were. Specifically, he details his own surprise at how much LITMUS and NIMBLE were able to share. Jörn’s main point: we will find more NITs, but do not need them to be able to push treatment far forward today. Roger Green suggests that correct classification metrics (based on the percentage of patients classified correctly) might be more important in practical treatment than other tests which have better positive or negative predictive values but have large “indeterminate zones” of patients the test does not predict for at all. Stephen compliments the NIT discussion and commends Mazen’s observation that NASH is not the only disease area working its way through predictive non-invasive tests. Mazen shifts discussion onto the next session, where Vlad Ratziu, Rohit Loomba and Stephen Harrison investigate important areas in clinical trial design. Vlad discussed combination therapies, Rohit discussed gene SNPs and Stephen discussed cirrhosis.
Stephen refocuses on the idea that by providing continuous scoring, NITs appear to provide better guidance on whether drugs are “working” or not. Mazen agrees, pointing out how high the bar is to label a patient treated with drug a success. As the talk winds down, Jörn notes that Intercept and Madrigal are providing data we can dive into for years. Lastly, Stephen describes the high value that AI-based digital pathology will provide in sorting out how many patients are improving using continuous measures.
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NASH-TAG 2023 proved to be a watershed moment for Fatty Liver disease as exciting drug development readouts, powerful academic work on non-invasive tests and the willingness to dive into the toughest questions aligned in Deer Valley, Utah. In this weekend’s conversation series, Surfing NASH reviews its diverse coverage of the conference by showcasing key excerpts across six recordings with various KOLs, patient advocates and stakeholders.
This conversation features our patient advocate discussion with NASH kNOWledge founder, Tony Villiotti, and Fatty Liver Alliance Founder and CEO, Michael Betel. Tony and Michael begin by describing the high levels of enthusiasm that began at AASLD and carried through to NASH-TAG as it became clear that there are drug trials appearing to meet all criteria for approval. Louise Campbell extends this sentiment further, commenting that new medications combined with greater awareness of the breadth of integrated metabolic disease is leading to a surge in collaboration with other specialists. Specifically, she refers to the involvement of cardiology and endocrinology specialists as a “game changer.”
Mike shifts focus to the idea that patients with diabetes and/or obesity might be taking GLP-1s or dual glucagon agents for those diseases. He points out that should new NASH drugs be approved, this might lead to de facto combination therapy. Louise suggests reasons why this might be a double-edged sword. The remainder of the episode focuses on things we do not know about the drugs – how they interact, how long they will work and what downsides may be. Louise offers a final thought which emphasizes the importance of providing professional and patient education and training to make sure the new medicines are used properly.
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For our look back at NASH-TAG 2023, Jörn Schattenberg and Roger Green are joined by Amy Articolo and Naim Alkhouri for a discussion which dives into the therapeutic efficacy of recently announced data on resmetirom, NITs, bariatric surgery and more. Adjoining this session is a bonus interview with Donna Cryer on her impressions and key takeaways which largely look into the movement of regulatory science. In combination, this two-part episode encompasses contrasting and thought-provoking perspectives on addressing the opportunities and challenges in moving the Fatty Liver field forward.
Naim opens the first conversation by noting the positivity emitted, echoing Scott Friedman’s position that momentum from Madrigal’s emerging data on resmetirom animated the wider program. In addition, he highlights that granularity around Intercept’s study of patient response to obeticholic acid (OCA) revealed improvements among the F3 population. For Naim, OCA is a drug he has envisioned to be applied toward advanced disease and serves undermet needs of F3 patients. He concludes that in the wake of these aforementioned results, there remains plenty of opportunity to improve and other biotechs “are still in the game” with the energy to back them.
At this point, Jörn underscores the strong presence of academia and involvement of various consortia as further evidence of progress. Amy joins to comment on the vibrant and dynamic discussions around NITs and how to enrich trials. She suggests that the dialogue has reflected the advancements of the field and how work can be enhanced with collective contribution. This leads to thoughts on pharmacodynamic change and demonstrating value to payers. Roger distills a main idea: if only 24% of patients show a one-level regression of fibrosis in a given period of time, there is much to learn about the other 76%. Conversation continues around narrowing the indeterminate zone and improving biomarker concordance in NITs. After exploring considerations in moving beyond biopsy, the group investigates the role of bariatric surgery. While recognizing the validity of bariatric surgery as a treatment option, Naim points to a brighter future of preventative hepatology whereby action precedes BMI levels of 50 and higher. At the end of the session, Roger asks each panelist for one unexpected thing that might happen in the next year.
In the following interview, Donna opens with a powerful statement: hope is not a strategy, and optimism is not inevitability. Specifically, she is determined to match the trajectory of regulatory science to that of the momentous energies emerging from clinical science. In doing so, relationships and open lines of communication are key for meeting agreed endpoints. Next, the two talk about addressing the indeterminate zone in a different context and opportunities for harnessing real-world evidence. As this conversation moves forward, it becomes clear that Donna is committed to connecting patients to care today, and not only after a drug approval. In closing, she fields the same question as the preceding panelists, but offers a very different answer. Surf on to find out.
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In Part 2 of our real time coverage of the highly anticipated NASH-TAG 2023 conference, friends of the podcast Scott Friedman and Rachel Zayas join Louise Campbell, Jörn Schattenberg and Roger Green to review key takeaways from Friday and Saturday in Deer Valley. Following this session, Jörn, Louise and Roger review high points from the Saturday night “Potpourri” and “Regulatory Fireside Chat” sessions. The final feature of this episode is an enthralling and exclusive interview with HistoIndex Co-Founder and Chief Scientific Officer, Dean Tai, who shares captivating data from an AI-assisted histologic assessment of Phase 2 trials on aldafermin and resmetirom.
Scott opens the leading session with a concise summary of his highlights distilled from an event burgeoning with impressive moments. His main suggestion is that the positive momentum of the recent Madrigal announcement energized the wider program. Rachel echoes the idea that “the narrative has changed” as the field enters a promising New Year. Next, Louise points to her interest in the presentation of previously unreleased Phase 2 results from the HARMONY Trial on efruxifermin. And finally, Roger speaks to the evolving roles that NITs play in clinical trial and primary care settings. As analysis advances, Scott nails down an important question: what are the factors that distinguish the responders from the non-responders in the resmetirom trial? This leads the group down a compelling line of interrogation. The question also proves pertinent later in the episode as Dean teases tools to uncover the nuances of how and where these drugs act in the liver and beyond. Other topics explored in the opening session include insights on combination therapy, covert alcohol use, bariatric surgery, nomenclature, NITs, genetics and more.
In the second conversation, Jörn, Louise and Roger dive deeper into Saturday’s session. A major theme: the increasing focus on the role of bariatric surgery in liver disease. Jörn also underscores discussion around moving the field forward with an NIT that predicts outcome as an acceptable surrogate for conditional drug approval. Roger comments that addressing how drugs get used - not how they get approved - shifts focus from the needs of regulators to those of the payers.
Lastly, Dean joins Jörn and Roger to investigate fibrosis dynamics on a continuous scale using AI-based analysis and quantification of NASH features for treatment efficacy. The main idea: highly-precise assessment of liver slides has arrived, sparking a spate of new questions surrounding therapeutic possibilities. It becomes clear that advancements in AI digital pathology are paving a path for an entirely new, imaginative line of thinking for the Fatty Liver field. Surf on to the full feature for more on this illuminating topic.
This episode of Surfing the NASH Tsunami, including the accompanying discussion on zonal and liver-volume corrected analysis of fibrosis and steatosis, is sponsored by HistoIndex, the world’s leading specialist in stain-free imaging for NASH clinical trials. HistoIndex is transforming diagnostic standards and drug development for NASH with its second harmonic generation based AI digital pathology solution.
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In a riveting debut of Season 4 on Surfing the NASH Tsunami, the podcast offers real time coverage of the highly anticipated NASH-TAG 2023. This episode includes two recordings. In the first conversation, NASH-TAG 2023 co-course director Stephen Harrison, scientific advisory board committee member Jörn Schattenberg and fellow Key Opinion Leader Mazen Noureddin join Roger Green to review presentations and themes from the Friday afternoon session. This conversation centers largely around Friday afternoon’s presentation on NITs. The group focuses on the expansion in NIT knowledge in terms of the number of NITs available, the breadth of knowledge they cover and the ways NITs can be used to manage patients wisely today. The conversation also focuses on the features that make NASH-TAG such a unique meeting.
In the second conversation, Fatty Liver Alliance Founder Michael Betel and NASH kNOWledge Founder Tony Villiotti join Roger and Louise Campbell. This discussion highlights how the momentum of recent pivotal trials in NASH drug development is changing patient advocacy today. The main insight: as more information becomes available and as we see successful Phase 3 drug trials, the number of stakeholders needing information increases and what each group needs to know varies. All this portends an exciting future for patients and their caregivers.
To discover the energy for yourself, surf on to the episode and stay tuned with our continued coverage.
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In the Season 3 NAFLD Year-in-Review conversations series, Surfers Jörn Schattenberg, Louise Campbell and Roger Green embark on a string of interviews with a handful of Key Opinion Leaders who made headlines and advances in Fatty Liver disease in 2022. In this final segment, Ian Rowe joins Jörn and Roger to share his takeaways.
Ian begins this conversation by discussing his impressions on Madrigal’s announcement of positive topline results from the Phase 3 MAESTRO-NASH trial of resmetirom. He describes the event as a milestone in the development of NASH therapies that illuminates the need to prepare for how to most meaningfully make future treatments accessible to patients. This segues into regulatory frameworks and process of approval through NICE in the UK. From here, Roger steers conversation to consider efforts in the UK to expand Fatty Liver screening into primary care. Ian goes on to discuss at depth the pivotal role NITs will come to play in patient management.
Looking toward the future and excitement around drugs coming to market, Ian describes two tangible ways he envisions a shift in his practice. First, he highlights the importance of driving disease awareness and education around prognosis. Second, he hopes energies and insights will increase interest and focus into the alcohol-related liver disease which dominates his inpatient practice. The group continues on to compare and contrast ideas around a shared pathway, stigmas and other nuances around alcoholic versus nonalcoholic liver diseases. As the conversation wraps up, Ian shares what he hopes for and expects in 2023.
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In the Season 3 NAFLD Year-in-Review conversations series, Surfers Jörn Schattenberg, Louise Campbell and Roger Green embark on a string of interviews with a handful of Key Opinion Leaders who made headlines and advances in Fatty Liver disease in 2022. In this exclusive segment, podcast co-founder and former co-host, Stephen Harrison, joins Louise and Roger to discuss the year-in-review as recorded before Madrigal’s breaking announcement of the Phase 3 MAESTRO-NASH results last week.
From the outset, Stephen admits there were “a lot of pleasant surprises” this year, alluding to the multiple positive Phase 2 trial results among other recent press releases. He anticipates several exciting modes of action becoming available in the imminent future. The interview goes on to look at advancements made in methodology of interpreting liver biopsies, understanding the limitations of biopsy and degrees of mitigation in response to those shortcomings. Stephen also offers in-depth investigation into the uptake of NITs as conditional clinical trial endpoints, something he sees as a process whose momentum keeps growing and strengthening.
Throughout this session, Stephen provides speculation as to what the promising new year holds for the Fatty Liver field. In his words, 2022 revealed “the most incremental advances in the field of NASH in the past decade.” He adds that, like this year, 2023 is primed to be pivotal. Surf on for the full-length, insight-laden interview with a remarkable physician and Principal Investigator making tremendous contributions to the pursuit of putting a major dent in Fatty Liver.
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In the Season 3 NAFLD Year-in-Review conversations series, Surfers Jörn Schattenberg, Louise Campbell and Roger Green embark on a string of interviews with a handful of Key Opinion Leaders who made headlines and advances in Fatty Liver disease in 2022. In this exclusive segment, Naim Alkhouri joins Louise and Roger to discuss drugs, NITs, digital diagnostics and the importance of preventing pediatric and adolescent NAFLD.
Naim begins by highlighting the FDA approval of the ELF test, which has assisted him in the risk stratification of patients who fall in the indeterminant zone. He then underscores an impressive spate of positive moments from the year, touching on AASLD presentations and guidance documents, and clinical trial results and the implications for NASH therapeutics. After expanding on developments in digital diagnostics, Naim points to how this improves screening for the diabetic population and ultimately can further prevent disease progression. Louise prompts comments around the availability and efficacy of FIB-4. Naim suggests that outside of special patient populations at elevated risk for liver disease, FIB-4 poses limitations to be addressed. The conversation continues on the subjects of lifestyle interventions and the alarming prevalence of NAFLD in younger populations. Naim points out that with 15% of children and 25% of adolescents and young adults having NAFLD, treating fatty liver is a preventative measure against diabetes. He states he would like to design and execute a clinical trial that further investigates this relationship.
The group next explores the idea of preventative hepatology and the bigger picture role of primary care in combating NAFLD. As the conversation winds down, they discuss elements of emerging drug developments and closing thoughts on the momentous year. Surf on for more takeaways from what is an infectiously optimistic and compelling interview. As he usually does, Naim covers a tremendous amount of intellectual territory clearly and concisely in not that much time.
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The latter half of December marks the Surfing the NASH Tsunami annual NAFLD Year-in-Review. In Part 3 of this Season 3 finale, Surfers Jörn Schattenberg, Louise Campbell and Roger Green interview Naim Alkhouri, Stephen Harrison and Ian Rowe to discuss putting a dent in Fatty Liver disease in 2022 and beyond. This final episode of the year features compiled excerpts from our respective guest interviews. Each interview in its entirety will debut as independent segments released over the weekend.
Surf on to hear the diverse and powerful perspectives provided by a handful of the field’s Key Opinion Leaders who made headlines and advances in Fatty Liver disease in 2022.
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In the Season 3 NAFLD Year-in-Review conversations series, Surfers Jörn Schattenberg, Louise Campbell and Roger Green embark on a string of interviews with a handful of Key Opinion Leaders who made headlines and advances in Fatty Liver disease in 2022. In this exclusive segment, Jeff Lazarus opens in full disclosure admitting that, overall, 2022 has been a tough year in health care as “everyone is overwhelmed” while we all try to emerge from the pandemic. Regarding the status of Fatty Disease, Jeff is more optimistic as this year witnessed movement outside of hepatology into the space of diabetes societies and primary care meetings. Such collaborative energy is needed “to understand the metabolic syndrome and not just silos.” Jeff goes on to cite a return to an in-person Wilton Park meeting as an example turning point for such synergies.
The conversation evolves to consider targets, goals, endpoints and some small distinctions between each in the framework of public health. Jeff notes that we will need what he describes as a “drugs-plus approach” to address Fatty Liver disease - similar to that vaccines were not the single defense in combating the COVID pandemic. While drug therapies may be the cornerstone for fatty liver disease, there remains the need for lifestyle interventions through diet and exercise. As Jeff indicates, this mission is larger than hepatology alone. While a wider net of stakeholders establish clinical care guidelines in the context of professional societies, there still lacks, in example, a technical strategy coming from an organization such as the W.H.O. Jeff believes establishing work around the Sustainable Development Goals is important in showing the connection between different targets and the liver. He extends this idea to connect socioeconomic variables to liver health outcomes.
The group also explores the idea that when drugs become available to market, treater interest picks up because there is encouragement from the fact that something that can be done. Jeff hopes this positive energy will also recruit more resources in the form of nutritionists and dieticians. He raises questions around imagining what new models of care look like, and how do we improve communications and teamwork. His response: the availability of drugs and the imminent availability of drugs will set fire to the changes that will need to follow. He adds comments on the importance of addressing the policy arena and ensuring policymakers and health authorities are aware of the potentially deadly, highly prevalent condition. They need to be aware that there are soon to be approved and available drugs, and that the majority of this population is undiagnosed. Jeff further reasons that Fatty Liver is in need of a more proactive approach that identifies and educates on the risks of disease progression before advanced fibrosis takes hold. As the conversation winds down, the group investigates the implications and process behind ongoing discussion on nomenclature.
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In the Season 3 NAFLD Year-in-Review conversations series, Surfers Jörn Schattenberg, Louise Campbell and Roger Green embark on a string of interviews with a handful of Key Opinion Leaders who made headlines and advances in Fatty Liver disease in 2022. In this exclusive segment, Ken Cusi expands on “the year it all came together.”
Ken opens by stating that 2022 has been a momentous year for fighting Fatty Liver as a result of decades of work from a myriad of groups and contributors. He specifically points to the critical efforts of developing guidelines in preparing the field for a drug approval - especially as Phase 3 trials suggest new NASH therapies are on a shorter-term horizon. The culmination of these guidelines and progression toward earlier screening primes 2023 to be yet another historic year. All of which underscores the importance of driving education and increasing awareness of liver health. It's suggested that 2022 has been the year in which the field expanded beyond the interest of hepatologists alone and adopted the attention and collaborative energy of a wider net of stakeholders, including endocrinologists and primary care professionals. From here Ken expands on a brief roadmap as to how we arrived at these points of convergence.
The conversation continues with comments on the versatility of the FIB-4 test. The group revisits a common topic on this podcast whereby different systems from around the world are compared and contrasted in terms of their capacities to utilize FIB-4 and other liver health data in an electronic medical record. Ken reiterates the importance of patient education going forward as he believes patients have an active role to play in the collective goal of putting a dent in Fatty Liver disease. As the conversation winds down, he addresses a number of other subjects including thoughts on nomenclature, different approaches to weight-loss therapies, and the role of policymakers in promoting liver health.
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In the Season 3 NAFLD Year-in-Review conversations series, Surfers Jörn Schattenberg, Louise Campbell and Roger Green embark on a string of interviews with a handful of Key Opinion Leaders who made headlines and advances in Fatty Liver disease in 2022. In this exclusive segment, Mazen Noureddin reflects on both personal and professional developments.
Mazen begins by describing a move from Los Angeles to Houston where he is focused on establishing the state-of-the-art Houston Research Institute. He next highlights contributing to the development of a highly specific MRI-based (MAST) score to identify patients with fibrotic NASH as a major achievement of the year. In another underscore, Mazen points to presenting an abstract at AASLD last month on top-line results from a phase 2a trial on the mitochondrial uncoupler, HU6. Jörn joins to prod into the latter presentation and ask whether mechanisms trialed in obesity and other metabolic diseases are trending toward being investigated within hepatology. Mazen suggests that while mitochondrial uncouplers have been explored for many years, recent innovation in NASH can be an expected path given the nature of being a multi-systemic disease. He goes on to describe determining nuances in the efficacy of weight-loss medications and their different mechanisms of action.
From here the conversation picks up on the increasing optimism around the use of NITs and Mazen’s involvement with the NAIL-NIT Consortium. Roger notes that earlier in the year, Mazen stood out as someone who aggressively pushed a closing window toward moving beyond the biopsy. Remarkably, Mazen’s optimism and confidence in the development and implementation of NITs still projects these faster advancements. As the session winds down, Mazen speaks to what he hopes to see in the coming year.
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The latter half of December marks the Surfing the NASH Tsunami annual NAFLD Year-in-Review. In Part 2 of this Season 3 finale, Surfers Jörn Schattenberg, Louise Campbell and Roger Green interview Mazen Noureddin, Ken Cusi and Jeff Lazarus to discuss putting a dent in Fatty Liver disease in 2022 and beyond. This episode features compiled excerpts from our respective guest interviews. Each interview in its entirety will debut as independent segments released throughout the week.
Surf on to hear the diverse and powerful perspectives provided by a handful of the field’s Key Opinion Leaders who made headlines and advances in Fatty Liver disease in 2022.
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In a monumental moment in the never-ending pursuit of putting a major dent in Fatty Liver disease, Madrigal Pharmaceuticals announced positive topline results from the pivotal Phase 3 MAESTRO-NASH clinical trial of resmetirom for the treatment of NASH and liver fibrosis. Madrigal’s leadership intends to file for resmetirom’s accelerated approval with the FDA in the first half of 2023. If approved, the drug may become the first NASH medication introduced to market, depending on the outcome and timing of Intercept Pharmaceuticals’ refiling of obeticholic acid.
To recognize this special occasion, Surfing the NASH Tsunami hosts its largest ever suite of panelists who react to the enthusiasm, synergy and implications surrounding the news. This final conversation starts with Roger Green following up on a couple of earlier comments. First, he notes the fact that in other diseases, a combination therapy can get approved before each element of monotherapy has been approved. Second, he notes that semaglutide’s Phase 2 result, with 72-week effects on steatosis and NAS activity score but not fibrosis regression, aligns with Scott Friedman’s earlier statement that not all fat lowering may mean the same thing in the liver. Jörn Schattenberg and Mazen Noureddin follow-up with other comments about NAS, fibrosis and lipotoxicity. This leads Jörn to note that there is already a second THR-beta in trial, from Viking Therapeutics, and asks what this trial might mean for Viking. Mazen cites Terns as another company with other drugs, including a THR-beta in the pipeline, and believes they will benefit as well. Scott asks what all this means for patients with cirrhosis. Rachel Zayas then discusses some of the development work her company is doing and how these results might affect her work and ability to raise resources. As the session winds down, Kris Kowdley describes one more way that the use of companion diagnostics against dose response and non-response will aid payers. For her final thoughts, Louise Campbell discusses how we might consider this a major anti-cancer advance given how the liver is implicated not only in HCC but also in non-hepatic cancers. Surf on to hear the diverse array of closing takeaways from the rest of the group.
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In a monumental moment in the never-ending pursuit of putting a major dent in Fatty Liver disease, Madrigal Pharmaceuticals announced positive topline results from the pivotal Phase 3 MAESTRO-NASH clinical trial of resmetirom for the treatment of NASH and liver fibrosis. Madrigal’s leadership intends to file for resmetirom’s accelerated approval with the FDA in the first half of 2023. If approved, the drug may become the first NASH medication introduced to market, depending on the outcome and timing of Intercept Pharmaceuticals’ refiling of obeticholic acid.
To recognize this special occasion, Surfing the NASH Tsunami hosts its largest ever suite of panelists who react to the enthusiasm, synergy and implications surrounding the news. This conversation starts with Jörn Schattenberg investigating the impact that the use of a broad set of NITs in this study will have on NIT adoption and use in clinical patient treatment. Mazen Noureddin comments on how the use of NITs in clinical trials can reduce recruitment time and costs associated with the trials. Scott Friedman points out that as we strive to learn how to identify drug failures faster, FDA might require broad NIT use as part of that effort.
As the conversation continues, Rachel Zayas and Scott jump into more basic scientific issues. Rachel asks whether there is synergistic effect between LDL lowering and the primary endpoints and what that means for the disease. Scott asks what the results tell us on two fronts: first, what does it tell us about the ability of fat lowering to regress fibrosis if THR beta has no direct antifibrotic effect. Second, what about this drug converts fat lowering into fibrosis regression when other drugs that can lower fat and maintain lower fat levels do not demonstrate antifibrotic effects? After more comments about the science of the trial, Michael Betel asks how quickly focus will shift from monotherapy to combination therapy given how many patients did not succeed with resmetirom monotherapy. Mazen notes that other therapies were administered to patients in this trial. As the session ends, Louise Campbell asks questions about semaglutide design and Mazen discusses benefits and trial opportunities for this drug.
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In a monumental moment in the never-ending pursuit of putting a major dent in Fatty Liver disease, Madrigal Pharmaceuticals announced positive topline results from the pivotal Phase 3 MAESTRO-NASH clinical trial of resmetirom for the treatment of NASH and liver fibrosis. Madrigal’s leadership intends to file for resmetirom’s accelerated approval with the FDA in the first half of 2023. If approved, the drug may become the first NASH medication introduced to market, depending on the outcome and timing of Intercept Pharmaceuticals’ refiling of obeticholic acid.
To recognize this special occasion, Surfing the NASH Tsunami hosts its largest ever suite of panelists who react to the enthusiasm, synergy and implications surrounding the news. This conversation starts with Louise Campbell commenting on two specific benefits. First to mention is the fact that the multiple metabolic measurements "check a lot of boxes," as she puts it, in terms of liver disease. Second, she notes there is great benefit for patients now that caregivers can tell them “if diet and exercise does not work, there is something else we can do.” Mazen Noureddin agrees, but notes that for F3 patients, drug therapy should start on the first or second visit. He also discusses the value of Hispanic patients and ways to discuss efficacy. Jörn Schattenberg asks whether the relatively similar results at two dose levels build or defeat the case for two dose levels. Kris Kowdley states confidently that having two dose levels is a benefit that these results demonstrate.
Louise asks how we can drill down into the patients that did not succeed, and Scott Friedman raises issues around payer response and precision therapy. He notes that it may also redefine use of placebo in clinical trials. Michael Betel asks what role bariatric therapies – notably surgery – might play in liver therapy and how we evaluate it. Through the rest of this session, Kris, Mazen and Roger discuss ways that the scope of data in this study and the rest of the Madrigal program will enrich scientific knowledge for years to come.
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In a monumental moment in the never-ending pursuit of putting a major dent in Fatty Liver disease, Madrigal Pharmaceuticals announced positive topline results from the pivotal Phase 3 MAESTRO-NASH clinical trial of resmetirom for the treatment of NASH and liver fibrosis. Madrigal’s leadership intends to file for resmetirom’s accelerated approval with the FDA in the first half of 2023. If approved, the drug may become the first NASH medication introduced to market, depending on the outcome and timing of Intercept Pharmaceuticals’ refiling of obeticholic acid.
To recognize this special occasion, Surfing the NASH Tsunami hosts its largest ever suite of panelists who react to the enthusiasm, synergy and implications surrounding the news. This conversation is the first in a series which navigates the reactions of eight panelists, including Michael Betel, Scott Friedman, Kris Kowdley, Mazen Noureddin, Rachel Zayas and co-surfers Jörn Schattenberg, Louise Campbell and Roger Green. As each recalls their various reactions to the news, the group addresses several points. Mazen describes his relief that we now have a Phase 3 trial that achieves efficacy and safety goals. Scott follows up with his anticipation of increased enthusiasm and energy for the entire set of stakeholders. Michael, the patient advocate representative among the group, reacts with a question: are we ready? Comments from Kris and Jörn drive one interesting outlook: this is the second positive Phase 3 trial in terms of efficacy. Such results might clear the field for a simpler approval process. Additionally, Jörn notes an approval would be in consideration in the EU where EMA requires both NAS improvement and regression of fibrosis.
From the entrepreneur’s perspective, Rachel recalls her decision a couple of years ago to pivot her company from hepatocellular carcinoma to NASH as what she calls a “bet on science.” This statement aligns with Roger’s persistent belief that this study will open the doors for more investment. Jörn and Mazen discuss some of the specific elements of patient screening and population that demonstrate the power of this study. As the session winds down, Roger shares an interesting observation: while the researchers have begun by talking about patients, in an earlier, separate conversation Donna Cryer began by talking about investors.
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In a monumental moment in the never-ending pursuit of putting a major dent in Fatty Liver disease, Madrigal Pharmaceuticals announced positive topline results from the pivotal Phase 3 MAESTRO-NASH clinical trial of resmetirom for the treatment of NASH and liver fibrosis. Madrigal’s leadership intends to file for resmetirom’s accelerated approval with the FDA in the first half of 2023. If approved, the drug may become the first NASH medication introduced to market, depending on the outcome and timing of Intercept Pharmaceuticals’ refiling of obeticholic acid.
To recognize this special occasion, Surfing the NASH Tsunami hosts its largest ever suite of panelists who react to the enthusiasm, synergy and implications surrounding the news. This first conversation from the series incorporates highlights of our exclusive discussion with Donna Cryer, Founder and CEO of the Global Liver Institute. Donna focuses her initial comments around the MAESTRO-NASH data and the ways it benefits the overall field and demonstrates sustainability for NASH therapy as a whole. She extends her notes to consider the breadth of the Madrigal program and its implications for the full range of patients. Another consideration explores the program’s impact on practical use of NITs in demonstrating value in patient management and to the various stakeholders interested in building integrated systems. As Roger describes, this conversation is “pulling on all threads” of what these results and this energetic moment mean for sustainability in the field. This is a rich dialogue with many more notes and insights on how this story develops our understanding of where the liver fits in both the biological system and what efforts are required to integrate healthcare systems with timely, seamless adoption.
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NASH-TAG 2023 co-course director Stephen Harrison and scientific advisory board committee member Jörn Schattenberg join Louise Campbell and Roger Green to preview what is shaping to be a highly anticipated conference leading the field into a promising New Year. In light of Madrigal’s announcement of positive topline results from the MAESTRO-NASH trial of resmetirom, the first half of this conversation focuses on Stephen’s assessment of the emerging story. He then provides an overarching walk through of the format and schedule for the event held in Park City, Utah on January 5-7. The group notes there to be a full stack of “wow” presentations embedded in the program in addition to the developing takeaways from Madrigal’s announcement. Jörn looks forward to discourse on what he calls the “next generation of NITs” and Louise highlights an interest in updates on moving pathways forward. Surf on for the full preview and visit the NASH-TAG 2023 website to review this riveting agenda.
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Yesterday, in a monumental moment in the never-ending pursuit of putting a major dent in Fatty Liver disease, Madrigal Pharmaceuticals announced positive topline results from the pivotal Phase 3 MAESTRO-NASH clinical trial of resmetirom for the treatment of NASH and liver fibrosis. Madrigal’s leadership intends to file for resmetirom’s accelerated approval with the FDA in the first half of 2023. If approved, the drug may become the first NASH medication introduced to market, depending on the outcome and timing of Intercept Pharmaceuticals’ refiling of obeticholic acid.
To recognize this special occasion, Surfing the NASH Tsunami hosts its largest ever suite of panelists who react to the enthusiasm, synergy and implications surrounding the news. Alongside regular Surfers Jörn Schattenberg, Louise Campbell and Roger Green are friends of the podcast, Michael Betel, Donna Cryer, Scott Friedman, Kris Kowdley, Mazen Noureddin and Rachel Zayas. This is an unmissable, full house discussion which surveys what is primed to be a momentous breakthrough for the field. Read the Madrigal press release and surf on to hear what is to be a memorable episode.
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In another exciting installment of the Surfing NASH year-end interview series, Jörn Schattenberg, Louise Campbell and Roger Green are joined by Donna Cryer, founder, president and CEO of the Global Liver Institute (GLI). This conversation embodies the progressive and collaborative energy of GLI from the outset, beginning with Donna’s explanation that they now have NASH materials available in sixteen different languages. And while acknowledging the momentous nature of 2022, she points positively and determinedly toward what could be an even more remarkable 2023. The diversity of efforts extending across the GLI network have never been so far-reaching. This array of engagement is exactly why GLI is now making its preparations to capitalize on a flood of opportunities that may arrive with any drug approvals. Looking back at an eventful year, what stands out to Donna are things like being involved in co-authoring a paper for the National Committee for Quality Assurance. Quality measures are especially important as the field develops and implements guidelines and pathways so that patients have meaningful access to treatments.
The conversation continues on the track of what is required in terms of preparedness as Donna also describes de-risking the environment with GLI presence and readiness for investments in liver health to ensure sound, equitable pricing is placed on any approvals. There is the need to adequately characterize and profile patients’ different risk stratification and comorbidity profiles and match the right combination of treatments to them. This idea segues to the importance of screening and the challenge of identifying all those who need treatment that remain undiagnosed. From here, Jörn prompts Donna to discuss illuminating perspectives on quantifying quality of life considerations and how much focus should be allotted to these measures. She suggests both more expanded holistic benefit design and a more diversified workforce will positively contribute to the varying needs of patients at different stages of disease. Roger next leads discussion to consider the dynamism of investment energies that can play a pivotal role in education and driving action toward more preventative liver health solutions. Donna agrees this line of defense continues to develop and impart a positive influence on the space, be it through emerging technology, community-based resources or a combination of both.
There are many more takeaways to be gleaned from this exceptional interview which champions the patient perspective. Donna provides tremendous and directed optimism to this conversation, presaging another impactful year to come for GLI. Surf on to learn more.
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In this exclusive interview, Hannes Hagström joins Jörn Schattenberg, Louise Campbell and Roger Green to explore papers emerging from Scandinavia which offer fascinating insights to the field at large.
Hannes opens the conversation with his idea that 2022 was an encouraging year for research, specifically in that the mechanisms of drugs in development “feel more realistic.” When asked what he means by realistic, Hannes explains his interpretation of NAFLD to be a public health problem by which the metabolic system is overloaded with nutrients. He suggests a general pathway would aim to reduce this burden, citing examples like GLP-1s and possibilities surrounding an imminent announcement on resmetirom. From here Hannes describes developing a population-based cohort of liver disease patients using relatively accurate registers in Sweden. He highlights that this system enables studies to navigate issues around selection bias and capture the whole of a population with any diagnosed liver disease dating back to the sixties - roughly 350,000 unique patients in Sweden. The data available in this cohort can be linked back to the general population and used to examine several important research considerations. Long-term outcomes of chronic liver diseases, risk factors for disease progression, impact of dispensed drugs, disease panorama and time trends are among examples.
Segueing to several studies utilizing this cohort, Hannes first introduces a paper which examines cardiovascular disease (CVD) risk and life expectancy in patients with NAFLD compared with the general population. While NAFLD was associated with a higher risk of nonfatal CVD, it notably did not affect post-CVD mortality risk. Another conclusion: patients diagnosed with NAFLD have a lower life expectancy than the general population. Strikingly, this loss in life expectancy was accentuated depending on the age of patient at time of diagnosis. The younger in age one has a diagnosis of NAFLD, the more one can expect to have a drop in life expectancy. Hannes suggests this may summon an urgency in screening younger populations. A caveat of this cohort is noted to be the reality of true incidence rates could be higher than what has been captured in diagnosis in specialty care. At this point, Jörn and Louise ask a series of thought-provoking questions which spur Hannnes to describe additional compelling facets of working with this rich data set. Studies can link research cohorts examining biopsies of patients with NAFLD to these registers, allowing for long-term follow-up. Hannes also mentions collaboration with the Swedish Diabetes Register which captures at least 90% of patients with type 2 diabetes. Such granularity enables investigation into the influence of comorbidities on the risk of liver disease. Roger notes a theme of recent guidelines is to assume that diabetic patients have NAFLD, therefore the recommendation is to immediately search for NASH in the evidence of fibrosis. As these databases are pooled, NAFLD can be examined through a diabetes lens or vice versa. The group goes on to briefly discuss elements of screening, guidelines and the influence of NITs on interpreting prevalence. Hannes bridges this discussion to a just-accepted paper whereby his team looked at developing FIB-4 in a more meaningful way through stratifying subgroups within the overarching risk categories. Simply, the three parameters used are age, presence of diabetes and a gamma-glutamyl transferase test. The latter is noted to be useful in linking cardiac outcomes and an imperfect marker for alcohol use.
As the session winds down, the panelists explore speculative questions around genetics and the microbiome, and any foresight into how these factors could be filtered through the aforementioned registers and databases. In closing, Hannes provides a glimpse at what awaits for his research in 2023. Surf on to find out.
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In the Season 3 NAFLD Year-in-Review conversationsseries, Surfers Jörn Schattenberg, Louise Campbell and Roger Green embark on a string of interviews with a handful of Key Opinion Leaders who made headlines and advances in Fatty Liver disease in 2022. In this exclusive segment, Scott Friedman joins to discuss his perspective on what has been an eye-opening year for liver science.
Scott prefaces this session with the idea that in the absence of an approved drug, the field has responded with an urgency to develop improved pathways and targets. This urgency is coupled with progressive efforts to modify and improve clinical trials and endpoints, and noninvasive markers to make those trials more streamlined and accessible. From here he introduces illuminating findings on genetic variants associated with protection from Fatty Liver disease. An attention-grabbing conclusion: rare germline mutations in the CIDEB gene conferred substantial protection from liver disease. Scott states the implications are twofold. This summons recognition of the power of genetics in uncovering new pathways. This also highlights the complexities of a disease featuring genetic variants that may variably contribute to the likelihood that a patient with obesity develops NASH. He suggests that broadly, the challenge in NASH is sifting through an enormous palette of drivers - be it genetic, derived from the microbiome, or attributable to diabetes and the consequences of metabolic syndrome. All of which influence how we decide to establish and prioritize strategies for the discovery of new therapeutic targets. Reinforcing his recent comment on the podcast that gene therapy has effectively arrived, he notes the speed by which genetic information can translate into real therapies.
Continuing on the theme of scientific advancements, Scott points to papers emerging from the Columbia University lab of Robert Schwabe. The aim of the Schwabe lab is to understand the regulation of wound healing responses to chronic liver injury with a specific focus on how the activation of hepatic stellate cells (HSCs) promotes liver fibrosis and liver carcinogenesis. Scott raises a spate of compelling questions in response to Schwabe’s interrogation and subsequent findings on functions of HSCs, the main source of liver fibroblasts, during hepatocarcinogenesis. He accredits the feasibility of these studies back to the emerging availability of single cell sequencing technologies. Once again, Scott reveals his acceptance that the “devil is in the details,” alluding to the back-and-forth switching capacity of particular cellular functions. By identifying the transcription factor that drives this switching to a protective role, Scott suggests there is potential to enhance the expression of that transcription factor using gene therapy. Whether we can realistically expect to change the behavior of cells in the setting of an injured liver through the manipulation of gene expression is something to look forward to. “The best is yet to come.”
The group breaks into a brief discussion around the stepwise commercial progression and eventual success of Hepatitis C treatment. As the interview winds down, Scott returns to one last paper of interest stemming from his own laboratory and set to be published in the imminent future. The focus of the paper postulates stage-specific therapies as NASH develops. While admittedly “a long way off” from a clinical setting, this project framework injects Scott with invigoration to address possibly the largest unmet need of patients who have or are approaching cirrhosis. Surf on to his upcoming NASH-TAG talk for a more explicit demonstration of thi
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The latter half of December marks the Surfing the NASH Tsunami annual NAFLD Year-in-Review. In Part 1 of this Season 3 finale, Surfers Jörn Schattenberg, Louise Campbell and Roger Green interview Scott Friedman, Hannes Hagström and Donna Cryer to discuss putting a dent in Fatty Liver disease in 2022 and beyond. This episode features compiled excerpts from our respective guest interviews. Each interview in its entirety will debut as this week’s conversations, releasing Friday through Sunday.
Surf on to hear the diverse and powerful perspectives provided by a handful of the field’s Key Opinion Leaders who made headlines and advances in Fatty Liver disease in 2022.
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This week, our conversation From the Vault features a special, single-interview episode to give listeners a chance to learn about Jörn Schattenberg in a different way as he became the permanent Key Opinion Leader on Surfing the NASH Tsunami earlier this year.
The Surfing the NASH Tsunami seasons start with the calendar year, but our first episode posted on April 15, 2020. As we embarked on our third year, we wanted to give listeners a chance to get to know Jörn Schattenberg a bit differently than you would just from listening to episodes. Jörn discusses how he decided to become a hepatologist, why Stephen Harrison’s phrase “Greet ’em and Street ’em” has such resonance, the basic science work his laboratory in Maïnz does, and where he sees the podcast fitting into the future of Fatty Liver disease. Louise Campbell and Roger Green ask questions and share viewpoints in this fast-moving, two-part conversation.
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This week, our conversation From the Vault features a special, single-interview episode to give listeners a chance to learn about Jörn Schattenberg in a different way as he became the permanent Key Opinion Leader on Surfing the NASH Tsunami earlier this year.
The Surfing the NASH Tsunami seasons start with the calendar year, but our first episode posted on April 15, 2020. As we embarked on our third year, we wanted to give listeners a chance to get to know Jörn Schattenberg a bit differently than you would just from listening to episodes. Jörn discusses how he decided to become a hepatologist, why Stephen Harrison’s phrase “Greet ’em and Street ’em” has such resonance, the basic science work his laboratory in Maïnz does, and where he sees the podcast fitting into the future of Fatty Liver disease. Louise Campbell and Roger Green ask questions and share viewpoints in this fast-moving, two-part conversation.
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Surfing the NASH Tsunami begins its year-end series to reflect on a momentous 2022 for NAFLD and Season 3 of the podcast. Leading this final conversation, Roger Green asks Jörn Schattenberg what has surfaced in the past several months with the various consortia, and particularly the retrospective analysis in NAIL-NIT. Jörn starts by commenting that non-invasive testing may have more momentum now than any other areas in research. He notes the increasing number of consortia and the role they play in shaping the scope of NITs. One impact has influenced change in the original focus of how NITs could replace biopsies. The shift explores how NITs can be validated by histology via reductions in ALT, MRI-PDFF and MRE metrics. For particular data of interest, Jörn goes back a year to a study from the NASH CRN that measured severity in terms of baseline histology and then produced ratios of decompensation at different fibrosis stages. He goes on to explain that data from the single-sponsor studies, such as the resmetirom MAESTRO data, produces faster results than the larger consortium studies. Louise Campbell asks whether or how we can measure the impact of patient behavior change on outcomes in these studies. Jörn notes that the researcher can include questionnaires and app-based assessments to accommodate these factors.
At the bottom of the hour, Roger asks the group for final thoughts on changes envisioned for the next year specifically in terms of pathways. Each panelist provides thought-provoking responses to presage what is aligned to be another progressive year for the field in 2023.
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Surfing the NASH Tsunami begins its year-end series to reflect on a momentous 2022 for NAFLD and Season 3 of the podcast. In this conversation, Surfers Jörn Schattenberg, Louise Campbell and Roger Green continue to share their respective highlights.
Louise and Jörn begin by discussing some of the benefits of FibroScan in terms of how practitioners have come to use data more appropriately with the newer iterations of the product. As Louise points out, older machines tracked kilopascals only. This could help identify disease but not support liver health as effectively. Newer machines measure liver stiffness, providing more nuanced insights into overall health. Jörn raises a question: why test when virtually everyone with liver disease has NAFLD? He suggests a test offers inexpensive therapy in the form of enhanced patient education and self-care. Louise mentions from her experiences in Australia that people even forget the role the liver plays in metabolism. She emphasizes this is in a country where the Aboriginal populations have such exceptional documentation about liver disease and education tools, both of which Louise describes in some detail. Jörn speculates that FibroScan use in the German system will continue to be limited due to low levels of reimbursement, unless there is a patient co-pay. Louise speculates that costs will come down, using her experience in the UK to support her suggestion.
The remainder of the conversation stems from Roger’s question about how digital tools will integrate with FibroScan over time. Louise believes they can work together in driving patient motivation. From a different view, Jörn suggests that in the German system, where data transfer is highly inefficient, practitioners will be challenged to integrate the data from these tools into patients records. As a result, it will remain difficult to integrate the tools themselves into patient care. Lastly, Roger notes that electronic health record systems can essentially eliminate this issue, however someone needs to pay for developing them.
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Surfing the NASH Tsunami begins its year-end series to reflect on a momentous 2022 for NAFLD and Season 3 of the podcast. In this conversation, Surfers Jörn Schattenberg, Louise Campbell and Roger Green share their respective highlights.
All three agree that a return to in-person meetings offered both opportunities to reconnect and meet for the first time those who have been part of the podcast since launching in 2020. This leads Jörn to harken back to how the role of the podcast changed through the duration of the pandemic. At the outset, it was possibly one of the only places for colleagues to exchange and engage in regular discussion about pivotal medical issues. Today, he notes, while colleagues can once again meet fairly regularly at different meetings, the podcast remains a source of excitement and valuable discourse. Roger points out that the transition to on-site meetings actually coincided with a rise in listenership. This rise is attributed to the explosion of knowledge about drugs, devices and pathophysiology alongside burgeoning discussions around guidelines and care pathways.
The discussion next focuses on an announcement from Louise that NICE is expected to approve FibroScan for primary care under specific circumstances. In light of this news, the trio take a minute to review the history and process by which NICE came to modify its initial position on the subject. Jörn notes that FibroScan is not only a tool for detecting liver disease, but also that it provides patients with a way to improve liver health. As the conversation winds down, Louise, who is recording in Perth, describes that FibroScan use in Australia is late and limited, possibly contributing to the country’s rapid rise in NASH prevalence.
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Surfers Jörn Schattenberg, Louise Campbell and Roger Green host the Season 3, Year-in-Review episode to reflect on major themes and takeaways from a momentous 2022 in NAFLD.
The trio begin by highlighting the rewarding return to in-person conferences and events, and meeting fellow surfers for the first time offline. In response to his stepping into the role of permanent co-host, Jörn comments on the value he has derived from engaging in the ongoing dialogue supported by podcasting - something that continues to excite him even as life reverts somewhat to pre-pandemic, face-to-face interactions. The transition to on-site meetings, Roger notes, actually coincided with a rise in listenership. This leads the group to suggest the density and quality of data emerging from the field as deserving of more space for discourse outside of meetings alone. Louise also points to the diversity of perspectives championed through these conversations. For her, bringing the strength of patients to pathway development is critical and something she enjoys tuning in for on the episodes where she is absent. Roger adds that this year, the platform has really broadened its scope beyond simply drugs.
Louise segues to the subject of non-invasive technologies, pointing to some new and exciting news: NICE is on its way to approve FibroScan for all primary care physicians in the UK, so long as the patient is in a liver pathway. This predominantly includes NAFLD, Hepatitis B and fibrosis over the age of 16. FibroScan is noted to often be confused with a radiology test and not properly recognized as a type of liver elastography. It is through education and the rewriting of a pathway that FibroScan can be effectively used to achieve earlier diagnosis in many more patients with liver disease, liver fibrosis and risk in metabolic health. Jörn suggests this breakthrough supports a cross-sectional correlation between driving wellness through patient lifestyle management and cutting costs, for example, through the reduction of incidence of diabetes. From a wider metabolic perspective, assessing health through liver fat is a powerful tool to be harnessed for patient empowerment and demonstrating the influence of lifestyle interventions.
The conversation continues to address the expanding aperture of insights available not only through FibroScan, but additional technologies contributing to patient empowerment. Digital apps amongst other tools hold the possibility to reinforce the recurring theme on this podcast that liver health needs to be measured and monitored in a preventative manner as opposed to an end-stage disease outcome. Roger and Jörn briefly discuss digital tools for automating and scheduling functions built within health care systems, comparing progress in Europe versus the US. Jörn adds that, provided feasibility regarding information security concerns, linking data on a holistic level would pave a tremendous step forward for the patient experience. Roger next shifts focus to ask Jörn for any updates on the NAIL-NIT retrospective analysis previously discussed in April. Jörn refers to his experience of contributing to the LITMUS Consortia and its aim to validate a biomarker to replace liver biopsy as an outcome in clinical trials. He notes both retrospective and emerging prospective data supported an improved understanding of how a biomarker is linked to histology, and how a changed biomarker is linked to a change in histology.
At the bottom of the hour, Roger asks the group for final thoughts on changes envisioned for the next year specifically in terms of pathways. Each panelists provides thought-provoking responses to presage what is aligned to be another progressive year for the field in 2023.
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Lars Johannson’s 2021 Paris NASH presentation, “Innovations in Imaging Assessment of Fibrosis“,” introduced his audience to a dynamic, multidimensional view of tools that can show us how the liver works. His viewpoint combined with discussion on novel imaging tools and approaches creates an episode From the Vault that might leave you repeatedly thinking “Oh, Wow!”
This conversation excerpt begins with a comment from Louise Campbell that this entire approach might play a significant role in moving us beyond the biopsy. Lars agrees, noting that studying fibrosis and fat reduction places too much emphasis on “what shouldn’t be'' in the liver instead of focusing on “what should be,” which are high functioning hepatocytes. To explore hepatocyte function, he discusses use of gadolinium contrast agents, more than 50% of which are taken up by hepatocytes. This provides a setting to combine dynamic functional inputs based on hepatocyte function with static measures based on stiffness and PDFF. This provides a truly dynamic look at liver disease, which is particularly important given the liver’s ability to regenerate. Stephen spends the last few minutes of the conversation discussing the results this approach can yield and contrasting it favorably to the techniques we use today, some of which are difficult to implement and none of which provide the richness of information achievable with the imaging techniques Lars describes.
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The Liver Forum aims to advance the regulatory sciences for the treatment of NAFLD/NASH and liver fibrosis by providing a neutral, independent venue for ongoing multi-stakeholder dialogue. Their work facilitates the best science-based decisions on how to study efficacy and safety in real-time by using collective knowledge and experience with therapies for advancing liver disease. In this final conversation, Executive Director Veronica Miller joins guest Manal Abdelmalek and co-host Jörn Schattenberg (both Steering Committee members) to discuss the Liver Forum, its unique processes and valuable work.
Roger Green starts this conversation suggesting that the findings of the Placebo Arm Database Project need to translate into guidelines for researchers to formally standardize. Veronica describes elements of how the Forum is organizing the trial and what she considers some of the critical success factors for a placebo cohort. She notes this should benefit individual pharmaceutical sponsors because they can assess data in the context of placebo response and how to recruit patients for clinical trials. She also believes that if these metrics are feasible to implement, they will find ways into clinical practice as well. Manal notes that another benefit might be to give regulators access to larger data sets that mirror how the trials are done, leveraging resources and providing benchmarks at the same time. Jörn notes the Forum to be an open process and provides examples of what he considers to be some key benefits to this. Veronica concludes the main conversation by discussing the idea that a shared placebo arm might be possible and would have tremendous benefit. Roger poses the final question: each panelist provides the strongest takeaway for what they hope listeners glean from this episode. Surf on to find out more.
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The Liver Forum aims to advance the regulatory sciences for the treatment of NAFLD/NASH and liver fibrosis by providing a neutral, independent venue for ongoing multi-stakeholder dialogue. Their work facilitates the best science-based decisions on how to study efficacy and safety in real-time by using collective knowledge and experience with therapies for advancing liver disease. Previously, Executive Director Veronica Miller had introduced ongoing work with the Placebo Arm Database Project, co-chaired by Manal Abdelmalek.
Jörn Schattenberg leads this conversation with the observation that in Manal's past appearances on the podcast, she has discussed the value of stabilizing disease. Jörn asks whether the Forum is creating new insights on that front. Manal circles back to the challenges presented by an inability to predict an a priori placebo response rate and several issues in managing samples through trials. She notes that if researchers can integrate placebo arms from multiple trials, this will lead to far larger data sets. Additionally, this will strengthen the ability to create deeper insights and more robust solutions to issues surrounding the best way to manage and standardize these trial elements. From here, Jörn’s question shifts focus toward composite trial endpoints. After a brief discussion on this issue, the conversation turns to the value of AI and better controlled study analysis. Roger poses a question regarding reducing placebo rates. Manal suggests that the goal is not to lower placebo rates, but instead to standardize them in the most accurate ways possible. The conversation concludes with Jörn noting that he is constantly concerned about whether he is matching patient and trial to maximum benefit.
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Previously, Executive Director Veronica Miller explained how she arrived to the field of NAFLD and the history of the Liver Forum. This conversation begins with recollections from Manal Abdelmalek and Jörn Schattenberg on their respective introductions to the Liver Forum. Before the collaborative space existed, Manal points out that when industry first began to ponder NASH drugs there were no road maps for trial design or endpoints. Jörn then describes his first attendance of a Liver Forum meeting. He found the experience to be uniquely valuable for its welcoming diversity of stakeholder inclusion and participation. Today, he is on the steering committee.
The remainder of the session revolves around the panelists’ responses to questions from Roger Green, beginning with the intentionality behind using the word “forum” to represent their work. Following, Veronica discusses an ongoing project aimed to develop research tools and metrics that can capture the richness available in a plethora of data emerging from NASH studies. She envisions the field of omics to potentially illuminate a myriad of patient-specific biomarkers. Comparatively, she deems the biopsy a “very blunt tool.” She goes on to note that the COVID-19 pandemic complicated the challenges of conducting trials and developing data. Stakeholders are now returning to sieve through huge quantities of emerging data, distilling them into lessons that will shape how we diagnose and treat Fatty Liver patients. At the end of this session, Veronica begins to introduce the Placebo Arm Database Project, co-chaired by Manal.
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The Liver Forum aims to advance the regulatory sciences for the treatment of NAFLD/NASH and liver fibrosis by providing a neutral, independent venue for ongoing multi-stakeholder dialogue. Their work facilitates the best science-based decisions on how to study efficacy and safety in real-time by using collective knowledge and experience with therapies for advancing liver disease. In this conversation, Executive Director Veronica Miller describes how she arrived to the field of NAFLD and the history of the Liver Forum.
Veronica begins by sharing the story of her background, originating in primary research in immunology. This led to her landing in Washington DC to assume leadership of the Forum for Collaborative HIV Research. Veronica recalls this experience as setting precedent for the potential that a forum could be and accomplish. The idea of the HIV Forum was for all stakeholders - patients, drug developers, physicians, investors, regulators and government agencies - to convene for a collaborative approach to research in a safe, egalitarian environment. For Veronica, it was a major switch from presenting her own data to masterminding and leading this collective approach to deal with addressing research gaps. Notably, the role required her to bring disparate groups together, including HIV patient activists, who were extremely knowledgeable and at times challenging. Critically, the forum experience leant patient voice to the arena for the first time. Within a few years, that same approach was expanding to other disease areas, including Hepatitis C. Through the Hepatitis C Forum, Veronica worked to resolve the issue of creating a clinical trial without standard controls. After attending a meeting at FDA about clinical trial endpoints, she ventured into the field of Fatty Liver disease. The session concludes with her note that NAFLD is unique from other diseases in that Fatty Liver does not have a pathogen to target.
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The Liver Forum aims to advance the regulatory sciences for the treatment of NAFLD/NASH and liver fibrosis by providing a neutral, independent venue for ongoing multi-stakeholder dialogue. Their work facilitates the best science-based decisions on how to study efficacy and safety in real-time by using collective knowledge and experience with therapies for advancing liver disease. In this episode, Executive Director Veronica Miller joins guest Manal Abdelmalek and co-host Jörn Schattenberg (both Steering Committee members) to discuss the Liver Forum and its valuable work.
Veronica details her fascinating, well-traveled background and the path she has taken from HIV research to the HIV Forum - an experience that defined what a forum could be and do - to work on HCV and eventually NAFLD. After Veronica describes her path to the Liver Forum, Manal and Jörn share theirs. Each panelist is attracted to this opportunity to pool insights and ponder the deepest, most challenging questions in liver disease with colleagues from across a broad range of stakeholder organizations.
The conversation shifts from how the Liver Forum came to be to its ongoing activities and programs of today. Veronica believes the striking challenge of the NASH paradigm to be surmounting sufficient evidence to move beyond the liver biopsy. Recalling the precise and dynamic developments of biomarkers for HCV and HIV, she notes the fatty liver field struggles in absence of a pathogen. There remains a new set of complexities regarding disease etiology and pathophysiology, the natural course of disease and the resulting divergent strategies for therapeutic approaches. However, she points enthusiastically to the emerging field of omics for its potential to illuminate a myriad of patient-specific biomarkers.
As we all move beyond the logistical limitations imposed by the COVID-19 pandemic, stakeholders can now come together to sieve through huge quantities of emerging data and distill them into lessons that will shape how we diagnose and treat Fatty Liver patients and then monitor the outcomes of these activities. As the panel notes, data collaboration is a key component for such a paradigm shift. Veronica introduces the Placebo Arm Database Project, co-chaired by Manal, whereby completed trials are studied in an effort to determine what predicts the stability of disease versus progression or improvement. Manal elaborates on the efforts made toward understanding placebo cohorts in totality, including predictors of responsiveness and adherence amongst other sources of variability. By pooling a wider net of datasets, she hopes to draw stronger conclusions, assessments and even benchmarks to power and design more effective trials in the future. Jörn comments that while he is interested in the influence of background care, he wonders whether by combining two histologic endpoints, fibrosis regression and NASH resolution, placebo response is effectively reduced. Manal suggests the field needs either an all-encompassing drug or to make allowances to tease out the risks, benefits and alternatives of unique therapies. She then expands on how an understanding of placebo arms can optimize patient selection for trials. From here, Veronica bridges the conversation to include the influence these insights might have on driving drug development before venturing into the imminent future of clinical trial design.
This episode offers a very special glimpse into the conversations and considerations taking place in the background of putting a dent in fatty liver disease. The session ultimately exposes a fascinating window into the creative thinking applied to the varied, complex challenges facing the field.
This episode From the Vault follows Season 2, Episode 43 in discussing the possible role of NASH cirrhosis clinical trials in the transition from biopsy as gold standard to a post-biopsy world. Terns Pharma CEO Sen Sundaram joins this conversation from the audience to ask whether the term “cirrhosis” is medically helpful or might warrant replacement with “end stage liver disease.” After vigorous discussion on this point, Sen departs and Stephen Harrison leads the group through a review of four ongoing NASH cirrhosis trials. The discussion veers into the issue of which analytics methods designers are specifying and why. At one point, Naim Alkhouri, frequent guest and principal investigator on the Gilead combination agent trial, comments before the session ends. His specific contribution: MRE was not included in the Gilead trial largely for cost reasons.
The most striking fact to emerge from this conversation relates to the “beyond the biopsy” question. MRE is emerging as a highly reliable NIT that appears to produce reliable results regardless of mode of action and is generating correlations and ratios to fibrosis level decreases and other key metrics, yet it is not included in the designs of any ongoing NASH cirrhosis trial. Stephen describes this as the “stovepiping” of data. Companies consider the data they need, not ways it can be aggregated with other trials to solve larger issues. This issue bears further exploration in later episodes.
Surfing the NASH Tsunami hosts its first episode dedicated to nutrition and NASH with distinguished guest, Prof. Shira Zelber-Sagi. Alongside this rich discussion are Ken Cusi, Jörn Schattenberg, Louise Campbell and Roger Green.
This final conversation starts with Jörn recalling Shira's statement that “diet is every day.” He notes that for patients whose serious medical issues are related to poor diet and lifestyle choices, behavior and diet can play an integral role in improved patient self-care and overall health. Roger highlights that a combination of medications and self-management can be a powerful, reinforced and effective treatment solution. This leads Shira to provide a step-by-step vision of how to work with patients on improving bad habits. In the end, she notes, clinicians and leaders need to appreciate the importance of policy in supporting clinical goals. The conversation continues with the group discussing what Louise calls “fun facts” about common unhealthy foods. For the final question, Roger asks the panelists for one piece of advice to be utilized by providers seeking to push behavioral change in their patients. Surf on for their key takeaways.
Surfing the NASH Tsunami hosts its first episode dedicated to nutrition and NASH with distinguished guest, Prof. Shira Zelber-Sagi. Surfing alongside this rich discussion are Ken Cusi, Jörn Schattenberg, Louise Campbell and Roger Green.
Ken begins this conversation by extending his ideas around the need for US insurance companies to support integrated solutions. Louise asks Ken whether he believes things will change when new anti-NASH drugs are approved. Ken states that in his dealings over the years with insurance companies, obesity management has been regarded as an expense, not an investment. He notes Western democracies in general have neglected to invest in obesity management.
Roger revisits the theme of finding value in apps and digital interventions. Shira believes that while they can be a helpful tool for many, they cannot replace human interaction. Ken agrees and elaborates that while an app can catalyze momentum, motivation often wanes after several months. Those trying moments are exactly when Ken envisions human intervention to be critical. Jörn returns to the idea that patients need to develop the habit of regular dietician visits. He says he might adopt Shira’s “haircut” metaphor, whereby maintenance visits are conducted every month or two. As the conversation winds down, Louise and Shira discuss the idea that while allied providers do not have the time for full-fledged behavioral therapy, they can provide information and support that helps patients improve.
Surfing the NASH Tsunami hosts its first episode dedicated to nutrition and NASH with distinguished guest, Prof. Shira Zelber-Sagi. Surfing alongside this rich discussion are Ken Cusi, Jörn Schattenberg, Louise Campbell and Roger Green.
Roger prompts this conversation by stating that everyone eventually makes poor dietary choices. The group agrees through various examples that the key is to not let a momentary shortcoming deter progress along the wellness journey. Shira emphasizes that relapse is part of the process and ought to be factored into patients' long-term plans. She goes on to disclose her love for chocolate and how patients can still have some of their favorite foods in their new diet. This leads Ken to describe diet as simply one aspect of a full-life balancing act. For him, perfectionism is the enemy. The group goes on to consider the psychology of decision making around diet in similar terms to that of addiction treatment. Louise notes that while the field of NAFLD deals with areas requiring immense psychological support, those resources are lacking for patients. In addition to including a dietician on the team, she adds emphasis to the benefit of cross-training physicians with education on mental health support. Ken agrees and comments that the US insurance system makes it hard for patients to get the collateral support they need.
Surfing the NASH Tsunami hosts its first episode dedicated to nutrition and NASH with distinguished guest, Prof. Shira Zelber-Sagi. Surfing alongside are Ken Cusi, Jörn Schattenberg, Louise Campbell and Roger Green to discuss effective goal setting and dietician visits as life-long therapy.
This conversation continues on the subject of weight reduction for NASH resolution. Previously, Jörn, Ken and Louise walked through their ideas on strategies around long-term self-management in implementing a healthy diet. Shira begins by describing her own approach, termed weight-inclusive, which focuses on holistic coaching measures that extend to all facets of a happy and healthy lifestyle. By including tools like exercise with all other reachable means of positive feedback, patients are relieved from becoming too fixated on weight-loss. This approach also integrates setting and driving realistic goals, and dietician visits as a life-long therapy. Shira relates visits to the dietician to be as simple as returning for a haircut every month or two. Jörn comments on the value of biofeedback and highlights the ability to drive better health through digital tools. Shira is optimistic about the potential, but cautions negative feedback can also be detrimental to progress. As the session winds down, she describes the power of relationships formed between dieticians and patients on their wellness journey towards regression.
Surfing the NASH Tsunami hosts its first episode dedicated to nutrition and NASH with distinguished guest, Prof. Shira Zelber-Sagi. Surfing alongside are Ken Cusi, Jörn Schattenberg, Louise Campbell and Roger Green to discuss weight reduction for NASH resolution, and strategies for long-term adherence to lifestyle modifications.
Shira leads this conversation by introducing the topic of weight reduction as a first line of defense for the field of NAFLD. While discussing weight loss targets for patients with different degrees of Fatty Liver disease, it’s identified that ≥7% weight reduction is a “golden number” for patient resolution. In terms of how weight reduction is achieved and maintained, it is noted that long-term adherence to lifestyle modification poses significant challenges. Choosing the right diet for a diverse population of patients can be daunting. Before disclosing her own ideas, Shira asks for the group’s approach to the topic. Jörn suggests hepatologists are not particularly effective at assessing diets or prescribing specific solutions. As such, he adheres to simple protocols like intermittent fasting. Jörn also asks a question to the group that he receives often: Why is there a need for drugs in this disease if patients just need to lose weight? Ken notes that in the US, excess caloric intake can be treated with the prescription of weight-loss medications, like a GLP-1, or more NASH-specific agents, like pioglitazone. He also suggests endocrinologists are better equipped to provide education on nutrition to patients. The group agrees that partnering with a nutritionist is invaluable for developing strategies around long-term self-management. Finally, Louise shares her belief that successful solutions begin with small, achievable goals.
In a timely debut during the American Thanksgiving holiday, Surfing the NASH Tsunami hosts its first episode dedicated to nutrition and NASH with distinguished guest, Prof. Shira Zelber-Sagi. Surfing alongside in this rich discussion are Ken Cusi, Jörn Schattenberg, Louise Campbell and Roger Green.
After sharing how she came to the intersection of nutrition and NASH, Shira leaps into the topic of weight reduction as a first line defense for the field of NAFLD. While identifying ≥7% weight reduction as a “golden number” for patient resolution, it’s noted that long-term adherence to lifestyle modification poses a significant challenge. Choosing the right diet in a diverse population of patients also poses a significant challenge. Jörn suggests hepatologists are not particularly effective at assessing diets or prescribing specific solutions. As such, he adheres to simple protocols like intermittent fasting. Ken comments that endocrinologists are better equipped to provide education on nutrition to patients. He notes that in the US, excess caloric intake can be treated with the prescription of weight-loss medications, like a GLP-1, or more NASH-specific agents, like pioglitazone. Louise adds that successful solutions begin with small, achievable goals.
Shira goes on to describe her own approach, termed weight-inclusive, which focuses on holistic coaching measures that extend to all facets of a healthy lifestyle. By including exercise with all other reachable means of positive feedback, patients are relieved from becoming too fixated on weight-loss. This approach also integrates setting and driving realistic goals, and dietician visits as a life-long therapy. Shira relates visits to the dietician to be as simple as returning for a haircut every month or two. She also suggests any healthy diet that works for the patient is permissible. Jörn comments on the value of biofeedback and highlights the ability to drive better health through digital tools. Shira is excited by the potential, but cautions negative feedback can be detrimental to progress.
Roger states that the reality of failure is unavoidable: everyone eventually makes poor dietary choices. The group agrees the key is to not let a fleeting shortcoming deter progress. From here they consider the psychology of decision making around diet in similar terms to that of addiction treatment. Louise notes that while the field of NAFLD deals with areas requiring immense psychological support, those resources are lacking for patients. Ken adds that working interprofessionally with dieticians is not well supported by insurance companies in the US. He states that in his dealings with insurance companies, obesity management has generally been regarded as an expense, not an investment.
Roger revisits the theme of finding value in apps and digital interventions. Shira believes that while they can be a helpful tool for many, they cannot replace human interaction. Ken elaborates that while an app can catalyze momentum, motivation often wanes after several months. Those trying moments are exactly when he envisions human intervention to be critical. Recalling Shira’s statement that “diet is everyday,” Jörn emphasizes that behavior and diet can play a key role in improving patient self-care and overall health. Roger highlights that a combination of medications and self-management can be a powerful, reinforced and effective treatment solution.
Shira provides a step-by-step vision of how to work with patients in improving bad habits. She notes clinicians and leaders need to appreciate the importance of policy in supporting clinical goals. For the final question, Roger asks the panelists for a piece of advice for providers seeking to push behavioral change in their patients. This is a fun, applicable and endlessly important topic to be explored. Surf on to learn more!
Thursday, June 9, marked #NASHDay 2022, the 5th annual celebration of International NASH Day by the world’s largest liver patient advocacy organization, the Global Liver Institute. For the #NASHDay Wrap-up Panel, Global Liver Institute invited NASH Tsunami co-hosts Jörn Schattenberg, Louise Campbell and Roger Green to join NASH Programs Director Jeff McIntyre to discuss themes of the day and major issues in the Fatty Liver community.
This conversation includes the last fifteen minutes of the GLI NASH Day wrap-up panel. Jeff McIntyre asks two questions to the group. First, he asks each panelist to respond to the slogan #StopNASHNow and its implication that for patients, it might be enough simply to arrest the progression of fibrosis. Therefore we should devote efforts in research and regulatory energy to stopping the progression instead of focusing entirely on regression. For his last substantive question, he asks each of us to discuss something that puts a twinkle in our eyes as we consider the next 3-5 years of progress in the fight against Fatty Liver disease. Surf on for great questions that yield interesting and diverse answers.
Given the vast amount of information and insight from The Liver Meeting, this episode sought to identify and explore a few key highlights. The panel (Jörn Schattenberg, William Alazawi, Naim Alkhouri, Laurent Castera, Ken Cusi, Wayne Eskridge and Roger Green) addresses several topics from the program.
This final conversation examines the diversity of populations with NASH and other ways we can learn from and about them. Naim begins by discussing work with pediatric NASH, specifically noting the shortcomings of NITs for these patients. Ken and Roger note the diverse forms of NASH, including both lean and pediatric, that are receiving increasing attention. Roger also recalls the SPLENDOR Study and what it tells us about the ability of bariatric surgery-driven 20% weight loss to regress fibrosis in non-cirrhotic patients. The group touches briefly on Scott Friedman’s observation from last week's coverage about the impact of environmental factors on the microbiome and how that might affect these metabolic issues.
Roger closes by asking the group for one thing, besides a drug approval, that will change how we think about or treat this disease in the next year. Surf on to discover their predictions.
Given the vast amount of information and insight from The Liver Meeting, this episode sought to identify and explore a few key highlights. The panel (Jörn Schattenberg, William Alazawi, Naim Alkhouri, Laurent Castera, Ken Cusi, Wayne Eskridge and Roger Green) addresses several topics from the program.
Naim begins this conversation with mentioning Labcorp’s announcement that a reflex ELF test is available for patients with high FIB-4. The latter will be computed if the patient has a complete blood count (CBC) and a comprehensive metabolic panel (CMP). As Naim notes, this is similar to the Hep C paradigm where patients with a positive Hep C antibody test receive the Hep C RNA. For Naim, this is “a game changer” in primary care where patients with the basic CBC and CMP results can be flagged for advanced fibrosis using two widely-studied NITs.
Will segues to discuss John Dillon’s work with the intelligent Liver Function Test (iLFT), which was covered on the podcast earlier in the year. Since then, an abnormal iLFT result now leads to an ELF test. Like the Labcorp program, this follow-up makes it easier for primary care to identify patients with abnormal livers. Will cautions that more research on different ethnicities and disease levels ought to be conducted. At this point, Will exits the discussion due to a poor internet signal. While signing off he raises one last trend that has likewise surfaced on the podcast earlier this year. The encouraging note is that researchers are working to link NITs directly to outcomes instead of biopsy.
In the remainder of this session, Ken discusses advances in the use of PPARs. He first notes the ongoing work with the pan-PPAR, lanifibranor, followed by Poxel’s work with PXL-065. The latter is a deuterium-stabilized form of pioglitazone that generates greater activity of the r-enantiomer and less of the s-enantiomer. These are linked to mitochondrial benefit versus weight gain, respectively. Stephen Harrison discussed this molecule early last month in review of a recent string of press releases presaging some of the most promising data of the last decade in NASH drug development.
Given the vast amount of information and insight from The Liver Meeting, this episode sought to identify and explore a few key highlights. The panel (Jörn Schattenberg, William Alazawi, Naim Alkhouri, Laurent Castera, Ken Cusi, Wayne Eskridge and Roger Green) addresses several topics from the program.
This conversation focuses on several papers of interest to Laurent. The first is a prospective screening study on patients with diabetes seen in either primary care or a diabetes clinic in the US. Using NITs to screen for NASH and MRE to screen for advanced disease, they identified 65% with NAFLD, 14% with advanced fibrosis and 5% with cirrhosis. When 164 of these patients moved into biopsy, they identified 61% with NAFLD, 30% advanced NASH and 9% cirrhosis. Laurent contrasts these results to a similar study conducted in a French diabetes clinic-treated cohort with transaminase greater than 20 in women and 30 in men. This yielded 58% NASH, 38% advanced fibrosis and 10% cirrhosis.
The panelists then explore the implications of both studies in terms of how screening should be conducted today. Laurent estimates that we might miss ~25% of advanced patients using current VCTE cutoffs without additional parameters. He also notes that neither duration of diabetes nor A1c levels were predictive. The group concludes that, as Ken puts it, studies like these push the needle toward action in both primary care and diabetes settings.
Given the vast amount of information and insight from The Liver Meeting, this episode sought to identify and explore a few key highlights. The panel (Jörn Schattenberg, William Alazawi, Naim Alkhouri, Laurent Castera, Ken Cusi, Wayne Eskridge and Roger Green) addresses several topics from the program.
Ken leads this conversation with an analogy from the diabetes field. He describes the impact of albumin screening in urine on helping primary care treaters focus on diabetes screening and, ultimately, providing better information to patients. He shares his hope that a simple test, like FIB-4, will illuminate direction in the recent guidelines for liver diagnostics. Will suggests a few additional challenges face Fatty Liver disease. Treaters have one hand tied behind their backs because basic blood panels and screens do not provide the information necessary for algorithms to seamlessly assess liver health. He adds that “not having that information at your fingertips is one thing, but not knowing what to do with it afterwards is something else.”
Ken notes most patients in the US healthcare system receive an annual metabolic profile which often includes liver enzymes and a complete blood count. As such, he emphasizes the importance of educating on how to build the right equations into medical records. Roger notes a significant barrier: the US is one of the only countries whereby AST is standardized. It is frequently implored on this podcast that patient advocates outside the US make standardized testing for AST a priority. This is especially important for all diabetic patients.
Laurent Castera describes the French system which provides free medical checkups, but does not measure for AST. He suggests a problem that in France, doctors generally still link cirrhosis to alcohol and not NASH. As a result, they may not see the value in screening patients who do not consume alcohol. It’s noted that identifying patients with advanced fibrosis is critical even in the absence of pharmacological treatment. Ken points out that there are drugs for obesity and diabetes that also help in NASH, like pioglitazone and the GLP-1 agonists. With steps to help patients beyond diet and exercise, it is important to educate primary care to test for NASH.
As the conversation winds down, Naim provides two pieces of encouragement. The first, from a resmetirom open-label cirrhosis study, suggested that the drugs in development and close to market today may provide benefit for cirrhotic patients. The second, more encouraging to payers, came from a study he conducted with colleagues to assess how much burden the AGA pathway would place on the US system. The result: only 8% of patients would need to be treated by a hepatologist. This suggests that even with nearly 100 million people with NAFLD, only 4-5 million would require expensive NASH drugs.
Given the vast amount of information and insight from The Liver Meeting, this episode sought to identify and explore a few key highlights. The panel (Jörn Schattenberg, William Alazawi, Naim Alkhouri, Laurent Castera, Ken Cusi, Wayne Eskridge and Roger Green) addresses several topics from the program. This conversation focuses on an ongoing initiative of the Fatty Liver Foundation called the Annual Survey of Patient Perspectives.
Wayne introduces this 713-patient survey which sought to understand and monitor the evolving social and medical experiences of NAFLD patients in the US. The results of the study were presented at The Meeting. Notably, 80% of patients reported they were given either no or not enough information at diagnosis. One in three did not receive a referral to a specialist at diagnosis, and 60% of those who saw a specialist left the visit with little or no understanding of the disease. Wayne also notes a relatively small percentage of patients felt they were offered help at the time of visit in terms of diet and nutrition, or mental wellness as related to the diagnosis. Roger asks what would be the key message for treaters, pharma and diagnostic companies to take away. Wayne highlights two: patients are not well-informed or supported at time of diagnosis, and primary care providers lack the disease information and treatment insights to better support these patients.
As the session winds down, conversation shifts focus to consider the breadth of this physician challenge and address what remedial steps make most sense.
Given the vast amount of information and insight from The Liver Meeting, this episode sought to identify and explore a few key highlights. Even so, there is more in this episode than a brief summary can capture. The panel (Jörn Schattenberg, William Alazawi, Naim Alkhouri, Laurent Castera, Ken Cusi, Wayne Eskridge and Roger Green) address several topics from the program:
- Wayne presents information from a survey Fatty Liver Foundation conducted with NAFLD patients. The study reported that very few patients received adequate information at time of diagnosis, and one in three do not even receive a specialist referral. This sparks general discussion on how to drive stronger provider-to-patient communication. The group goes on to consider the value of testing and standardized score computation in medical records, which can improve screening and provider education to patients. One challenge here: AST, which is a key test in its own right and as part of FIB-4, is part of the standard test battery only in the US.
- In the minds of the panelists, provider information and education is and will remain a major challenge. Laurent notes that in France, providers associated cirrhosis with alcohol consumption, but not diet. Ken suggests that getting primary care providers to associate cirrhosis with fatty liver is a key step to improving screening and education.
- Naim points to the open-label resmetirom study with cirrhotic patients as providing “very promising results” in a range of non-invasive tests. He shares his enthusiasm that so many of the emerging guidelines rely on the same cut points in NITs. He goes on to discuss a study in which he and others evaluated the impact of using these guidelines (FIB-4 cut points, VCTE as second step, T2DM and metabolic patients as targets). Naim notes that if applied appropriately, the paper estimated only 8% of the US population would have any need to be treated by a hepatologist, and perhaps only 4-5 million would require intervention with expensive medications.
- Laurent shares a prospective screening study on patients with diabetes located in primary care settings or diabetes clinics based in the US. Using NITs to screen for NASH and MRE to screen for advanced disease, they identified 65% with NAFLD, 14% with advanced fibrosis and 5% with cirrhosis. When 164 of these patients moved into biopsy, they identified 61% with NAFLD, 30% advanced NASH and 9% cirrhosis. Laurent contrasts these results to a similar study conducted in a French diabetes clinic-treated cohort. The panelists explore the implications of both studies in terms of how should screening be conducted today. Jörn notes that we must consider the incentive for a physician to screen or enroll a patient.
- Ken discusses advances in the use of PPARs, noting first the ongoing work with the pan-PPAR lanifibranor followed by Poxel’s work with PXL-065. The latter is a deuterium-stabilized form of pioglitazone that generates greater activity of the r-enantiomer and less of the s-enantiomer. These are linked to mitochondrial benefit versus weight gain, respectively.
- Naim calls attention to the failing performance of NITs in pediatric NASH. Roger recalls the SPLENDOR Study (discussed on Season 2, Episode 60) and what it reveals of the ability for bariatric surgery-driven 20% weight loss to regress fibrosis in non-cirrhotic patients. Panelists then briefly discuss Scott Friedman’s observation from last week's coverage about the impact of environmental factors on the microbiome and how that might affect these metabolic issues.
Roger closes by asking the group for one thing, besides a drug approval, that will change how we think about or treat this disease in the next year. Surf on to discover their predictions.
Inventiva is a clinical-stage biopharmaceutical company that develops novel and differentiated oral small molecule therapies for patients suffering from diseases with significant unmet medical need.
In an exclusive interview, Inventiva's Chief Medical Officer Michael Cooreman joins Stephen Harrison and Roger Green to talk about the company. Specifically, Michael provides detail and color on key elements of the Inventiva clinical development strategy for its pan-PPAR, lanifibranor. The group also discusses the Phase 2b NATIVE trial, Phase 3 NATiV3 trial and combination trial with the SGLT2 inhibitor empagliflozin that had just begun to recruit.
Surf on for a rich conversation and learn more about this innovative company!
Over 7,000 in-person attendees from around the world convened at the 73rd Annual AASLD Liver Meeting for a lively and momentous event in Washington DC. Surfing the NASH Tsunami hosted two recording sessions throughout the event to discuss key takeaways. This conversation is a composite featuring impressions from both sessions.
The first session features Scott Friedman, Jörn Schattenberg, Rachel Zayas and Roger Green. Jörn starts this conversation by discussing a presentation delivered by Mazen Noureddin on the developmental mitochondrial uncoupler, HU6. While mitochondrial uncouplers are not new, they are to the field of NASH. Jörn goes on to describe a short, 61-patient trial. The trial yielded large percentages of patients reducing their liver fat more than 30% – around 40% at the lowest dose and 71 or 72% at the two higher doses – and HbA1C in a medication that appeared safe in this two-month trial. Scott goes on to credit Gerald Shulman at Yale for his role in developing knowledge about mitochondria and the liver. Jörn and Roger then recall Marcus Ranney, the self-described mitochondrial fan and biohacker, who discussed his affection for and belief in the importance of mitochondria during his talk in Barcelona and a subsequent NASH Tsunami interview. As the conversation wraps up, Jörn raises the idea that a mitochondrial uncoupler might be a short-term invention at the start of a longer therapeutic regimen. Scott notes that the idea of induction therapy vs. maintenance is gaining traction.
The second part of this conversation comes from a session on the final morning featuring Stephen Harrison, Sven Francque, Jörn Schattenberg, Ian Rowe, Jeff McIntyre and Roger Green. Roger begins with discussion of the REGENERATE trial, a Phase 3 from Intercept for obeticholic acid in non-cirrhotic NASH. Arun Sanyal presented a reanalysis of the results as a late-breaker on Monday. Roger describes the change in pathology-reading technology from the original analysis, in which the entire deck was distributed randomly between two readers. The two readers represented for the consensus and adjudication process in consideration. Slides where agreement could not be reached were not used. Roger reviews his take on the important elements of the results:
Improved resolution of what now appears to be transitory LDL elevations
A slight drop in placebo performance and slight increase in high-dose performance
The latter indicates the higher dose is roughly three times as effective as placebo instead of two-fold in the original analysis. Stephen continues to comment on the larger, vastly enhanced safety database in this study. Sven notes the study suggests there may be significant benefit in halting progression even in patients who do not regress.
Last month, Stephen Harrison joined the Surf to cover a recent string of press releases presaging some of the most promising data of the last decade in NASH drug development. As Principal Investigator, he reviewed Phase 2b results from Akero’s HARMONY Trial. This is a 24-week study evaluating the efficacy and safety of the FGF-21 agonist efruxifermin (EFX) in patients with clinically relevant NASH (F2-F3). The topline results he previously shared:
The study met its primary endpoint for both the 50mg and 28mg EFX dose groups.
Respectively, 41% and 39% of EFX-treated patients experienced at least a one-stage improvement in liver fibrosis with no worsening of NASH by week 24 (compared with 20% for the placebo arm).
In this follow-up conversation, Stephen walks through his presentation on the efficacy and safety of Akero’s lead product candidate EFX. After detailing the data, two important points emerge. First, Stephen and Sven Francque share the idea that “not all FGF-21’s are created equal.” FGF-21’s themselves need to be stabilized due to their two-hour half-lives. The first FGF-21, pegbelfermin, was PEGylated and revealed significant challenges in clinical development. EFX is a bivalent structure - two molecules stabilized by a fusion protein. This appears to work far better. The conversation continues with more points and questions about the study results and implications. An interesting idea surfaces: EFX might function better as an induction therapy to be followed by an oral maintenance therapy as a long-term monotherapeutic solution. As the session winds down, the group speculate the dynamics of what happens when disease regresses to a point where there is far less liver damage.
Sven Francque begins this conversation by discussing Laurent Castera’s paper comparing a range of NIT diagnostic tests: MAST, FAST, MEFIB, FIB-4 and NFS. When introducing the paper, Sven shares two items that Mazen Noureddin did not cover in an earlier preview. Professor Castera and his team used fairly low ALT cutoffs of 20 for women and 30 for men as the sole liver entry criterion for the study. The implication of this was to produce a relatively unbiased population sample in which more than 50% of patients exhibited NASH. Stephen Harrison joins to share data from his presentation on the FASN inhibitor that Scott Friedman referred to in the first review episode. Stephen describes that AI-based percent collagen computations in the FASN study indicated its highest correlation was with the FAST score. Additionally, MAST was comparable and AST alone holds significant power.
Roger Green looks to broaden the conversation by asking what we have learned about tests in this meeting. Ian Rowe summarizes the message he has derived from a range of studies to link the screening target - fibrosis vs. advanced fibrosis - with the value of a two-step testing strategy. As both Stephen and Mazen have suggested on recent episodes, Ian considers a compelling argument for moving straight to FAST. Roger expands that, as Professor Castera pointed out, the low gray zone number on the MAST test promises a far higher level of true positive and true negative results. It also promises significant cost savings in terms of reduced biopsy demand when screening for clinical trials. Ian builds on these considerations to make a final statement as this session winds down. If we have drugs available to treat patients in the community, providers need to become far clearer about diagnostic goals and then find the right test to link to each goal.
In this conversation, Jeff McIntyre leads with his impressions on the pan-society presentation of NAFLD nomenclature consensus process. He begins with an objective account of the parameters around an extensive Delphi process. Notably, Jeff points out that the discussion appears to be shifting away from the phrase “metabolic.” This is important because in many cultures and settings, “metabolic” may be no easier to explain to patients than “non-alcoholic,” although the specific challenges differ. Jeff also highlights that discussion appears to be moving away from redefining the target patient population. Any change in patient definition threatens to set back the ongoing clinical development work on drugs and diagnostics by a matter of years. Such a setback is clearly not in the interest of patients.
Jeff then engages in a critique of process elements that he felt were not supportive of patients. While every statement needed to surpass a two-thirds “supermajority” threshold to be incorporated in the consensus document, the group comprised more than 70% clinical researchers. If clinical researchers supported a statement heavily enough, no other group input would matter. He also notes the general sense of intimidation felt by patient advocates in the audience of the public debate. While the debate included 5-minute statements from GLI CEO, Donna Cryer, and PBC Foundation CEO, Robert Mitchell-Thain, advocates in the audience didn’t feel welcome to make any statements.
At this point in the conversation, panelists Stephen Harrison, Sven Francque, Jörn Schattenberg, Ian Rowe and Roger Green join to offer their perspectives:
Stephen describes Jeff’s passion as a breath of fresh air. Sven, who was quite involved in the process, responds with his experience and outlook. Jörn acknowledges this to be a complex challenge for the field and that there is no model to measure the potential consequences. Ian voices concern for “a real risk” in having alternate definitions without genuine consensus. Roger responds from his unique position of being neither a patient nor a physician.
Overall, the reactions are unique, interesting and varying. Surf on to hear their full takes.
Recorded onsite in Washington DC, Scott Friedman, Jörn Schattenberg, Rachel Zayas and Roger Green discuss takeaways from the first three days at the 73rd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD). The group encapsulates the dynamic, vibrant energy of returning to this momentous event which welcomed back over 7,000 in-person attendees.
Jörn starts this conversation by introducing a paper titled, The Effect of a Dual Receptor Glucagon-Like Peptide-1 and Glucagon Agonist, Cotadutide, on Serum Metabolome in Biopsy-Proven Non-Cirrhotic NASH with Fibrosis. He describes Cotadutide followed by the study design that added metabolomic analyses to more standard liver NITs. Serum metabolomics is an emerging non-invasive tool that may identify novel biomarkers for disease stratification and treatment efficacy. Jörn advocates for drug developers to consider adding metabolomic assessments to clinical trials.
Scott shifts focus to note that while our community is liver-centric, Fatty Liver disease is complex and therapies can affect other organs. He wonders how the benefit of these therapies may accrue from effects outside the liver, particularly muscle and adipose tissues. Rachel cautions that emerging gene therapies ought to evaluate the potential off target effects that might be introduced by silencing a gene expression in the liver. In agreement, Scott aptly responds that gene therapy has arrived. In an example from the COVID-19 pandemic, he highlights the development of finely tuned lipid nanoparticle carriers. Roger suggests there is considerable value in the approach of finding a solution, fixing the problem and then figuring out what happened.
The group continues on to discuss an abstract presented by Amrik Shah titled, Histologic Endpoints in NASH Clinical Trials: The Emperor Has No Clothes. This paper evaluated the effects of the imprecision of histologic reading and the consequent effects in therapeutic trials. Scott asserts the need for digital pathologies to enter the mainstream as endpoints in clinical trials. This sparks comments around Arun Sanyal’s redefinition of the REGENERATE data in Late Breaking Oral Abstract, Session 2. As the session winds down, Scott notes the licensing board in the US is no longer requiring liver biopsy as part of gastroenterology or liver training. “People are voting with their feet whether someone wants a claim to biopsy or not. It's only a matter of a generation.”
Recorded onsite in Washington DC, Scott Friedman, Jörn Schattenberg, Rachel Zayas and Roger Green discuss takeaways from the first three days at the 73rd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD). The group encapsulates the dynamic, vibrant energy of returning to this momentous event which welcomed back over 7,000 in-person attendees.
In this conversation, Rachel injects fascinating new considerations to the podcast through her lens from the microbiome. She begins by highlighting a poster presented by Curtis Gabriel. The study, titled Diabetic Persons with HIV and Hepatic Steatosis Have Reduced Intestinal Microbial Diversity, links intestinal dysbiosis and hepatic steatosis in patients with HIV. Rachel notes the topic to be compelling yet underexplored. Her curiosity questions, what does the normal microbiome look like initially and how does this change over time? Scott suggests society-wide changes in our food and use of antibiotics are important indices to investigate. Discussion digresses other related phenomena as antibiotics are not the only agent society has introduced to ecosystems.
Scott distills what he determined to be an eye-opening theme of the meeting in saying, “the Devil is in the details.” He describes himself as always looking to reduce complex topics to main, big picture themes. Contrarily, this meeting made clear to him how complex NAFL-D really is. He regards the complexities and differences in cell backgrounds, microbiota and treatment patterns as components of a longer-term challenge. Despite this challenge, he is confident the disease will yield to therapies incrementally and effectively.
NAFLD is noted to be a complex disease with a set of interrelated issues. Scott provides several examples of this, including Stephen Harrison’s presentation on a fatty acid synthase inhibitor (discussed in a later conversation). Jörn points out that a drug does not have to affect all the key targets to have an impact on the disease. This leads Rachel to ask in addition to what is driving disease, what are the protective mechanisms? Do they lie in epigenetics? Scott concurs and provides an example based on hyperlipidemia and the PCSK9 class. As this session winds down, Roger comments that we might not need to know exactly why an agent or therapeutic approach works to know that it does work. Instead, we can expect to solve the why as reverse engineers.
This week attendees from around the world convened at the 73rd Annual AASLD Liver Meeting for a lively and momentous event in Washington DC. On the final morning, Stephen Harrison, Sven Francque, Jörn Schattenberg, Ian Rowe and Jeff McIntyre join Roger Green to discuss key takeaways.
Sven is first to expand on a presentation that struck notable interest. He chooses to highlight a presentation by Laurent Castera, which Mazen Noureddin anticipated in our preview coverage. This focuses on a prospective head-to-head comparison of the different non-invasive tests in a large cohort of T2D patients with NAFLD. The paper concluded that FASTTM and MAST scores outperformed MEFIB, FIB-4 and NFS for identifying fibrotic NASH in T2D patients with NAFLD. Stephen broadens Sven’s analysis by noting FibroScan-AST as a standout test that is generally available for multiple different applications. The group puts forth commentary on the cost effectiveness and accuracy of these tests within enriched populations. As this subject winds down, Ian points to the particular challenge of selecting patients for treatment. The reality, he says, is that it’s not a one size fits all approach.
The conversation transitions from diagnostics to the topic of drugs. Stephen walks through his presentation on efficacy and safety of Akero’s lead product candidate efruxifermin (EFX) in patients with clinically relevant NASH (F2-F3). The results point to EFX significantly improving liver histology, liver fat content and noninvasive markers of liver injury, fibrosis, and glucose and lipid metabolism in patients with F2/F3 fibrosis due to NASH. Stephen shares his optimism for this particular FGF-21 agonist while Sven agrees that “not all FGF 21’s are created equal.” The group explores the science behind the structure of the EFX compound before Roger recalls the question of where the right use for such a drug might exist. It’s been previously suggested on this podcast that an application might resolve in induction therapy. With this in mind, the group addresses the dynamics of what happens when disease is reset to a point where there is far less liver damage. Following, Roger introduces a brief assessment of Arun Sanyal’s presentation of topline results from a new analysis of the REGENERATE Trial.
The last major theme discussed revolves around the session on nomenclature. Jeff offers an objective account of how this subject reported before disclosing his disappointment in the prospect of a name change from the patient perspective. His concern lies in the potential for a change to be confirmed without appropriate feedback from the patient group. He also questions the timing of such a decision as the field closes in on a drug approval. The other panelists respond with their impressions and the consensus is that virtually nobody is in favor of a name change at this point in time if it stands in the way of progressing drugs and diagnostics.
The breadth, quality and novelty of this conversation reflects yet another exceptional and positive Liver Meeting, this time back in person. In lieu of the typical business report, Roger and Stephen conduct a special interview with Michael Corbin from Inventiva. The three discuss the work of this clinical-stage biopharmaceutical company and its relevance to Fatty Liver. Inventiva develops novel and differentiated oral small molecule therapies for patients suffering from diseases with significant unmet medical need. Surf on for the full feature.
In an insight-laden conversation recorded on site from Washington DC, Scott Friedman, Jörn Schattenberg, Rachel Zayas and Roger Green discuss takeaways from the first three days at the 73rd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD). The group encapsulates the dynamic, vibrant energy of returning to this momentous event in person:
Scott illustrates how progress in the field of Fatty Liver is more a journey of many milestones and not an all-in-one blockbuster conclusion.
Rachel injects fascinating new considerations to the podcast through her lens from the microbiome.
Jörn investigates the mechanistic components of compelling research stories emerging from this conference.
Stay tuned and surf on for the full coverage!
Manal Abdelmalek, Jörn Schattenberg and Ian Rowe join Stephen Harrison, Louise Campbell and Roger Green to recap NAFLD and NASH-related insights from TLMdX 2021, the AASLD annual liver meeting. This conversation focuses on crafting the most robust efficient pathway to shift the gold standard of drug development from semi-quantitative biopsy reads to intelligent use on non-invasive techniques.
Opinions diverge about everything from how easy it will be to replace biopsy to exactly what that pathway might look like. What is clear is that everyone in this discussion believes with a hot passion that biopsy is a critical impediment to getting drugs approved.
In a follow-up preview, Jörn Schattenberg, Louise Campbell, Mazen Noureddin, Ian Rowe and patient advocate Jeff McIntyre join Roger Green to discuss key presentations and posters of interest at the 73rd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD). On November 4th-8th in Washington DC, as many as 10,000 attendees will convene in an effort to advance and disseminate the science and practice of hepatology, and to promote liver health and quality patient care.
Ian leads with a reference to the preceding conversation on a poster that describes ways to utilize AI or other analytics of items in basic medical charts to predict NAFLD. He endorses the idea of putting as few barriers in the way of primary care as possible, speaking to FIB-4 as an excellent front-line tool for primary care initial triage. He discusses the value of BMI as being a superior predictor to more complex measures and recalls Stephen Harrison’s KISS principle as a goal. He notes that patients will be referred for obesity if their BMIs are high enough regardless of whether they exhibit proven NAFLD. Next, he describes the process the NHS used in the UK to select reimbursed programs. He suggests that while there are questions regarding diet and rate of weight loss relevant to the Fatty Liver community, patients with obesity should be treated for weight loss as a simple solution. From here the other panelists provide final thoughts and closing comments on what the field can do to drive NAFLD care and screening to primary care providers. Surf on for their response, and stay tuned for more 2022 AASLD coverage.
In a follow-up preview, Jörn Schattenberg, Louise Campbell, Mazen Noureddin, Ian Rowe and patient advocate Jeff McIntyre join Roger Green to discuss key presentations and posters of interest at the 73rd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD). On November 4th-8th in Washington DC, as many as 10,000 attendees will convene in an effort to advance and disseminate the science and practice of hepatology, and to promote liver health and quality patient care.
Continuing from the previous conversation, Roger starts by questioning what the right long-term commercial model for remote patient wellness management companies might be. He recalls the early successes of Jenny Craig or Nutrisystem, achieved from selling food and Weight Watchers by branding other companies’ white-or black-labled food products. Is there the potential for these companies to marry strong coaching to services offering high-quality, pre-cooked foods for an integrated offering? Jeff agrees and refers to his own experience working with groups on medically-tailored meals. He briefly notes the push he sees to get these meals paid for by Medicare or private insurers. Louise mentions that the kinds of programs described exist at Safari parks as part of a full-wellness program for the animals. From a different perspective, she notes the importance of patient volition in program success and that volitional assessments are not included in trial design. The app Tawazun Health recently launched adds a volitional element.
Roger returns to a comment made in the first preview episode. He had talked about finding improved primary care screening tools that might serve a dual purpose by also educating front-line providers how NAFLD often sits at the core of the galaxy of metabolic diseases. Two abstracts for posters are described that address this issue. The first of which is a meta-analysis of 121,975 patients. This study looked at significance of the odds and hazard ratios of the TyG index, computed based on triglyceride and glucose levels. It also investigated the ability over time for that ratio to predict disease. All results were highly significant and clinically meaningful. The second poster is titled Performance of Artificial Intelligence Enabled Electrocardiogram and the Prediction of Fatty Liver Disease. This paper showed that an AI analysis of ECG results based on a convolutional neural network produced an area under the curve far superior to FIB-4. It also showed to be superior or equal to BMI and simple metabolic parameters. Roger’s general point: using these metrics can improve on FIB-4 while, at the same time, focusing on the links between NAFLD and other metabolic diseases. As the conversation winds down, Mazen and Jörn agree with a few additional comments.
In a follow-up preview, Jörn Schattenberg, Louise Campbell, Mazen Noureddin, Ian Rowe and patient advocate Jeff McIntyre join Roger Green to discuss key presentations and posters of interest at the 73rd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD). On November 4th-8th in Washington DC, as many as 10,000 attendees will convene in an effort to advance and disseminate the science and practice of hepatology, and to promote liver health and quality patient care.
Jörn starts this conversation by noting his anticipation for Parallel 12: NASH therapeutics and OMICs. Specifically, he points to an abstract titled Novel Mobile Health Delivered Lifestyle Intervention Program (Noom Health Weight) in Patients with NASH: a randomized controlled proof of concept study. This is a small trial in patients with NASH and obesity. The study sought to measure weight loss alongside weekly engagement with the Noom Healthy Weight app. 70% of patients met the engagement goal and lost an average of 5.3 kg over 16 weeks. Patients undergoing a more typical lifestyle management lost an average of 1 kg. Jeff joins to highlight the potential of a remote technology to generate 70% weekly engagement. He also finds this data promising in terms of providing a program that patients can use to measure health and manage fatty liver disease. By contrast, Jeff discusses recent conversations with a patient recently diagnosed with NAFLD who was not maintaining successful self-management due to obscurity of direction. Roger cautions that while this trial reported “no adverse event,” it consisted of a small sample size and short study duration. He also raises questions around the commercial model buttressing this study: who is paying and for how long can they maintain motivation? He envisions a more viable approach will be supported by commercial payers, who in return are investing in health care data. Given this may take some time to play out, Roger casts a third suggestion: FDA-approved digital therapeutic apps. He predicts this to be fertile grounds for patient empowerment over the next few years.
As this session winds down, Jeff responds to several of Roger’s comments and notes the turbulent impact of a pandemic on participation in wellness apps. This topic extends into the next conversation.
In a follow-up preview, Jörn Schattenberg, Louise Campbell, Mazen Noureddin, Ian Rowe and patient advocate Jeff McIntyre join Roger Green to discuss key presentations and posters of interest at the 73rd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD). On November 4th-8th in Washington DC, as many as 10,000 attendees will convene in an effort to advance and disseminate the science and practice of hepatology, and to promote liver health and quality patient care.
Louise leads this conversation with commentary carrying over from last week’s discussion on FibroScan as an essential test. Her hope remains that FibroScan be utilized in the early screening process, noting that many patients with poor liver health are still captured much too late in the process. She agrees with the consensus that, while imperfect, FIB-4 currently has the potential to improve patient capture rates. Mazen follows up with a comment on the nature of PPV being highly subjective to both test accuracy and patient population.
Ian suggests that some of the preceding conversation anchors performance of these tests to biopsy. Interested in moving beyond biopsy, he points out presentations which compare outcomes of patients according to either biopsy or associated noninvasive tests. The first paper he notes is titled Prognostic Value of Non-Invasive Tests in Patients with NAFLD. This study looks at outcomes for 1,700 patients with various non-invasive tests and demonstrates the value of each in predicting outcomes. Ian explains the conclusion is that NITs should be accepted as surrogate tests for clinical trials. He then looks at a presentation by Samer Gawrieh which correlates VCTE values with progression to cirrhosis and clinical events. He believes this to be the direction in which the field should move.
Mazen agrees with the idea that as data accumulates around NITs, we can better understand how longitudinal changes impact outcomes. He then briefly describes other presentations and posters at this meeting that address similar topics. His final comments describe the FDA’s interest in NITs: how do we give meaning to improvements in the efficacy of NITS and how do these improvements translate into better outcomes.
In a follow-up preview, Jörn Schattenberg, Louise Campbell, Mazen Noureddin, Ian Rowe and patient advocate Jeff McIntyre join Roger Green to discuss key presentations and posters of interest at the 73rd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD). On November 4th-8th in Washington DC, as many as 10,000 attendees will convene in an effort to advance and disseminate the science and practice of hepatology, and to promote liver health and quality patient care.
This conversation focuses on a presentation by Laurent Castera from Parallel Session 33 on Monday afternoon. The abstract looks to validate and compare head-to-head the FASTTM, MAST, and MEFIB scores as well as FIB-4 and NAFLD fibrosis score in a large cohort of T2D patients with NAFLD. Mazen points out that while the paper compares the various tests, the key is to ask which test is best for each specific purpose. In general, these results show that MAST and FAST perform better than the other three tests in terms of area under curve. Results also indicate that MAST has an indeterminate range of around 20%, as compared to 44% for FAST and MEFIB. The latter result suggests to Mazen that the researcher will need fewer biopsies to classify patients using MAST and MAST should score better on true classifications. Roger refers to last week’s discussion around which test to use at different points in the patient screening process. Mazen notes that while he has concerns with FIB-4, it remains as one of the best primary test options today. He repeats Stephen Harrison’s question from last week on whether we should start primary screening with FibroScan instead of FIB-4.
As the session ends, Jörn suggests that the discussion on best clinical use will continue. He notes that the goal of this paper is to contribute to discussion around the value of each test, ‘the true task of academia.’
In a follow-up preview, Jörn Schattenberg, Louise Campbell, Mazen Noureddin, Ian Rowe and patient advocate Jeff McIntyre join Roger Green to discuss key presentations and posters of interest at the 73rd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD). On November 4th-8th in Washington DC, as many as 10,000 attendees will convene in an effort to advance and disseminate the science and practice of hepatology, and to promote liver health and quality patient care.
Mazen begins by highlighting a presentation by Laurent Castera which covers an abstract the two collaborated on. The paper looks to validate and compare head-to-head the FASTTM, MAST, and MEFIB scores as well as FIB-4 and NAFLD fibrosis score in a large cohort of T2D patients with NAFLD. Roger notes last week’s discussion on use of FIB-4 as a primary screening tool, commending its performance in NPV but not PPV. He suggests this study offers a way forward for an enriched population who would benefit from a test offering high PPV and a narrow indeterminate zone. Jörn and Louise respond with their thoughts on FIB-4 as a cheap, accessible tool for primary care. Their analysis aligns with a conclusion from last week’s preview: FIB-4 is not a tool for the specialist’s office but, instead for primary care practices conducting first-line screening.
Ian suggests some of the preceding conversation anchors performance of these tests to biopsy. Interested in moving beyond biopsy, he points out presentations which compare outcomes of patients according to either biopsy or associated noninvasive tests. The first paper investigates whether screening for advanced fibrosis in the community can identify the subgroup of people with NAFLD at higher risk for development of liver-related complications. The study aimed to determine the prognostic value of baseline noninvasive fibrosis tests for predicting liver-related outcomes and mortality in patients with NAFLD from T2D clinics or primary care. Ian then looks at a presentation by Samer Gawrieh which follows the aforementioned abstract with data on progression. Mazen agrees with the idea that as data accumulates around NITs, we can better understand how longitudinal changes impact outcomes.
Jörn highlights his anticipation for Parallel 12: NASH therapeutics and OMICs. He specifically points to a presentation by Jonathan Stine on answering an unmet need to develop effective lifestyle intervention programs. This randomized proof of concept trial evaluates the feasibility, acceptability and safety of a novel commercially available mobile health app. This topic immediately resonates with Jeff, who is encouraged by two elements: the development of remote personalized technologies and the resulting patient empowerment. Roger raises questions around the commercial model buttressing this study: who is paying and for how long can they maintain motivation? He envisions a more viable approach will be supported by commercial payers, who in return are investing in health care data. Given this may take some time to play out, Roger casts a third suggestion: FDA-approved digital therapeutic apps. He predicts this to be fertile grounds for patient empowerment over the next few years. After some back and forth with Jeff, Roger shifts focus to his interest in posters on primary care screening and the metabolic-NAFLD link. Mazen shares his enthusiasm for the potential of machine learning to ensure accuracy in the use of NITs.
As time winds down, the panelists provide closing comments touching on a number of topics. It’s noted that this data-rich, insight-laden conference will host a dynamic inclusion of presentations on therapeutics, drug development and solutions deployed to market. Stay tuned for the upcoming live recorded coverage from Washington DC.
When AASLD announced that the 2021 event would be held as a purely virtual meeting, attendees and observers feared a loss of focus and the kind of amplifying energy that comes from being with colleagues. As this episode suggests, the breadth, quality and novelty of the meeting’s presentations generated exceptional positive energy even though colleagues could not meet in person throughout the event. In particular, this group noted the many ways in which the conference format and presentation implicitly challenges some older beliefs and perspectives about NAFLD, NASH and the people who live with these diseases.
Surf on for a conversation focused largely on determining key takeaways from the 2021 meeting and predictions as to what would be the big stories in 2022.
The 73rd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) takes place on November 4th-8th in Washington DC. As many as 10,000 attendees will convene in an effort to advance and disseminate the science and practice of hepatology, and to promote liver health and quality patient care. Key Opinion Leaders Stephen Harrison, Jörn Schattenberg and patient advocate Jeff McIntyre join Roger Green to preview key presentations and posters of interest.
This conversation continues from the theme that NAFLD is not a disease of affluence. Roger notes data from Zobair Younossi which reveals extremely high rates of NAFLD in the Middle East and North Africa region - a region recognized for the wealth of its residents. Jeff connects this prevalence to growth in easy-to-access, overprocessed, low nutrition foods. “If anything, it is not a question of ease of access, but which foods are easy to access.” He is enthusiastic that with the possibility of earlier diagnosis in identifying F2 patients, earlier intervention can follow.
Jörn suggests another issue that might help: NAFLD is a precursor to hepatic cell carcinoma (HCC). For many patients, HCC comes before progression to cirrhosis. Roger expands this observation, noting NAFLD to be a predictor of a range of non-liver cancers in addition. Stephen expresses the need to draw attention to treating Fatty Liver, which is the “canary in the metabolic dysregulation coal mine.” He says that if all we do is raise awareness of the need to treat, we have accomplished quite a lot.
Roger briefly references posters that take innovative looks at how to create inexpensive, widely available screening through tests and/or analysis of medical records. At the end, he invites everyone back next week to discuss more of the presentations and this data-rich, insight-laden conference. The closing question explores one important thought about the meeting each panelist wants to raise before the next preview discussion.
The 73rd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) takes place on November 4th-8th in Washington DC. As many as 10,000 attendees will convene in an effort to advance and disseminate the science and practice of hepatology, and to promote liver health and quality patient care. Key Opinion Leaders Stephen Harrison, Jörn Schattenberg and patient advocate Jeff McIntyre join Roger Green to preview key presentations and posters of interest.
This conversation starts with Stephen’s comments on the presentation covering fibrosis progression rates for diabetic vs. non-diabetic patients with biopsy-proven NAFLD. Stephen says it highlights important elements of the diabetes population, who are known to have significantly higher rates of NASH and fibrosis. This study demonstrates faster progression rates for this population. He makes two notes of interest: First, this is a relatively young population. Second, while the mean BMI is clearly obese at 34, it is lower than many patients seen by hepatologists in clinic. He suggests that older patients with progressed obesity might demonstrate more dramatic results. In closing, he wonders whether duration or severity of diabetes impacts the speed of fibrosis progression.
Focus shifts to papers and presentations identified by Jeff McIntyre. He notes two items, the first of which is Donna Cryer’s Patient Keynote address titled, Liver Health Equity: Overcoming Stigma, Access and Policy Barriers. Jeff comments that stigma, access and policy barriers are themes that actually run through the entire agenda. He cites a range of issues that reflect on challenges facing health equity, but also overall patient care and support. For example, he mentions the broadened use of NITs. He also points specifically to a session called Liver and Queer, an introduction to the AASLD LGBTQ task force.
With Louise Campbell absent, Roger looks to Jörn for a response to challenges facing health equity. Jörn states, “NAFLD has inequality written all over it,” citing far reaching factors including food distribution, access to care and green spaces where people feel safe while exercising. He looks forward to Donna discussing how to overcome these issues from a patient advocacy perspective.
Finally, Jeff and Jörn agree on two public perceptions that need to be addressed: NAFLD as a disease of affluence and food issues standing somewhat independent of health.
The 73rd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) takes place on November 4th-8th in Washington DC. As many as 10,000 attendees will convene in an effort to advance and disseminate the science and practice of hepatology, and to promote liver health and quality patient care. Key Opinion Leaders Stephen Harrison, Jörn Schattenberg and patient advocate Jeff McIntyre join Roger Green to preview key presentations and posters of interest.
The preceding conversation finished with Jörn discussing the proper use for FIB-4 (in referral pathways) and the improper use (in specialty practices and clinics). This conversation picks up with Jörn listing tests he prefers in his clinic: MRE and FAST. Stephen notes that many guidelines recommend FIB-4 followed by FAST. He asks, why not start with both and improve our ability to identify patients who need therapy? Roger responds by mentioning a poster from Mayo Clinic (#2309, Performance of AGA Clinical Care Pathway for the Risk Stratification of Patients with NAFLD in the US population). The poster suggests defining the AGA guidelines so that only patients with Type 2 diabetes and FIB-4 >1.3 would reduce the number of scans by almost 10 million, or 70% of demand. This would not significantly affect how many patients are missed. The group agrees this is a good approach in specialty practices, but probably not easy to implement or cost-effective in primary care.
Jörn shifts focus to Daniel Huang’s presentation at Sunday’s Presidential Plenary session. The presentation compares fibrosis progression rates for diabetic vs. non-diabetic patients with biopsy-proven NAFLD. He notes two key findings of interest: First, while it has always been assumed that fibrosis progresses one level in seven years, the number for patients with diabetes may be closer to one level every six years. Second, the cumulative progression over the entire populations in a 12-year period was 93% for patients with diabetes and 76% for patients without diabetes. Jörn notes this to be a significant difference in patient numbers, highlighting an urgent need for treatment in the diabetic population.
The 73rd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) takes place on November 4th-8th in Washington DC. As many as 10,000 attendees will convene in an effort to advance and disseminate the science and practice of hepatology, and to promote liver health and quality patient care. Key Opinion Leaders Stephen Harrison, Jörn Schattenberg and patient advocate Jeff McIntyre join Roger Green to preview key presentations and posters of interest.
This conversation focuses on a presentation by Rohit Loomba that will review results from MAESTRO-NASH, a 2,000-patient Phase 3 trial. Stephen highlights that this analysis demonstrated FIB-4 with a cutoff of 1.3 failed to identify 57% of F2 patients, 40% of F3 and 26% of F4. To Stephen, this implies that if we rely solely on FIB-4, “we’re probably leaving behind a lot of patients that should be treated.” He suggests adding VCTE to FIB-4 to improve precision in screening these patients. As the session ends, Jörn shares his impressions and agrees with Stephen that FIB-4 is inappropriate for specialty clinics. He notes that the primary anticipated use is to screen patients in referral pathways where the number of patients with clinical fibrosis is far lower.
The 73rd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) takes place on November 4th-8th in Washington DC. As many as 10,000 attendees will convene in an effort to advance and disseminate the science and practice of hepatology, and to promote liver health and quality patient care. In this preview, Key Opinion Leaders Stephen Harrison, Jörn Schattenberg and patient advocate Jeff McIntyre join Roger Green to discuss key presentations and posters of interest.
Earlier this month, Stephen and Jörn joined Roger, Louise Campbell and Mazen Noureddin to review a string of recent press releases on NASH drug development. Many of these are AASLD late-breakers. Today's podcast covers presentations and posters not discussed previously.
Stephen begins by mentioning an analysis Rohit Loomba will present from MAESTRO-NASH results, a 2,000-patient Phase 3 trial. This analysis demonstrated that FIB-4 with a cutoff of 1.3 failed to identify 57% of F2 patients, 40% of F3 and 26% of F4. To Stephen, this says if we rely solely on FIB-4, “we’re probably leaving behind a lot of patients that should be treated.” He suggests adding VCTE to FIB-4 to improve precision in screening these patients.
Jörn and Roger have a common reaction: FIB-4 is not a tool for the specialist's office but, instead for primary care practices conducting first-line screening. Jörn states that the guideline referrals for FIB-4 use apply specifically to primary care and that in his clinic, he would never evaluate a patient solely based on FIB-4. Roger comments about a large number of papers at the conference seeking to improve efficiency and reduce cost of front-line screening, not to add literally millions of VCTE tests per year to primary care schedules and budgets. Jörn closes the discussion by saying that the common message to the field today is that FIB-4 is an important primary care tool, but it is far from perfect and we should seek better options over time.
Jörn focuses on Dr. Daniel Huang’s presentation at Sunday’s Presidential Plenary session comparing fibrosis progression rates for diabetic vs. non-diabetic patients with biopsy-proven NAFLD. He notes that while conventional wisdom is that NASH progresses by one stage of fibrosis every seven years, the rate for diabetic patients in this study is reported to be one stage every six years. This leads to a broader discussion about screening and treatment for patients with diabetes, where the emerging consensus is to assume NAFLD and screen for NASH and fibrosis.
Jeff McIntyre focuses on patient issues by discussing Donna Cryer’s “Health Equity” talk on Saturday morning. Jeff suggests while we all think of health equity in context of stigma, access and policy barriers, these are broader than simple equity issues. “Access,” he notes, can refer to how adoption of NITs in clinical trial programs will make trials practical for a larger number of patients. “Stigma” refers not only to the stigma of liver disease, but also to whether stigmatized groups such as the obese or people living with HIV get care sensitive to their needs. To that end, he points specifically to a session at 10:30a Saturday morning called “Liver and Queer,” an introduction to the AASLD LGBTQ task force. This bridges into discussions about obesity and its global implications, one of which is that Fatty Liver leads to HCC and other cancers… and from there to ways to draw attention to the need to treat Fatty Liver, which Stephen describes as the “canary in the metabolic dysregulation coal mine.”
As time winds down, Roger briefly references a couple of posters that take innovative looks at how to create inexpensive, widely available screening through tests and/or analysis of medical records. He invites everyone back next week to discuss some more of the presentations and this data-rich, insight-laden conference.
One of the most intriguing presentations at the inaugural Innovations in NAFLD Care 2022 conference (INCBCN) came from physician, author and entrepreneur Dr. Marcus Ranney. In this conversation, Roger Green interviews Marcus on his experiences unique vision and the future of #biohacking.
In this conversation From the Vault, Marcus discusses his own “journey of figuring out…how to augment [his] own health.” He describes his personal history and career, how he came to write the best-selling book “At the Human Edge,” to begin his Human Edge consultancy and to begin developing the #biohacking app Mito. Along the way, we learn about his long-standing passion for mitochondria and the ways experiencing long-haul COVID-19 has affected his health and perspective. From a market perspective, he discusses the rapid growth of technologies designed to collect and share information about the individual’s metabolism.
From the platform of understanding Human Edge and Mito, the dialogue veers into broader social issues. Roger discusses how the conference presented and amplified four very different views of power and control in managing individuals’ health. Marcus shares his view that if we are to address social developmental needs and goals necessary to advance health, data — at all levels — will be key to formulating, evaluating and improving strategies and programs. These ideas do not sound radical in their one-sentence summaries, but the discussion is richer, farther-reaching and more powerful than the summaries themselves suggest.
One critical success factor for putting a dent in Fatty Liver disease – one we do not discuss very often on the podcast – is patient empowerment. In this conversation, Roger Green and Louise Campbell are joined by patient advocates Michael Betel, Wayne Eskridge and Robert Mitchell-Thain to discuss the use of FIB-4 as a front-line tool for primary care triage.
Roger starts by noting FIB-4 as cheap and relies on a small number of widely-used tests. At different levels, FIB-4 is prognostic not only for major adverse liver outcomes and mortality but also at its indeterminate level for cardiovascular and overall mortality. He connects the most recent Rising Tide episode, where it’s mentioned that the US may be the only country to include AST so widely in standard testing. It's asked in that episode whether this is an issue advocates can adopt and use to advance disease awareness and screening. Wayne endorses the idea and Robert expresses some concern about FIB-4. Robert does acknowledge that Fatty Liver Alliance’s new charity status positions it as an excellent organization to make the major change.
The final question asks each advocate what change they can make in their country in the next 12 months that might extend beyond the country’s borders. Surf on to hear their answers.
Patient empowerment can be an overlooked, yet critical success factor for putting a dent in Fatty Liver disease. In this conversation, the panelists investigate the economics of pathway design while identifying challenges and opportunities for effective solutions.
The preceding dialogue has suggested that the guideline processes are too focused on opportunities for private sector product developers to make money. Roger Green challenges this idea by identifying FIB-4 as the first stage test across all guidelines and pathways. He notes FIB-4 is an inexpensive test that will not profit manufacturers. Louise Campbell agrees before shifting focus to challenges obstructing effective pathway design. She notes a disconnect between systems and the lack of integrating agents and organizations to implement multi-specialty clinical care pathways.
Robert Mitchell-Thain responds with two key points: NAFL-D is not merely a liver disease and any solution must play on the potential for partnerships between organizations and professionals. He asks the group to envision a world where patients are identified earlier in disease and supported with such strong information and tools that many may never need medication. Louise endorses this viewpoint before highlighting a specific shortcoming in UK health systems. She points out that focus is oriented toward high cost individuals, downstream in disease progression, who cost 3.6B pounds per year. Such a strategy fails to provide sufficient support to earlier stage patients who will cost 19B pounds collectively.
Patient empowerment can be an overlooked, yet critical success factor for putting a dent in Fatty Liver disease. This conversation details the involvement of three patient advocates in developing clinical care pathways and guidelines.
Louise Campbell opens with a suggestion that companies focus mostly on purchasers of medication. This rarely includes patients, who are more often considered end users in advanced economies. Emphasizing the resourcefulness of patient advocates, she expresses gratification that our panelists feel better listened to in the development processes today than in the past. She shares her perspective that liver disease needs to be part of every conversation across metabolic health. Louise notes approvingly of a recently attended primary care meeting where liver played a significant role. Michael Betel adds that AASLD now hosts significant patient contributions - a new and major improvement.
Roger shifts to focus on how closely the advocates are involved in developing clinical care pathways and guidelines. He refers to recurring conversations on the podcast with physician advocates. Those considering the totality of disease are looking for ways to simplify and structure pathways and guidelines to best benefit the whole system. Robert Mitchell-Thain builds on the idea that it is important to create and adopt patient-friendly guidelines. He suggests that it is equally important to develop tools which allow patients to understand and utilize these guidelines. Michael mentions his contributions to the Canadian guidelines being developed. Wayne Eskridge expresses concern that too much focus of the guidelines is on drugs and not enough on self-care from earlier in the disease cascade.
One critical success factor for putting a dent in Fatty Liver disease – one we do not discuss very often on the podcast – is patient empowerment. This conversation begins by carrying over thoughts on the future of digital therapeutics as a Pharma-supported patient wellness tool with advocates Michael Betel, Wayne Eskridge and Robert Mitchell-Thain.
Robert connects the idea with a comprehensive patient support tool the PBC Foundation has built for patients. Delivered as an app, this tool hosts features on disease information, self-care and ways the Foundation can provide service to patients. Robert offers a detailed glimpse into each of these functions. This prompts Wayne to ask a series of practical questions around the delivery of similar hypothetical tools in the Fatty Liver space: How will they be approved, prescribed and paid for? Robert returns to discuss the PBC Foundation free app as an example. Of the many benefits served, Robert highlights the app’s contribution toward surveying the patient population, their journey and improving experience through patient feedback. The ability to generate patient-centric data is invaluable for presentations to medical societies and whomever else can utilize it to improve self-care tools and experiences. Such efforts are pivotal in defense to what Robert terms the “psychological warfare” put forth by major food manufacturers.
Roger then turns to Wayne and Michael, asking for something accomplished in the last year consistent with the charter of their organization. Wayne introduces a project called the Wellness League hosted by the Fatty Liver Foundation. This project is designed as an ecosystem for the nonprofit community to address the challenge of distributing information and promoting on-ground education. Michael celebrates the accomplishment of gaining Canadian charity status for the Fatty Liver Alliance.
One critical success factor for putting a dent in Fatty Liver disease – one we do not discuss very often on the podcast – is patient empowerment. In this conversation, Roger Green and Louise Campbell are joined by patient advocates Michael Betel, Wayne Eskridge and Robert Mitchell-Thain to discuss patients’ perspectives and the extent they are considered in the clinical trial design process.
Louise leads with the question: When planning drug trials, to what degree do BioPharma companies focus on the eventual needs of the patient? Each advocate expresses significantly different perspectives. Robert starts by answering a different question: Do companies “get it?” He states that of the myriad of views held by industry partners, his focus remains on harnessing the efforts of those championing patient-centricity.
Michael refers to his unique experience of having worked both for commercial pharma and non-profit organizations. He believes that while the patient journey matters tremendously, it’s not considered in the earliest stages of drug development. Wayne’s answer echoes this sentiment while emphasizing that interest in patient needs is driven out of marketing, not clinical development. He does note patient sensitivity has improved in recent years.
Roger follows up, spurring investigation into the distinction between driving perpetual drug use versus creating accessible, valuable therapeutic solutions. Robert carefully discloses his discomfort with industry and NAFLD, but not NASH. He states that all three guests have improved their lived experiences with NAFLD without medical intervention. For Robert, these successes correlate with early interventional lifestyle changes, highlighting the importance of peer support. Michael returns to his idea that drug companies seek to remove barriers that limit access to treatment. Wayne expresses concern for the potential of conflicting motivators to pit social values against the accountabilities a company holds for making market systems work.
The conversation finishes with a segue into the future of digital therapeutics as a Pharma-supported patient wellness tool.
One critical success factor for putting a dent in Fatty Liver disease – one we do not discuss very often on the podcast – is patient empowerment. In this episode, Roger Green and Louise Campbell are joined by patient advocates Michael Betel, Wayne Eskridge and Robert Mitchell-Thain to discuss patients’ perspectives and their contributions to improving healthy liver outcomes.
Louise opens conversation by asking whether trial designs incorporate patient perspective from the outset or as an adaptation. Robert suggests there are a myriad of views held by industry partners, but ultimately emphasizes the value of harnessing the efforts of those championing patient-centricity. Michael shares his unique experience of having worked both for commercial pharma and non-profit organizations. He believes companies seek to remove barriers that limit access to treatment. Wayne notes the recent trend of industry including more patient input into development processes.
Roger spurs deeper investigation into the distinction between marketing perpetual treatment cycles and creating accessibility in receiving life-changing therapies. Robert carefully discloses his discomfort with industry and NAFLD, but not NASH. All three guests have improved their lived experiences with NAFLD without medical intervention. Robert correlates these successes with early interventional lifestyle changes, highlighting the importance of peer support. Later on, he also acknowledges the importance of trusted partnerships between clinicians, academia and other support organizations. Michael returns to his idea that drug companies seek measurable success in the treatment of patients, which does not equate to perpetual drug therapy. Wayne expresses concern for the potential of conflicting motivators to pit social values against the accountabilities a company holds for making market systems work.
Discussion shifts to panelists’ impressions on the phenomenon of digital therapeutics in the imminent future. Roger notes the economics and ability to make money in digital therapeutics will be different than in drugs, but the ability to support patients that way will be real. Robert connects the idea to his work with primary biliary cholangitis (PBC) and a health monitoring app the PBC Foundation developed for patients. Of the many benefits served, Robert notes the app’s contribution toward surveying the patient population, their journey and improving patient experience through patient feedback.
Roger turns to Wayne and Michael for something accomplished in the last year, consistent with the charter of their organization. Wayne introduces a project called the Wellness League hosted by the Fatty Liver Foundation. This project is designed as an ecosystem for the nonprofit community to address the challenge of distributing information and promoting on-ground education. Michael highlights the accomplishment of gaining Canadian charity status for the Fatty Liver Alliance.
Louise prompts further discussion on economic drivers of industry. The group investigates purchaser influence and patient advocacy represented at major meetings and events. Roger notes physician advocates considering the totality of disease are looking for ways to simplify and structure pathways and guidelines to best benefit the whole system. The guests outline their own contributions to these efforts from the position of patient advocate.
These are only a few insights from a far larger set that emerges during this discussion. Surf on for the full story.
This conversation From the Vault comes from Season 3 Episode 13.4, part of NASH Tsunami’s coverage of the first NICE meeting on FibroScan.
Season 3, Episode 13 looks at the NICE Draft Guidance Evaluating FibroScan use in Community and Primary Care settings. This conversation focuses on underlying tensions between a methodology designed to assess big-ticket spending on critical moments of disease and a population screening approach that centers on wellness care more than illness care.
The conversation starts with Roger Green noting an inherent tension between short-term health economic tests driving a decision not to compensate and longer-term healthcare priorities that rely on patients who cannot afford the test being able to take it. Ian Rowe describes this as a tension inherent in the UK system and therefore, not a “real issue.” In contrast, Jörn Schattenberg notes a significant structural issue in that, as Ian noted earlier, NICE relies on companies to provide the necessary data, but the costs of providing that data might be excessive for a small diagnostics company like Echosens, although not for a major drug company.
Jörn goes on to raise the issue of reimbursing wellness vs. illness; this is economics of illness analysis done for a process that enhances wellness. Louise Campbell suggests a parallel analysis of the cost of expensive HCC drugs like sorafenib that are highly costly but provide only 3-6 months added longevity. In the end, Roger Green asks one thing each participant would like to see vs. something they are confident they will see. Answers vary, but they suggest that the current system is not a particularly effective way to assess this kind of analysis and that, beyond that, this specific analysis might benefit from some different looks at data. In the end, Louise Campbell notes that the comment period ends on March 9 and invites as many people as possible to comment before then.
Amidst a shifting diagnostic pathway, the UK’s National Institute for Health and Care Excellence (NICE) reconsiders its position on vibration controlled transient elastography (VCTE) in the community. This final conversation centers around how to create and train on delivering meaningful test results to patients.
Roger Green begins with his note that in recent NASH Tsunami episodes, panelists have stated that their countries could not automate FIB-4 simply because liver enzyme tests are not standard in blood panels. This prompts Will Alazawi to suggest that a campaign similar to the one for people with diabetes on learning their HbA1c levels might go a long way toward driving between enzyme collection and FIB-4 use. Ian Rowe asks which number would be used for the liver. Louise answers that FibroScan results provide multiple metrics worth considering. She adds that while FibroScan offers substantial value, acquisition is too expensive to provide at scale. However, the less expensive tests are not adequately standardized or validated as predictive at an individual level.
The rest of the conversation centers on ways to consider and use tests before finishing with the closing question. Roger asks the panelists for one thing in this system worth improving. Ian calls for a clear pathway capable of efficient decision making. Louise hopes for NICE to take action on liver health to drive accessibility in primary care. Kate extends this sentiment to address inequities across communities. Will is looking for stronger signaling to answer patients' concerns: how bad is their Fatty Liver or fibrosis? Finally, Roger offers his US-centric response: if we can appropriately identify the liver’s place in multi-metabolic life, the field moves closer to acknowledgement as a big ticket item.
Amidst a shifting diagnostic pathway, the UK’s National Institute for Health and Care Excellence (NICE) reconsiders its position on vibration controlled transient elastography (VCTE) in the community. This conversation begins with Will Alazawi concluding his comments on the link between liver outcomes and socioeconomic status. The group then explores a range of factors contributing to inequity. Roger speaks to his marketing research experience which revealed physicians' frustration with an inability to drive patients toward sustaining lifestyle management goals. Will suggests that the challenges are not strictly socioeconomic, but concedes that a number of variables remain immeasurable at this point in time. For example, he poses a few yet to be answered questions: how much space do people have in their homes? Is there access to healthy food? What financial impediments exist? Louise and Kate comment on misunderstandings about alcohol consumption and liver health. All agree that an excess of “good quality” alcohol has the same deleterious effects on liver health as does an excess of cheap drink.
Discussion shifts back toward accessible pathways. Will and Louise suggest that the challenge lies in deploying hepatologist skills into the community more effectively. Kate questions who will administer the FibroScans in primary care, pointing to the shortage of nurses in the UK amongst other challenges. Ian thinks it may be impossible to implement solutions for every issue discussed in a scalable, cost effective way. He asserts that testing needs to be deliverable in a way that is meaningful to patients. Establishing a simple, communicable testing metric with accessible points of administration is key. This seems more difficult and expensive to achieve in the context of liver health than it has for identifying other successful metrics such as reading blood pressure.
Amidst a shifting diagnostic pathway, the UK’s National Institute for Health and Care Excellence (NICE) reconsiders its position on vibration controlled transient elastography (VCTE) in the community. Professor Ian Rowe and Dr Kathryn Jack discuss navigating a scarcity of relevant data for evaluating pathway development alongside Surfers Roger Green and Louise Campbell.
Roger prompts this conversation by asking the group whether there is a developed paradigm for how to adopt technology in places where the data is arriving in real time. He notes the difference between how this process is approached in open markets such as the US versus data-reliant markets similar to the UK. Ian describes a process used in oncology called “commissioning through evaluation,” where the NHS pays for medications while collecting the necessary real-world data to conduct evaluation. This point introduces political influence on decision making processes. Roger notes the resulting polarity in healthcare expenditure between the US and the UK.
Roger continues to spur discussion on the political pressures and metaphorical issues that shape the differences between cancer and liver disease management. Louise analyzes the linkages between poor liver health and non-hepatic cancers, insisting on a more robust consideration of the liver-to-cancer link. Ian mentions the ever increasing challenge for hepatology of treating more aggressively and effectively with NITs while simultaneously conducting research on the best way to do so. Kate suggests utilizing the nurses and allied health professionals that are willing to become involved in research and drive the required data forward.
At this point, Professor Will Alazawi joins the panel with an impressive debut. He returns to the idea that due to stigmas, liver and cancer do not occupy the same imagination in the general public. His ideas link socioeconomic strata with liver outcomes, suggesting marginalized patients are more likely to encounter complications of liver disease.
Amidst a shifting diagnostic pathway, the UK’s National Institute for Health and Care Excellence (NICE) reconsiders its position on vibration controlled transient elastography (VCTE) in the community. In this conversation, Roger Green and Louise Campbell are joined by Dr Kathryn Jack and Professor Ian Rowe to discuss the dynamic challenges of using FibroScan and other noninvasive tests (NITs) for best practice.
Louise begins by reflecting on the experience of the second public meeting around considering access to FibroScan for primary care. In describing the evaluation process, she notes a shift from analyzing costs per test to a broader focus around how these tests are positioned in the wider pathway. Ian agrees that FibroScan does not necessarily fit well within the traditional framework of NICE. Analytical challenges and out of system data obscure answers to critical questions such as what is the cost effectiveness of FibroScan in primary versus secondary care. Kate highlights the value of developing an early screening pathway. She shares her experience that when scanning patients, cirrhosis presents in those who have never been diagnosed with Fatty Liver. This is a pivotal opportunity to deliver a targeted intervention and support for the unwittingly cirrhotic population. For Kate, the decision to reimburse FibroScan community use is a “no-brainer.”
Ian challenges the practicality behind the idea that every patient in primary care should receive FibroScan. “It's important to bear in mind what NICE was asked and then to try and understand how we use FibroScan as part of the wider pathways.” He suggests community non-invasive fibrosis screening, but not necessarily FibroScan.
Amidst a shifting diagnostic pathway, the UK’s National Institute for Health and Care Excellence (NICE) reconsiders its position on vibration controlled transient elastography (VCTE) in the community. In this episode, Roger Green and Louise Campbell are joined by Dr Kathryn Jack and Professors Ian Rowe and William Alazawi to discuss the dynamic challenges of using FibroScan and other noninvasive tests (NITs) for best practice.
Louise opens the conversation by reflecting on the second public meeting around considering access to FibroScan for primary care. She notes a shift from analyzing costs per test to a broader focus around how these tests are administered and to whom. The group agrees that FibroScan does not necessarily fit well within the traditional framework of NICE. Analytical challenges and out of system data obscure answers to critical questions such as what is the cost effectiveness of FibroScan in primary versus secondary care.
Kate highlights the value of developing an early screening pathway. She notes that when scanning patients, cirrhosis presents in those who have never been diagnosed with Fatty Liver. This is a pivotal opportunity to deliver a targeted intervention and support for the unwittingly cirrhotic population.
Ian challenges the practicality behind the idea that every patient in primary care should receive FibroScan. He instead suggests non-invasive fibrosis testing in selected patients in the community. “It's important to bear in mind what NICE was asked and then to try and understand how we use FibroScan as part of the wider pathways.” Roger notes the difference between how this process is approached in the US versus the UK. He asks the group whether there is a developed paradigm for how to adopt technology in places where the data is arriving in real time. Ian describes ways the NHS can manage uncertainty and evidence for emerging technologies, citing an example from the cancer space. The conversation shifts toward how the liver can be politicized to arrive at a quicker, better decision.
Midway through the episode, Will makes his debut after being locked out of the recording session due to technical difficulties. In true breakthrough fashion, he introduces spiky ideas linking socioeconomic strata with liver outcomes. His thought: the more marginalized the patient, the more likely they are to encounter complications of liver disease. The group then proposes a range of factors contributing to inequity.
Kate steers discussion back to questions around administration of FibroScan and the challenges that oppose nurses and other healthcare professionals. Ian expands these questions and challenges in the context of delivering clear messaging. Settling on a simple, communicable metric may be more difficult and expensive for liver testing than other more recognized health indicators such as reading blood pressure.
At the bottom of the hour, Roger asks the panelists for one thing in this system worth improving. Ian calls for a clear pathway capable of efficient decision making. Louise hopes for NICE to take action on liver health to drive accessibility in primary care. Kate extends this sentiment to address inequities across communities. Will is looking for stronger signaling to answer patients' concerns: how bad is their Fatty Liver or fibrosis? Finally, Roger offers his US-centric response: if we can appropriately identify the liver’s place in multi-metabolic life, the field moves closer to acknowledgement as a big ticket item.
In Season 3, Episode 6, Roger Green assembles audio clips from Surfing the NASH Tsunami’s coverage of NASH-TAG 2022 to reveal an evolving view of the role combination therapies will play in the treatment and management of NASH patients. Discussion about “combination therapies” typically focuses on the idea of multiple agents prescribed concurrently to address a medical condition when monotherapy will not achieve desired goals. At NASH-TAG 2022, the concept of combination therapies took some interesting directions:
- Longitudinal drug combinations — initial intervention designed to cause a fast reversal of fibrosis or defatting of the liver, followed by a longer-term therapy (mono or combination, but not with the first-round agent) designed to provide longer-term, more complete metabolic benefits in a regimen that is safer, more tolerable, less expensive, or some combination of these.
- Longitudinal diagnostics — an early, inexpensive “rule out” test like FIB-4, followed by a liquid or machine-based test that provides more accurate disease staging.
- Logical combinations — so far, most drug combination trials have resulted from a manufacturer trying to resuscitate a developmental agent that missed endpoints in monotherapy trials. It would be more logical to design combinations based on complementary modes of action.
This episode explores these and other combination therapy issues using quotes from the NASH-TAG 2022 coverage and Roger’s commentary.
A recent string of press releases presaged some of the most exciting, promising data of the last decade in NASH drug development. This conversation explores the single unsuccessful trial result accompanying the spate of positive reports. Intercept’s REVERSE study focuses on evaluating the safety and efficacy of obeticholic acid (OCA) in patients with compensated cirrhosis. Stephen Harrison outlines the Phase 3 results which, ultimately, did not meet its primary endpoint. Stephen notes the analysis of the F3 REGENERATE trial continues and data from REVERSE may provide support for the REGENERATE safety story.
Louise Campbell takes optimistic interest in this study. She notes, given a cirrhotic population, an F1 improvement may be a difficult, if not unrealistic endpoint. There is value in stabilizing disease. She suggests a focus on improving outcomes and quality of life and halting progression in this most at risk population.
Mazen Noureddin suggests this drug be reserved for combination therapy. Provided the positive data in the preceding press releases, the bar is now much higher. Roger Green adds that ultimately, the results are not statistically significant for this trial.
Jörn Schattenberg is hopeful to glean learning beyond negative results. This is the largest cirrhosis study to date and it remains a challenge worthwhile to regress cirrhosis in compensated patients.
The conversation concludes differently than any other previous Surfing the NASH Tsunami episode. Surf on to discover more.
A recent string of press releases presaged some of the most exciting, promising data of the last decade in NASH drug development. In this conversation, the panel continues exploring oral drugs (specifically PXL-065) before reviewing positive interim data from the Phase 2b EMMPACT study by Axcella.
Roger Green notes that introducing multiple modes of action to the market will create the energy and investment to drive a dynamic explosion of education and exploration in Fatty Liver diseases. Stephen Harrison adds final thoughts on why PXL-065 may be a good choice in combination and/or long-term maintenance therapy. The discussion shifts to Axcella’s EMMPACT study, an ongoing global Phase 2b randomized, double-blind, placebo-controlled, dose ranging study to evaluate the safety, tolerability, and efficacy of AXA1125 for the treatment of NASH. The dose form comes in a unique liquid comparable to Tang drink mix. Stephen elucidates on the science behind using multi-targeted endogenous metabolic modulator (EMM) compositions. He presents the pre-planned interim analysis which offers promising findings regarding the effects of AXA1125 administration on selected outcome measures after 12- and 24-weeks of treatment. As the conversation ends, he contextualizes the results and comments on the broad activity of this drug in addition to its well-tolerated profile and safety.
A recent string of press releases presaged some of the most exciting, promising data of the last decade in NASH drug development. In this conversation, Stephen Harrison continues his review of Phase 2B results from Akero’s HARMONY Trial before introducing more positive Phase 2B results from a study by Poxel. Mazen Noureddin, Jörn Schattenberg, Louise Campbell and Roger Green share impressions.
Mazen asked whether the future must rely on combination therapies. The question leads Roger back to a comment Akero Chief Development Officer, Kitty Yale, made in a January 2021 podcast. She stated that Akero believes the future of NASH therapy might not hinge on combination therapies. Stephen suggests it prudent to continue following these results as it might be premature to discuss how this drug will be applied. The uncertainty stems from questions around the drug’s modes of action and delivery, potential for tolerability issues or possible reduction of effect over time. Roger asks whether this drug, like BMS’s pegbelfermin, might wear off over time. Stephen suggests that differences in the chemical structure of these two FGF-21 agents points that EFX might not do so. He explains how a drug like EFX could serve as induction therapy followed by a lower cost, better tolerated oral agent.
The conversation shifts to the next set of data produced by Poxel. The DESTINY-1 study reports positive histology results for PXL065, a novel, proprietary deuterium-stabilized R-stereoisomer of pioglitazone. Stephen elucidates on the science of this drug and the mechanics of deuterium as a stabilizer. The study design consists of 117 subjects across four cohorts: three different doses versus placebo. The trial met its primary efficacy endpoint for liver fat content reduction at 36 weeks for all doses. Louise emphasizes the positives associated with delivering an oral mechanism.
A recent string of press releases presaged some of the most exciting, promising data of the last decade in NASH drug development. In this conversation, Principal Investigator Stephen Harrison reviews Phase 2b results from Akero’s HARMONY Trial. Special guest Mazen Noureddin joins Jörn Schattenberg, Louise Campbell and Roger Green to share impressions.
This conversation starts with Stephen returning to his discussion of Altimmune’s dual GLP-1/glucagon agonist, pemvidutide. He comments that stock analysts appear to have punished Altimmune because pemvidutide did not demonstrate greater weight loss. He considers this an inaccurate read. He notes that the 12 week weight loss results of pemvidutide are comparable with 24 weeks with efruxifermin (EFX) in the extremely successful HARMONY Trial. Stephen then segues to detail HARMONY, a 24-week study evaluating the efficacy and safety of the FGF-21 agonist EFX in patients with clinically relevant NASH (F2-F3). The topline results:
- The study met its primary endpoint for both the 50mg and 28mg EFX dose groups.
- Respectively, 41% and 39% of EFX-treated patients experienced at least a one-stage improvement in liver fibrosis with no worsening of NASH by week 24 (compared with 20% for the placebo arm).
Stephen notes the presence of key secondary endpoints and important demographics of the patients. He also describes the program for histological analysis and goes on to highlight some extremely positive - perhaps eye-opening - results. Mazen and Jörn react by describing these two results as a Wow! episode. Louise adds comments on the potential for the NIT analysis to speed the transition beyond the biopsy.
A recent string of press releases presaged some of the most exciting, promising data of the last decade in NASH drug development. In this conversation, Principal Investigator Stephen Harrison reviews the top-line results of Altimmune’s 12 week Phase 1B study of pemvidutide, a GLP-1/glucagon dual receptor agonist.
Stephen describes the effects of pemvidutide on the liver’s fat creation and processing. “It's like taking a drug that both induces weight loss and increases exercise without actually having to diet or get out and exercise. So just think of this drug physiologically working in that particular manner.”
He goes on to outline the study design, patient qualification and restrictions, and an attention-grabbing set of trial results:
- All 3 pemvidutide dosing groups (1.2 mg, 1.8 mg, 2.4 mg) achieved the primary endpoint of relative and absolute reductions in liver fat, with a 68.5% relative reduction in liver fat content in subjects receiving 1.8 mg dose at 12 weeks of treatment
- Mean weight loss of 4.9% (placebo-adjusted 4.7%) in subjects without diabetes receiving 1.8 mg dose at 12 weeks of treatment
These results are accompanied by a relatively strong safety and tolerability profile.
When Stephen finishes, Jörn Schattenberg observes that unlike single GLP-1 agonists, this drug has a direct liver effect through its glucagon mechanism. Mazen Noureddin points out that liver fat reduction with pemvidutide is greater than what is typically seen in a drug with 4.3% weight loss. He suggests that the drug's positive impact on other metabolic parameters reflects a "whole body approach" more consistent with the multi-metabolic disease vision we often discuss on this podcast.
A recent string of press releases has presaged some of the most exciting, promising data of the last decade in NASH drug development. In this episode, Stephen Harrison reviews recent press releases from Altimmune, Akero, Poxel, Axcella and Intercept, while Jörn Schattenberg, Louise Campbell, special guest Mazen Noureddin and Roger Green share questions and impressions.
Last month, Altimmune presented its top-line results of a 12 week Phase 1B study of pemvidutide, a GLP-1/glucagon dual receptor agonist. After outlining the study design, Stephen summarizes the positive results of liver fat content reduction. Jörn takes interest in extending the spectrum of GLP-1s by targeting the liver directly with a glucagon agonist. Mazen notes liver fat reduction as disproportionately higher than what is typically seen in a 4.3% weight loss scenario. He expresses optimism that drug's positive impact on other metabolic parameters suggests a "whole body approach." The three then contextualize overall weight loss and liver fat content reductions.
The conversation shifts to Phase 2b results from Akero’s HARMONY Trial. HARMONY met its primary endpoint for both the 50mg and 28mg EFX dose groups, with 41% and 39% of EFX-treated patients experiencing at least a one-stage improvement in liver fibrosis with no worsening of NASH at week 24, (vs. 20% for the placebo arm). This leads Mazen to ask whether the future must rely on combination therapies. This leads Roger to recall a similar suggestion from Akero Chief Development Officer on a January 2021 episode. Stephen points out that future therapy might look not only at point-in-time combinations but also sequences of induction and maintenance therapies, as with many cancers.
The next set of data comes from DESTINY-1, a paired liver biopsy Phase 2B trial from Poxel. This study reports positive histology results for PXL065, a novel, proprietary deuterium-stabilized R-stereoisomer of pioglitazone. Stephen elucidates on the science of this drug and the mechanics of deuterium as a stabilizer. The study design consists of 117 subjects across four cohorts: three different doses versus placebo. The trial met its primary efficacy endpoint for liver fat content reduction at 36 weeks for all doses. Louise emphasizes the positives associated with delivering an oral mechanism. Roger expresses enthusiasm that introducing multiple modes of action to the market will create the energy and investment to drive a dynamic explosion of education and exploration in Fatty Liver diseases.
The panel continues exploring oral drugs by reviewing positive interim data from the Phase 2b EMMPACT Study by Axcella. They discuss the broad activity of this drug in addition to its well-tolerated profile and safety.
On a less optimistic note, Stephen outlines the Phase 3 results of the REVERSE trial by Intercept. This study focuses on evaluating the safety and efficacy of OCA in patients with compensated cirrhosis and, ultimately, did not meet its primary endpoint.
Dubbed a Wow! episode by the panelists, there are plenty more observations and supporting data points to be explored in this discussion. Surf on for the full report.
In this episode From the Vault, Surfers Roger Green and Louise Campbell are joined by Professor Ian Rowe to discuss the implications of the FDA approval of the ELF test.
For Ian, the ELF approval was the most important story of summer 2021. The test promises a brighter future for non-invasive tests and, eventually, decreased reliance on biopsy. Ian points out that transitioning from the ordinal results that biopsy generates (fibrosis score level) provide limited, unrealistic guidance in determining the probability of a downstream negative event (transplant, cancer, death). He contrasts this to continuous test results, including blood-based and device-driven tests, which provide clearer guidance about downstream risks. Louise Campbell adds her own reflections about the importance of inexpensive, blood-based tests to address the emerging NASH pandemic in poorer Third World Countries.
This conversation comes from Season 2, Episode 47. The discussion serves as an example of how people can view the value of a technological or analytical advance from vastly different perspectives. It also illustrates how the robust range of issues provides energy and new inquiries as fields progress. All of which contribute to the exciting prospect of heading into another year characterized by increasing innovation. Stay tuned and surf on.
After a month of major Fatty Liver medical meetings, Jörn Schattenberg, Louise Campbell and Roger Green explore emerging stories that will shape the next 6-12 months in Fatty Liver disease. In this final conversation, the group discusses the importance of combination NIT biomarkers in developing a viable system for treating patients. The key is that NITs provide a viable strategy for widespread patient screening and staging, whereas biopsy does not.
Roger also asks about several other issues that will come to the fore in the next year. The first item is the Nomenclature conference. Jörn describes it as a moving target with a clear split between the hemispheres. Asia is moving toward a concept more like metabolic-associated disease, however, Europe and North America are not. He notes that an ongoing process of consensus leaves him hopeful. Roger suggests that redefining the disease itself might lead regulators to disregard the vast amounts of research accomplished. Unfortunately, this has the potential to set the field back several years. Jörn agrees that it is imperative that any solutions do not push back drug or diagnostic approvals. The existing data and procedures around patient enrolment in trials remain clear.
The final question returns to the issue of what changes might take place over the next year. Each answer differs and continues themes found in the earlier conversations. Surf on for the group’s predictions.
After a month of major Fatty Liver medical meetings, Jörn Schattenberg, Louise Campbell and Roger Green explore emerging stories that will shape the next 6-12 months in Fatty Liver disease. This conversation speculates where potential bottlenecks in getting drugs to patients might emerge.
Louise points to payers as a significant barrier en route to product adoption. Roger suggests it depends on the healthcare system, but generally agrees with Louise. He references the past development of a Hep C treatment for a comparable example. Payers slowed adoption of drugs with clear long-term benefits due to the short-term cash outlays. Jörn also shares his belief that payers will be the source of bottleneck. He suggests that appropriate patient pathways and stratification provide the best counter-strategy. In response, Louise returns to her point that our health systems are not ready to implement Fatty Liver drug therapy yet, much less over the next 6-12 months.
The conversation then shifts to the more recent theme of a “combo-combo world,” coined by Mazen Noureddin in Season 3, Episode 43. Mazen had introduced the idea that combinations of biomarkers are necessary to diagnose and stage, while combinations of drugs provide optimal therapy. To finish, Jörn discusses the value of the consortia – LITMUS, NIMBLE, NAIL-NIT and Rohit Loomba’s Goldmine – in moving this issue forward.
After a month of major Fatty Liver medical meetings, Jörn Schattenberg, Louise Campbell and Roger Green explore emerging stories that will shape the next 6-12 months in Fatty Liver disease. This conversation focuses on exciting data they anticipate for multiple different drugs. They also discuss the implications positive drug trials and anticipated approvals will have for NAFLD treatment.
Roger begins by discussing the educational work Intercept was beginning before obeticholic acid received its complete response letter in 2020. He underlines the logic that doctors will be more eager to learn how to treat when given a reliable way to achieve results.
Jörn expresses specific enthusiasm about the future of FGF-21s as implicated by the recent Akero Phase 2b results. Roger then notes the promising data and/or approvals on the horizon for four different modes of action. He suggests that with these, the ideas of combination therapy and disease regression or resolution may become real for the first time. Louise agrees about the promise of the medications. However, she expresses strong concern that the diagnostic and patient management structures will not be in place before the drugs arrive. This shortcoming will slow the ability to bring these benefits to patients. Jörn returns to the excitement about the drugs and the idea that significant amounts of data may come as soon as November’s AASLD meeting. As the conversation ends, the group begins to explore where bottlenecks in getting drugs to patients might exist.
After a month of major Fatty Liver medical meetings, Jörn Schattenberg, Louise Campbell and Roger Green explore emerging stories that will shape the next 6-12 months in Fatty Liver disease. This conversation explores the role of multiple biomarker tests in the diagnostic process and how these might vary in the panelists’ home countries.
To begin, Louise notes that in the UK, many primary care physicians do not perform even basic liver tests, making it impossible to compute FIB-4. Roger questions whether publicizing of guidelines like the AACE or EASL guidelines will speed uptake of FIB-4. The guidelines recommend that front-line physicians not screen their T2DM patients for NAFLD, since 80+% will test positive. Instead, they recommend using a FIB-4 test to identify patients at risk due to current fibrosis. Roger then asks whether these guidelines will move into actual practice. Louise and Jörn each note that in their countries, front-line professionals are not required to perform liver enzyme blood work. Yet, these tests are pivotal for early liver screening. Louise doubts that change will come until after an expensive drug is approved, at which point there will be economic motivation to test. Jörn is more hopeful that with simple tests, he and other hepatologists can educate endocrinologist colleagues on the reasons to adopt this testing strategy over time.
As the conversation wraps up, Jörn begins to segue from the future of care pathways to the exciting future of drug development.
After a month of major Fatty Liver medical meetings, Jörn Schattenberg, Louise Campbell and Roger Green explore emerging stories that will shape the next 6-12 months in Fatty Liver disease. This conversation focuses on the need for different specialties to align in treating the complete range of non-communicable metabolic diseases.
Jörn starts the conversation with a personal highlight: he attended last month’s EASD meeting for the first time. Historically, few hepatologists attend this meeting. He views his attendance as indicative of a trend: hepatologists and endocrinologists working together on diabetes and NAFLD. Louise echoes the sentiment that liver health is gaining traction as a critical function of holistic patient management. However, she notes cardiology appears to be slow on the uptake. She also asserts that nurses should have a clear role in this discussion around holistic patient management.
Roger links collaborative energy to a completely different kind of energy formation: capital investment. He notes Akero’s recent filing for $230 million in equity to help bring efruifermin to market based on Phase 2b results. If this effort succeeds, it may signify that the financial markets are becoming more optimistic about NASH drugs after several years of extreme skepticism.
As the conversation winds down, Jörn returns to his original theme to discuss how endocrinologists have received the concept of liver disease as part of multimorbidity management in patients living with T2DM. He reports that the endocrinologists have been eager to learn the liver testing tools and metrics they should use. They require simple tests with high negative predictive values. That way, they know when it is time to send a patient to the hepatologist. This reminds Roger of Quentin Anstee’s talk in Dublin about the different roles that first and second biomarker tests play in the diagnostic process. The conversation finishes with Roger making a correlation between Quentin’s talk and Jörn’s recent experiences engaging with the endocrinology community.
The last month has witnessed several major Fatty Liver conferences and others that touch on NAFLD in the context of metabolic disease. One common theme has been the need for different specialties to align in treating the complete range of non-communicable metabolic diseases. In this episode, Roger Green, Jörn Schattenberg and Louise Campbell propose factors that have the potential to dramatically shift the force around fatty liver disease over the next six months.
Jörn starts the conversation with a personal example of a larger trend: he attended last month’s EASD meeting for the first time. Historically, few hepatologists attend this meeting, but Jörn believes his attendance is indicative of a trend: hepatologists and endocrinologists working together on diabetes and NAFLD. Louise echoes the sentiment that liver health is gaining traction as a critical function of holistic patient management, although cardiology appears to be slow on the uptake.
Roger links this collaborative energy to a completely different kind of energy formation: capital investment. He notes Akero’s recent filing for $230 million in equity to help bring efruifermin to market based on Phase 2b results. If this effort succeeds, Roger suggests that it may signify that the financial markets are becoming more optimistic about NASH drugs after several years of extreme skepticism.
Next, Jörn returns to his original theme to discuss how endocrinologists have received the concept of liver disease as part of multimorbidity management in patients living with T2DM. He reports that endocrinologists have been enthusiastic about the idea and eager to learn the liver testing tools and metrics they should use.
The group then responds to the AACE guidelines promoted last May. The guidelines recommend that front-line physicians not screen their T2DM patients for NAFLD, since 80+% will test positive. Instead, guidelines recommend using a FIB-4 test to identify patients at risk due to current fibrosis. Roger asks whether these will move into actual practice. Louise and Jörn each state that in their countries, front-line treaters are not required to perform liver enzyme blood work. These tests are pivotal for early liver screening. Louise doubts that change will come until after an expensive drug is approved, at which point there will be economic motivation to test. Jörn is more hopeful that with simple tests, he and other hepatologists can educate endocrinologist colleagues on the reasons to adopt this testing strategy over time.
The conversation shifts to speculation as to whether prescribers or payers will be the source of bottleneck in patient care pathways at the outset of a drug approval. The group generally agrees that pushback will come from the payers and that healthcare systems are not yet ready. They then look towards the social and political will to take action on the crisis. In response to Roger’s question, the group acknowledges the immense hurdles present in changing provider behavior over the next 6-12 months while stressing the importance of provider education and patient empowerment.
Finally, the group discusses the future of the recently coined “combo-combo world,” where correct diagnosis will require a combination of biomarker tests and treatment may require a combination of therapies. At the end, Roger asks what changes each member envisions. Surf on to find out.
The 2022 NAFLD Summit presented a range of perspectives and insights on fatty liver and metabolic diseases. In Season 3, Episode 46, program speakers Mazen Noureddin, Sven Francque and Hannes Hagström join Roger Green on-site from Dublin to review their reactions immediately after the conference ended. The panelists note the impact of weight change and lifestyle modification in clinical trials while utilizing insights from the bariatric and diabetes fields.
In this episode From the Vault, Roger Green, Stephen Harrison, Ali Aminian and Wayne Eskridge discuss how weight loss and GLP-1s or Double/Triple Agonists in relation to SPLENDOR. This conversation comes from Season 2, Episode 61.3.
Season 3, Episode 46 is sponsored by Resoundant, a Mayo Clinic company and the developers of Magnetic Resonance Elastography. MRE is widely available with over 2000 locations worldwide, and can be done as a low-cost, rapid exam in just 5 minutes. Together with PDFF, this quantitative exam is called an Hepatogram – a powerful non-invasive alternative to liver biopsy in many cases. For more information, visit www.resoundant.com on the web.
The 2022 NAFLD Summit presented a range of perspectives and insights on fatty liver and metabolic diseases. Program speakers Mazen Noureddin, Sven Francque and Hannes Hagström join Surfer, Roger Green, on site from Dublin to review their reactions immediately after the conference ended. This final conversation begins with Roger calling attention to a debate around NITs that took place on the opening day of the meeting. Mazen revisits what he has described on this podcast as the coming “combo-combo” world. The group generally agrees that biomarkers in primary care ought to be simple, cost effective and accessible. However, Sven utters a word of caution: while acknowledging the positive potential of NITs, it is still important to evaluate its limitations.
The episode concludes with a round of final reflections. Roger asks for panelists to forecast the most important thing that will have changed between now and when we return for the NAFLD Summit 2023. Surf on to find out what the panel predicts.
This episode is sponsored by Resoundant, a Mayo Clinic company and the developers of Magnetic Resonance Elastography. MRE is widely available with over 2000 locations worldwide, and can be done as a low-cost, rapid exam in just 5 minutes. Together with PDFF, this quantitative exam is called an Hepatogram – a powerful non-invasive alternative to liver biopsy in many cases. For more information, visit www.resoundant.com on the web.
The 2022 NAFLD Summit presented a range of perspectives and insights on fatty liver and metabolic diseases. Program speakers Mazen Noureddin, Sven Francque and Hannes Hagström join Roger Green on-site from Dublin to review their reactions immediately after the conference ended. In this conversation, the panelists examine the impact of weight change and lifestyle modification in clinical trials while utilizing insights from the bariatric and diabetes fields.
This conversation continues the issue of Hawthorne effects in trial design. Hannes starts by noting we can learn from obesity trials – and also from TV shows like “Biggest Loser” – that people regain weight without continued support. Roger shares a thought he believes might have come from absent co-host Louise Campbell, recalling the immediate impact FibroScan has on illustrating results and influencing patient motivation. Sven notes that the issue of lifestyle management in a NASH trial has been a significant issue for the Liver Forum and other supportive groups in terms of trial design and also the power calculations that shape trial size. Mazen closes the discussion by stating that recent meta-analyses show that placebo rates tend to run around 20% and that this might be the right placebo result for power calculations. As the conversation winds down, he shares his guiding principle for these issues: “Prepare for the worst and hope for the best.”
This episode is sponsored by Resoundant, a Mayo Clinic company and the developers of Magnetic Resonance Elastography. MRE is widely available with over 2000 locations worldwide, and can be done as a low-cost, rapid exam in just 5 minutes. Together with PDFF, this quantitative exam is called an Hepatogram – a powerful non-invasive alternative to liver biopsy in many cases. For more information, visit www.resoundant.com on the web.
The 2022 NAFLD Summit presented a range of perspectives and insights on fatty liver and metabolic diseases. In this conversation, the panelists explore issues around clinical trial design, focusing specifically on the value of Phases 2a and 2b and whether improvement in patient self-management during trials is a research artifact or a replication of reality.
This conversation addresses two issues in clinical trial design. First, Roger Green draws on the Session 9 discussion of failed trials to ask which is the right way to proceed when a drug in a Phase 2b trial fails to reach its primary endpoint but a subanalysis reveals a second possible path to Phase 3. He notes that this was the case with elafibranor, one of the Session 9 case studies, as well as obeticholic acid, a drug whose Phase 3 trials met its efficacy endpoints but is not yet approved due to regulators’ seeming perception that it lacks an acceptable cost:benefit ratio. The group points to reasons these may have been solid decisions before noting that the market and scientific community both expect higher performance from drugs today than they did several years ago. Mazen Noureddin asks whether exceptionally promising drugs might consider moving directly from Phase 1b to Phase 3; the group agrees that Phases 2a and 2b will have value for virtually every drug at this time.
The final question comes from Roger, who asks whether improvements in patients’ diet and lifestyle during the clinical trial constitute a “Hawthorne effect,” as some stated on Saturday morning. He notes that in the literature, a Hawthorne effect is a change that might affect clinical trial results but will have no meaning in day-to-day practice. By that standard, improvements in patients’ diets and lifestyles do not constitute a Hawthorne effect since we want to effect these behaviors in all patients. Mazen Nouredin disagrees, noting that after trials, patients’ behaviors tend to revert to pre-trial levels, thus making improved behavior a confounding factor in analyzing trial results. The group comes to no clear consensus on this issue.
This episode is sponsored by Resoundant, a Mayo Clinic company and the developers of Magnetic Resonance Elastography. MRE is widely available with over 2000 locations worldwide, and can be done as a low-cost, rapid exam in just 5 minutes. Together with PDFF, this quantitative exam is called an Hepatogram – a powerful non-invasive alternative to liver biopsy in many cases. For more information, visit www.resoundant.com on the web.
The 2022 NAFLD Summit uniquely presented a range of perspectives and insights on fatty liver and metabolic diseases. Program speakers Mazen Noureddin, Sven Francque and Hannes Hagström join Surfer, Roger Green, on-site from Dublin to review their reactions immediately after the conference ended.
At the outset of this episode, the group discusses the benefits of participating in a smaller conference more focused on the challenges presented by the field of NAFLD. Mazen likens the NAFLD Summit to NASH-TAG, asserting that these specific conferences advance the field and address deeper layers around the issues that matter most.
Mazen goes on to raise the issue of glycemic control and the impact of glycemic control on NASH drug performance. This bleeds into a brief point about the value of simply stopping fibrosis progression instead of the need to prove regression. He then identifies two sessions he considered particularly valuable: the Saturday morning autopsy of failed Phase 3 trials and therapeutic discussion about drugs at different stages in development. This segues into a discussion of optimism derived from the recent Akero and Altimmune results. In terms of Altimmune, Mazen asks whether the drug should go directly from Phase 1b to Phase 3. The panel generally believes that Phases 2a and 2b have value for virtually all development drugs. Further, the panel agrees that the presentations on three failed Phase 3 trials were richly valuable and that each offered its own clear lessons for researchers.
This episode is sponsored by Resoundant, a Mayo Clinic company and the developers of Magnetic Resonance Elastography. MRE is widely available with over 2000 locations worldwide, and can be done as a low-cost, rapid exam in just 5 minutes. Together with PDFF, this quantitative exam is called an Hepatogram – a powerful non-invasive alternative to liver biopsy in many cases. For more information, visit www.resoundant.com on the web.
The 2022 NAFLD Summit presented a range of perspectives and insights on fatty liver and metabolic diseases. Program speakers Mazen Noureddin, Sven Francque and Hannes Hagström join Surfer Roger Green, on-site from Dublin to review their reactions immediately after the conference ended.
In this episode, the panelists discuss presentations and sessions they found particularly compelling. The group notes Session 7 from Day 2 as an attractive line of topics covering overlooked issues in clinical trials. While difficult to quantify the impact on clinical trials, the data supports approximately 10% of patients with NAFLD underreport alcohol consumption. Hannes’ own presentation at the NAFLD Summit covered this subject. However, his concern lies in possible patient reluctance to enter a clinical trial in response to ‘the elephant in the room.’ Roger and Mazen are optimistic that simpler, faster biomarkers will help overcome this challenge. Mazen also shares his interest in Sven’s presentation which provided an introduction to cardiovascular comorbidities within the same theme of Session 7.
Next, Sven focuses on the strengths of consulting with non-hepatologists on how the treatment of comorbidities affects NAFLD. They provide different, more holistic perspectives than one typically hears in a hepatology-centric event. Recently, this podcast has begun to focus on multi-organ metabolic effects more frequently. Patients rarely face NAFLD or NASH as an isolated liver problem. More often, other metabolic diseases ride along with it. Sven emphasizes that the researcher must keep the entire scope in focus when designing and executing NASH trials.
The 2022 NAFLD Summit presented a range of perspectives and insights on fatty liver and metabolic diseases. In this episode, program speakers Mazen Noureddin, Sven Francque and Hannes Hagström join Surfer, Roger Green, on site from Dublin to review their thoughts and key takeaways immediately after the conference ended. Roger starts by asking each to choose and elaborate on one presentation or session of particular interest. Hannes is the first responder, establishing Session 7 from Day 2 as an attractive line of topic covering overlooked issues in clinical trials. While difficult to quantify the impact on clinical trials, the data supports approximately 10% of patients with NAFLD underreport alcohol consumption. Hannes’ own presentation was tied to this subject. However, his concern lies in possible patient reluctance to enter a clinical trial in response to ‘the elephant in the room.’ Roger and Mazen join to commend Hannes on the presentation, noting the optimism that simpler, faster biomarkers lend to the matter. Mazen extends commendations to Sven also, for his introduction and exploration of cardiovascular comorbidities within the same theme of Session 7.
Next, Sven introduces his interest in the subsequent and closing session on Friday afternoon. Specifically, he contemplates the strengths of consulting with non-hepatologists on how the treatment of comorbidities affects NAFLD. Moreover, some of those participating endocrinologists, obesity physicians and other interdisciplinary professionals possess long-standing expertise in metabolic diseases, but not necessarily NASH. They provide different, more holistic perspectives than one typically hears in a hepatology-centric event. Roger notes that recently, this podcast has begun to focus on multi-organ metabolic effects more frequently. As the group notes, patients rarely face NAFLD or NASH as an isolated liver problem. More often, other metabolic diseases ride along with it.
The conversation continues to highlight what differentiates NAFLD Summit from other major liver meetings. Mazen states that both the NAFLD Summit and NASH-TAG allow for a deeper dive into more provocative discussions around how to advance the field. Then, Hannes proposes the group consider stability of fibrosis worthy of investigation as an outcome. Mazen replies that preventing decompensation and associated outcomes can serve as a goal that makes fast Phase 3 cirrhosis trials possible.
Next, the group assesses Session 9 from Friday, a series of case studies on why trials fail. The panel agrees that the presentations on three failed Phase 3 trials were richly valuable and that each offered its own clear lessons for researchers.
Following, the group examines weight change and lifestyle modification, referencing insights from the obesity and diabetes fields. Roger plays the role of Louise, elucidating the immediate impact FibroScan has on illustrating results and influencing patient motivation. Improvements in patient management do have a role in contributing to better outcomes. On the other hand, there is also the pressure of minimizing placebo rates in trials. Mazen is confident in the existing data and analyses that set precedent for placebo response rates.
Finally, Roger calls attention to a debate around NITs that took place on the opening day. Mazen Noureddin revisits what he has described on this podcast as the coming “combo-combo” world. However, Sven utters a word of caution: it is still important to evaluate the limitations of NITs. The episode concludes with a round of final reflections. Tune in and surf on for the full review.
In Season 3, Episode 19, the content focus looks at what the retrospective analysis from the NAIL-NIT consortium can achieve in terms of moving the shift beyond the biopsy in NASH diagnostics forward.
This conversation starts with Stephen discussing how challenging it was to develop initial FDA test criteria for evaluating NASH drugs. Many years later, he notes, we have learned how flawed these criteria were, several in ways we cannot fix, but we need to do better. He relates this to what the British author Rupert Sheldrake describes as “morphic resonance” or mysterious telepathy type interconnections between organisms and collective memories within species. One thing leading hepatologists have learned is that you can look at a liver or liver data and get a clear since you are looking at NASH, but it is harder to generate and vet consistently clear data on this point. He points to the REGENERATE trial as a place where specific data analysis did not reflect the gestalt impression and says, “that is what we need to get beyond.”
Louise Campbell interjects a very different kind of question, asking whether the NAL-NIT analyses can include questions that patients answer on initial screening in pursuit of AI-driven analyses of these questions to screen patients into or out of further tests..an idea that draws an immediate, enthusiastic response from Naim Alkhouri. In the end, the discussion turns light-hearted and focuses on how many papers the panelists will have to produce in the first year of the program.
In this episode, the group covers the Day Two program and offers final thoughts on the Paris NASH 2022 review.
The conversation starts with Louise introducing the discussion around estrogen replacement therapy and fatty liver in post-menopausal women. She notes this an area of opportunity for improving women’s health.
Next, Arun Sanyal’s science lecture on NITs is discussed. The lecture is noted to be less about groundbreaking science and more so a clear description of the thinking behind developing an NIT diagnostic pathway. This pathway starts with FIB-4 and goes into more accurate (and expensive) tests for patients that FIB-4 does not rule out.
From there, the conversation shifts to one last discussion about the ways that liver disease is central in the cluster of chronic non-communicable metabolic diseases. Finally, Roger offers the closing question. Each responds with their feelings toward the future of NASH, NAFLD, metabolic disease, and interdisciplinary collaboration.
Listen on for the Surfer’s, and Jeff McIntyre’s, final thoughts on Paris NASH 2022.
This episode addresses the other talks in Session 5 focusing on clinical trial innovation, after Frank Anania’s opener.
Roy Sabo presented a cogent, comprehensible discussion of the value of adaptive trial strategies. Roger relates the presentation to a conversation on the NASH Tsunami last month with Stephen Harrison. Stephen introduced an example of adjusting FibroScan thresholds to boost the number of patients who could enter clinical trials. Roger commends Sabo on the “wizardry Bayesian statistics.”
The following two talks discussed organizing patient databases in ways that simplified trial recruitment and had the potential to reduce screen fail rates. Lastly, the group explores the pros and cons of educating patients on improving self-care. The benefit is that it creates a larger, ready-made patient pool and improves overall health. The drawback is that it increases placebo rates in clinical trials, thereby requiring drugs to perform better to demonstrate statistical difference. However, in a world of well-informed patients practicing aggressive health self-management, there should be the expectation that drugs offer better performance.
The conversation finishes with covering the rest of the day one program.
The episode starts with Louise sounding an alarm about the rate of growth for cirrhosis and bridging or advanced cirrhosis. She is concerned that as more data is collected, an increasing number of lives fail to be served with the passage of time. She then mentions a talk by Oxana Drapkina from Session 1 about how the Russian system operates. On the surface, this sounds to be more efficient than Western approaches.
Next, Jeff and Jörn share their thoughts and satisfaction on the closing session, in which both participated. The diversity of regional challenges and the varied positions of the panelists led to a lively and far-reaching discussion. In response to a question from Jörn, Jeff expands on what he learned while working on food policy in the Obama White House.
In the final part of this episode, Roger raises a few issues of interest. He discusses the ability to educate and work more quietly in Congress than in public venues. He also mentions the value of educating physicians to think of Fatty Liver issues when treating other metabolic patients. Louise joins to consider the idea that while different specialties look down organ silos, reality often presents an integrated metabolic challenge.
The episode begins with the panelists - Jörn, Louise, Jeff McIntyre of GLI and Roger - discussing one thing each found particularly striking at the recent Paris NASH meeting.
Most comments centered around three themes:
- A general appreciation of the quality and diversity of talks at Paris NASH.
- Disappointment with the regulatory response from Frank Anania of FDA on the question of moving beyond biopsy and changing the shape of conditional drug approvals.
- The “dynamic tension” between forces pushing for rapid progress vs. forces slowing pace of development.
The group further considers the influence of providers, manufacturers and patients versus that of regulators and payers. Jeff and Roger agree that payers are likely to present the last- and likely highest- barrier to rapid progress on prescription medicines and testing.
The importance of integrating the NAFLD and NASH field within a wider scope of metabolic health was emphasized at the 8th Paris NASH Meeting. Last week, Surfers Roger Green, Louise Campbell and Jörn Schattenberg were in attendance alongside patient advocate and episode guest, Jeff McIntyre.
The conversation starts with Roger asking the group about one thing each found particularly striking from the meeting. Jörn responds first, noting his many appearances across the history of the event. He thinks this year’s dominating theme to be the engagement of regulatory questions that address moving beyond biopsies and conditional drug approval. Jeff joins to echo this takeaway, adding that he is intrigued by the multinational dynamics of the meeting. Next, Louise recalls a more specific crux. In response to an industry roundtable, she suggests that with the wealth of data provided from clinical trials it is now time to consider changing endpoints. Lastly, Roger offers his general thoughts on witnessing the shifting tensions between the scientific and patient advocate positions and the regulatory and payer responses. The group then compares the American and European positions on moving the field toward a more metabolic perspective. They consider where this pressure comes from in terms of regulators, patients, payers, politicians and employers.
Moving on, Roger asks the group for an example of one particular talk or panel that grabbed their imagination and why. Louise returns to the statistics surrounding NASH. She reminds that while the field searches for more data, an expected rise of 110-125% in advanced liver disease and mortality by 2040 is underway. Given the influence of obesity on this rise, Louise highlights the role of allied health professionals in providing lifestyle guidance to mitigate disease progression from an earlier stage.
In the closing session, both Jörn and Jeff reflect on participating in discussions surrounding the role of the patient voice and developing a global strategy for NASH. This leads the group to explore the potential for public advocacy in the field of NAFLD and NASH. Afterwards, Roger brings focus to educating physicians and other healthcare professionals on the nature of metabolic disease. By developing an understanding of the multifaceted application of many drugs in a metabolic context, the wait for an F1 or NAFLD drug approval can be possibly eliminated altogether. Louise adds that a pivot is required to move away from organ-centric thinking.
Next, the group provides their thoughts on Session 5, starting with response adaptive trial design to pick the best dose. Roger and Jörn share ideas on clinical trial criteria and the use of Bayesian priors in enrichment strategies. Jeff also revisits the role of patient involvement in this topic.
Roger then suggests the four go through and connect missing dots between sessions covered in the conversation thus far. After that, the final response:
Louise looks toward a bright future with metabolic coordination. She believes patients are key in developing person-centric approaches.
Jörn believes that addressing multiple organ systems is the way forward and that it is necessary to partner with other disciplines.
Jeff feels grateful for his participation as a patient advocate. He says he is looking for the experience of the science, which in the end feels positive to him.
Roger reiterates the importance of investigating these discussions as Paris NASH does. “One thing that became clearer to me in this meeting than it's ever been before, is that this is all about metabolic disease.” He is hopeful.
Surf on for the full review.
This week, Surfing the NASH Tsunami discusses a preview of the 8th Paris NASH Meeting taking place on September 8th & 9th, 2022. Paris NASH is a meeting for basic science and interdisciplinary thinking. Key opinion leaders from both sides of the Atlantic come together to present pivotal learnings and host exciting discussions on fatty liver diseases.
In this conversation from September, 2021, Jörn Schattenberg, Stephen Harrison and Roger Green review some highlights from last year’s Paris NASH conference. This conversation is the summary of conference high points and lessons. From the second day, Jörn chose to mention several talks he felt made particularly important points. This includes a session, “NASH Around the World,” that demonstrates the scale of the global challenge by looking at major countries around the world. Finally, Stephen and Roger join Jörn in selecting one key takeaway from the meeting and their conversation together.
Roger starts by asking Jeff to describe his role in the NAFLD Summit and to discuss any other presentations of interest outside of his own. Jeff shares that he will be talking about evolving models of care and future implications. His interest in the session stems not just from his presenting, but from the session title, "Epidemiology, Disease Modifiers and Models of Care," and the opportunity it presents to, as Jeff puts it, "hammer home" the importance of integrated care and pathways. He also mentions the importance of the sessions covering NITs, which are pivotal to the way forward, new approaches to lifestyle modification and drug clinical trials and development.
The conversation shifts Jeff's other activity in Dublin: meeting with industry and other colleagues to build momentum for an upcoming meeting at Wilton Park to build on the momentum of the 2021 global consensus statement on NAFLD. (This was the topic of Season 2, Episode 59.)
The conversation veers into two other topics of relevance. First, Jeff draws a link between the importance of viewing liver disease in a truly multi-disciplinary context with the broadening of presentation topics at major meetings. He points out that if we want colleagues from other medical specialties to join in efforts to contain the coming NAFLD pandemic, medical meeting agendas must include enough topics of interest to them to broaden the prospective set of attendees. The second issue involves engaging the WHO to incorporate liver disease into its global health priorities.
Roger Green starts this interview with Jeff Lazarus by asking what Jeff has been focusing on since the Barcelona conference in May.
Jeff describes his extensive daily efforts to develop and garner support for a global consensus strategy on COVID-19, similar to his work on a global consensus statement on Fatty Liver disease. (This was the topic of Season 2, Episode 59.) Like the Fatty Liver work, his COVID-19 consensus work included representatives from over 200 countries with an array of public, academic and not-for-profit portfolios. However, he suggests that the high levels of agreement and, sometimes, virtually unanimity evident in the Fatty Liver work was impossible to match on an issue as immediate and terrifying as COVID-19.
Roger then asks about the NAFLD Nomenclature Conference. Jeff describes the conference as a midway point for a Delphi process to explore the prospect of assigning a new name(s) in the description of fatty liver diseases. Jeff describes the six principles any name change must achieve:
- Affirmative
- Accurate
- Adaptable
- Adoptable
- Applicable
- Able.
The rest of this conversation covers prospects for success of the Nomenclature effort and the nature of the challenges ahead.
The group concludes the preview of the upcoming Paris NASH conference after taking a thorough look at the diversity of topics in Session 5. Roger Green poses the closing question: What insights or energy would you like to see come out of this event? What is the immediate response, and what’s going to stick after 3 to 5 years?
Jörn Schattenberg indicates his interest in the future of drug development and what implications this meeting will have on it. In a more immediate sense, he notes an interest in the more recent learnings of disease biology covered in Scott Friedman’s basic science sessions.
Louise Campbell anticipates an immediate integrated response as a result from this meeting. She suggests a joint meeting between specialists to tease out the implications of liver health in a holistic outcome. “We don't try and repair a car without opening the bonnet to look at the engine - but we're trying to solve diabetes, cardiovascular disease and all of the other linked metabolic diseases without taking the lid off the liver.”
Rachel Zayas looks for a joint response across specialities to activate steps to break down thinking in terms of “organ silos.”
Roger provides his final thoughts by way of a double entendre on the word “global.”. Global refers to how widely NAFLD-associated challenges vary in different parts of the world, but it also refers to the liver as part of a holistic web of non-communicable metabolic diseases. He concludes, “We need to understand how we're going to address this in different parts of the world, but as the challenges vary, we also need to understand how we're going to address the whole body in the context of the liver.”
This conversation picks up focusing on the program’s opening session: Epidemiology and Public Health. Roger, Louise and Jörn begin to unpack the field of NASH in terms of adopting a holistic, metabolic approach. Roger asks, “How much of NASH are we thinking about in a holistic metabolic sense versus how much do we pay lip service to that, but really focus on the liver?”
In response, Rachel poses a strong question for the surfers. “What do you hope to get out of this session with an integrated approach between specialties? And how is that going to move the field forward?” Jörn takes the first shot. He suggests that data and insights might point the field toward pathway refinement and help identify where patients are lost on this journey. Louise agrees, noting one specific point of challenge: liver patients frequently present too late in the journey.
Next, Roger offers his take. “One of the problems the liver has always had is that nobody knows how to measure fatty liver disease.” How will the field move forward? He suggests the way to appreciate the importance of fatty liver disease is to demonstrate how many metabolic diseases and deaths it contributes to, using direct links. “If anybody can provide data that says, if you see this in the heart, the kidney, wherever, that's likely to be a liver issue or more likely to be a liver issue.” From here, the field can start to broaden the context of liver health in a more holistic sense.
Rachel then provides her answer. She is looking for strategies to link fatty liver with cardiovascular disease. Suggesting the establishment of if, then statements, Rachel looks to elucidate what actionable results can be taken with those links.
In this conversation, Roger Green, Louise Campbell, Jörn Schattenberg and Rachel Zayas share their particular interests in what’s to come from the 6 sessions hosted at this year’s Paris NASH Meeting.
Rachel identifies a presentation in Session 2: Clinical Aspects, titled Controversy: are HIV infected patients more at risk of NASH? She notes the specific challenges faced by HIV patients and shares her hope the prompt leads to speculation on how to improve patient stratification. Rachel also brings forth a concept of moving beyond ideas of personalized medicine to what she describes as a more “intentional approach.”
Staying in Session 2, Jörn draws anticipation toward a talk by Cyrielle Caussy titled, Type 2 diabetes sub-populations with varying outcome profiles. He is curious to learn something about which type two diabetes patients are more severely liver diseased. Jörn also mentions an interest in the last remaining presentation in Session 2, with Kris Kowdley discussing the natural history and clinical outcomes in adults with NAFLD - lessons from cohort studies and placebo arms of trials.
Next, Louise calls attention to the opening session and her interest in the integration of the liver under cardiometabolic health. This topic will be presented by Faiez Zannad. Additionally, Louise mentions NASH PASS. In Session 5, Marcus Hompesch discusses three years of data & experiences on a metabolic disease focused patient registry and biobank supporting biomarker and drug development research.
Also in Session 5, Frank Anania of the FDA presents on a subject recently explored in last week’s episode 43: How to approach combination therapies for NASH. Following, Roy Sabo discusses response adaptive trial design to pick the best dose. This piques Roger’s interest.
The tone of this conversation conveys a sense of excitement about what this meeting will bring.
The 8th Paris NASH Meeting takes place on September 8th & 9th, where key opinion leaders from both sides of the Atlantic come together to present pivotal learnings and host exciting discussions on fatty liver diseases. Surfers Roger Green, Louise Campbell, and Jörn Schattenberg are joined by Rachel Zayas to discuss this year’s program and provide preview commentary on talks and sessions of interest.
Roger opens the floor by asking everyone to highlight what specifically stands out to them on the program to look forward to. “Brave one go first.”
Rachel notes a presentation in Session 2: Clinical Aspects, titled Controversy: are HIV infected patients more at risk of NASH? Emerging data and insights will be discussed as to why the prevalence of NAFLD, NASH and subsequently fibrosis present higher in HIV-infected patients in comparison to the general population. Rachel hopes the prompt leads to speculation on how to improve patient stratification. She suggests the field is moving beyond ideas of personalized medicine to what is described as a more intentional approach. Jörn echoes Rachel’s interest in this topic. There is the need to address not only individuals, but also a group of overlooked patients that call for an intentional and stratified investigation into potentially shared biomarkers. Session 2 also features a discussion on type 2 diabetes sub-populations with varying outcome profiles, solidifying the Clinical Aspects leg as a ‘can’t miss’ for the whole group.
Next, Louise calls attention to the opening session and her interest in the integration of the liver under cardiometabolic health. “That's where we're going to find the breadth and depth of patients for future NASH studies.” She asserts that a larger recruitment to clinical trials will be required in the next 3 to 5 years to move the field forward.
Roger relates the relevance of last week’s episode on finding the right combinations for NASH therapy. Friday afternoon features a look into the current status and future directions in NIT-based drug development and clinical management of NASH.
The conversation shifts to comparative outcomes of the Barcelona meeting and its focus on pathways before transitioning into part 2 of this episode: a one on one interview with Prof. Jeff Lazarus. Much of Jeff’s summer was spent working in preparation for the impact COVID will have on the northern hemisphere this autumn. However, he also managed to attend the NAFLD Nomenclature Conference in Chicago. The conference is described as a midway point for a Delphi process that explores the prospect of assigning a new name(s) in the description of fatty liver diseases. What was determined is that should a name change occur, it needs to be organized through global consensus and consistent with the following 6 principles:
- Affirmative
- Accurate
- Adaptable
- Adoptable
- Applicable
- Able
Roger believes that the meeting was successful at strengthening consensus on this topic. He then asks Jeff to describe his role in the NAFLD Summit and to mention any other presentations of interest outside of his own. Jeff shares that he will be talking about evolving models of care and future implications. Specifically, he is also interested in attending discussions and panels around the impact of NITs in addition to the topic of personalized medicine. Likewise, Roger expresses an interest in emerging technologies before offering a final question - or, rather, a request for commitment. Will Jeff return to the podcast to disclose what occurred at the Wilton Park meeting this October? It seems he might, after a few weeks digestion. Stay tuned, stay safe and surf on.
This conversation from The Vault - Season 3, Episode 25.3 is part of a broader overview of NASH drug development in 2022, led by Stephen Harrison and Jörn Schattenberg. It starts with Louise Campbell asking whether design and management of the ongoing trials will provide sufficient granularity on matching patient types to medications or drug classes. Stephen Harrison notes that we have not paid sufficient attention to this issue historically. In fact, he notes a range of key variables we do not explore at baseline: genotype disease markers like PNPLA3, microbiome and non-Caucasian population segments, to name three. He also notes that some promising drugs have been killed because of trial design issues. In the end, he returns to core positive concepts: combination therapies, looking for agents with multiple positive metabolic effects and safety.
At this point in the conversation, Stephen’s transmission starts to fail. Eventually, he leaves the conversation and focus shifts to cirrhosis.
This episode from the Vault is sponsored by Madrigal Pharmaceuticals.
The group investigates potential for different combination packages, beginning with Roger’s suggestion for an oral semaglutide. Naim notes that there are other combination trials in the works that may provide more insight.
The episode then wraps up with Roger’s final question: in seven years, what percentage of patients being treated for NASH fibrosis, non-cirrhotic then cirrhotic, will be treated using combination therapies? Naim thinks the majority of patients with NASH cirrhosis will be on combination therapy, and the majority of patients with F2 or F1 fibrosis will be on monotherapy. He also thinks F3 will see a trend of adding more agents over time to prevent progression to cirrhosis. Mazen suggests in seven years we will not get to combo for NASH patients because of regulation, partnership, and logistics. Louise settles for a position between Naim and Mazen. Jörn highlights that many hurdles remain, especially in identifying these patients. Roger agrees that these diagnostics will be hard to scale over the next seven years. He also imagines there to be less combination packages and more step therapy.
This conversation begins with a broader look at the strategies behind developing combination agents and the role these combination therapies will play in what Mazen Noureddin describes as the coming “combo-combo” world.
The group agrees that 2 or 3 agents are the most they can see in a combination therapy at this time. They all agree that some patients will require combination therapies while others will succeed with monotherapies. This will be linked with disease severity. Naim also shares another long term study he is working on.
The discussion shifts to the challenges behind collaborating in a field that, as Naim puts it, “no one has figured out what to do with.” Mazen calls on the “larger companies” to work with the smaller ones to make these studies more common, noting that the economics and risk profiles of smaller companies require them to focus on getting a single drug to market as quickly as possible. Naim notes that precedent has taken form in Hepatitis C. It was very difficult to treat and different companies’ drugs were combined for a while until each company figured out their own combination and that collaboration stopped.
A debate next emerges when Naim describes LEGEND, a trial combining the promising PPAR agonist with the SGLT-2 agent, empagliflozin. Naim describes empa as an excellent agent to counteract potential weight gain with lani. Mazen shares his belief that the trial should have combined lani with a drug that provides greater weight loss, possibly a GLP-1 agonist or dual agonist. Roger suggests it depends on the target: liver and metabolic disease targeting might lead to a PPAR/GLP-1 combination, while a more holistic look at metabolic outcomes might prefer SGLT-2s for their proven beneficial effects on kidney and cardiovascular diseases.
Naim opens this conversation with his hope for finding eventual combination therapies that begin to realize a cure for NASH in some patients. In particular, he is encouraged to see so many patients achieve greater than 30% relative fat reduction in such a short study. Louise notes that the ability to show patients “real-world results” quickly will motivate them to maintain therapy and lifestyle modification.
The discussion shifts to the inclusion of NITs in these combination therapies, and the need for sound pricing strategies. Naim proposes a 6-month “futility” standard: if the drug does not provide results in 6 months, discontinue. Roger notes the importance of combination therapy in a disease that has so many theoretical target points and pathways within the liver.
This discussion begins with Naim offering an in-depth look into the mechanics of the recently published combination study. He explains that “semaglutide hits every point” in terms of effects on metabolic syndrome, cardiovascular outcomes, obesity and liver fat, but it has not yet been proven in monotherapy to regress fibrosis. Gilead Sciences had three agents whose potential anti-fibrotic effects the company wanted to explore fully, so Gilead and Novo Nordisk, which owns semaglutide, formed a partnership to develop these drugs.
One agent, selonsertib, turned out to be ineffective, but the other two, the FXR agonist cilofexor and the ACC agent firsocostat proved efficacious in combination with semaglutide. Naim goes on to describe the mechanics of the study and presents results demonstrating that even in a six-month trial, the triple therapy proved efficacious with a favorable side effect profile.
Jörn notes one very important aspect of combination agents: by requiring lower levels of each individual agent, they have the potential to exhibit superior safety and side effect profiles that a higher-dose monotherapy might.
The rest of this conversation features additional comments by Mazen, namely addressing the short duration of the study. He suggests that if extended, the study quite possibly had more positive results to be shown, namely, through further weight loss. Mazen also raises an intriguing prospect with an interesting acknowledgment: this is an open-label study with neither biopsies nor a placebo arm. However, he suggests, this kind of design will become far more prevalent in a future when one agent in the study has already been approved and is widely used with patients.
This episode explores the future of combination agents in NASH Therapy. First author Naim Alkhouri and last author Mazen Noureddin join the Surfers to discuss their recently published article, Safety and efficacy of combination therapy with semaglutide, cilofexor and firsocostat in patients with non-alcoholic steatohepatitis: A randomised, open-label phase II trial (JHEP, 2022). While the conversation starts by focusing on this article, the discussion itself takes a far broader look at the strategies behind developing combination agents, the likely role these combination therapies will play in treating patients, and, more generally, what Mazen Noureddin describes as the coming “combo-combo” world.
At the outset, Naim notes that while this study was published in 2020, it was first presented at AASLD in 2020. The rationale? As he explains, “semaglutide hits every point” in terms of effects on metabolic syndrome, cardiovascular outcomes, obesity and liver fat, but has not yet been proven in monotherapy to regress fibrosis. Novo Nordisk and Gilead Sciences had formed a partnership to develop NASH drugs, and Gilead had two agents with anti-fibrotic effects, the FXR-agonist cilafexor and the ACC agent firsocostat, that might regress fibrosis.
This conversation is dense with excellent questions and important observations. Here are some of them:
Jörn notes one very important aspect of combination agents: by requiring lower levels of each individual agent, they have the potential to exhibit superior safety and side effect profiles that a higher-dose monotherapy might. In agreeing, NAIM notes with particular enthusiasm how many patients achieved greater than 30% relative fat reduction in such a short study.
Mazen raises an intriguing prospect by starting with an interesting acknowledgment: this is an open-label study with neither biopsies nor a placebo arm. However, he suggests, this kind of design will become far more prevalent in a future when one agent in the study has already been approved and is widely used with patients.
Louise notes that the ability to show patients “real-world results” quickly will motivate them to maintain therapy and lifestyle modification.
Naim proposes a 6-month “futility” standard: if the drug does not provide results in 6 months, discontinue.
Roger notes the importance of combination therapy in a disease that has so many theoretical target points and pathways within the liver.
Mazen calls on the “larger companies” to work with the smaller ones to make these studies more common, noting that the economics and risk profiles of smaller companies require them to focus on getting a single drug to market as quickly as possible.
A debate emerges when Naim describes LEGEND, a trial combining the promising PPAR agonist with the SGLT-2 agent, empagliflozin. Naim describes empa as an excellent agent to counteract potential weight gain with lani. Mazen shares his believe that the trial should have combined lani with a drug that provides greater weight loss, possibly an GLP-1 agonist or dual agonist. Roger suggests it depends on the target: liver and metabolic disease targeting might lead to a PPAR/GLP-1 combination, while a more holistic look at metabolic outcomes might prefer SGLT-2s for their proven beneficial effects on kidney and cardiovascular diseases. The group agrees that 2 or 3 agents are the most they can see in a combination therapy at this time. They all agree that some patients will require combination therapies while others will succeed with monotherapies. This will be linked with disease severity.
There are more observations here and a raft of supporting data points and arguments. We lack sufficient space to cover all these in this summary, so read and enjoy yourself!
Louise Campbell convenes liver nursing and nurse educator experts Kathryn Jack, Michele Clayton, Pam O'Donoghue and Patrizia Kunzler to consider where liver nurses and advanced nursing practitioners should fit into treatment and communication paradigms and what support they will need. Stephen Harrison joined to offer a different viewpoint.
This conversation explores the need for and value of patient education in the NASH Patient Care process. It starts with almost a tangential request that some of the money budgeted for expensive systemic HCC therapies in the UK be rededicated to patient education earlier in the treatment process.
From there, the conversation shifts to consider the value of the need for early-stage treatment strategies in poorer countries that are never likely to be able to afford the expense of drugs or treatment modalities. In the end, each panelist describes a change she would like to see in the next 2-3 years.
Surfers Louise Campbell and Jörn Schattenberg are joined by patient advocate Robert Mitchell-Thain, liver nurse Michelle Clayton, and healthcare consultant Stephen Callaghan to talk about their unique perspectives in the process of pathway development for NAFLD. In doing so, the group looks for ways to incorporate the 17 Sustainable Development Goals (SDG) established by the United Nations - an urgent call for action on health, economy, and starvation amongst other human rights issues.
This final conversation of Season 3 - Episode 42 discusses the power of education to place liver disease on a higher agenda. Louise notes that liver health is not engaged with at a school level. She suggests that liver health as an outcome be incorporated from an earlier age. This familiarity could fundamentally assist the more ‘generalist’ approach that Stephen promotes. Michelle mentions potential pushback and the group revisit the need for more patient resources. Beyond access to affordable nutrition, communities need safe spaces and opportunities for exercise.
Next, the group expresses their eagerness for building an inclusive, robust framework for a NAFLD pathway. Michelle reiterates her position that the success of such a framework requires the contributions of nurses and allied health professionals. Robert also hopes to see uniform action on this pathway to tap into an immense knowledge base. Stephen enjoyed his first podcast feature and is looking to translate successful strategies from previous pathways to the liver space. Jörn is appreciative of joining this conversation on inclusion, placing a great value on honest and open feedback.
Surfers Louise Campbell and Jörn Schattenberg are joined by patient advocate Robert Mitchell-Thain, liver nurse Michelle Clayton, and healthcare consultant Stephen Callaghan to talk about their unique perspectives in the process of pathway development for NAFLD.
Louise begins this conversation by asking Stephen about a successful HIV pathway that he had contributed to, and how it may be applicable to liver disease. Stephen maintains that “it’s about identifying the most important measures across a pathway.” A pathway can be measured both stepwise and incrementally by indicators within the larger framework. Stephen provides an example of application through the aforementioned HIV pathway. Next, Robert explores the gamification of digital health, and what that may provide in terms of patient empowerment. This movement appeals to Jörn because it can help define goals. Both patients and health professionals are working under mutual motivators.
Surfers Louise Campbell and Jörn Schattenberg are joined by patient advocate Robert Mitchell-Thain, liver nurse Michelle Clayton, and healthcare consultant Stephen Callaghan to talk about their unique perspectives in the process of pathway development for NAFLD. In doing so, the group looks for ways to incorporate the 17 Sustainable Development Goals (SDG) established by the United Nations - an urgent call for action on health, economy, and starvation amongst other human rights issues.
This conversation begins by discussing the role of patients in the scope of allied health. Louise prompts the question, where do they fit into the pathway? Robert identifies the many touch points and opportunities presented for patient inclusion. He also suggests that patients tend to communicate in terms of quality of life issues - not in the language of diagnostic scores. Michelle joins to highlight the importance of nurses and allied health professionals in the context of patient interactions. Nurses and allied health professionals can offer conversational insights that promote liver health. However, Jörn expresses the shared concern that a lack of funding tends to stretch nursing resources thin.
The discussion shifts to promoting liver health in a wider professional setting. Stephen speaks to the reality that “everyone is fighting their own corner” in advocacy and diagnostics. The group then explores ways by which more generalist testing can identify and capture at-risk patients earlier in the pathway. Patients presenting comorbidities need more than one therapy, more than one organ monitored, and more than one answer to their questions.
Surfers Louise Campbell and Jörn Schattenberg are joined by patient advocate Robert Mitchell-Thain, liver nurse Michelle Clayton, and healthcare consultant Stephen Callaghan to talk about their unique perspectives in the process of pathway development for NAFLD. In doing so, the group looks for ways to incorporate the 17 Sustainable Development Goals (SDG) established by the United Nations - an urgent call for action on health, economy, and starvation amongst other human rights issues.
Earlier this year, Jörn co-authored a paper titled, A sustainable development goal framework to guide multisectoral action on NAFLD through a societal approach (2022). Jörn talks about the process and intention behind the paper. He recalls that leading author, Jeff Lazarus, sought to incorporate the SDG and its applicable targets to the challenges posed specifically by NAFLD. The group identifies a lack of representation in authorship and discusses how to improve on this. It is agreed that developing a pathway requires the contribution of nurses, patients and patient advocates, and other allied health professionals.
Surfers Louise Campbell and Jörn Schattenberg are joined by patient advocate Robert Mitchell-Thain, liver nurse Michelle Clayton, and healthcare consultant Stephen Callaghan to talk about their unique perspectives in the process of pathway development for NAFLD. In doing so, the group looks for ways to incorporate the 17 Sustainable Development Goals (SDG) established by the United Nations - an urgent call for action on health, economy, and starvation amongst other human rights issues.
Earlier this year, Jörn co-authored a paper titled, A sustainable development goal framework to guide multisectoral action on NAFLD through a societal approach (2022). Louise begins by asking Jörn about the process and intention behind the paper, and how it champions the SDG. Jörn recalls that leading author, Jeff Lazarus, sought to incorporate the SDG and its applicable targets to the challenges posed specifically by NAFLD. The paper is formulated by consensus using The Delphi Process, whereby two rounds of interdisciplinary discussion decided on 16 deliverable targets relevant to NAFLD. It aims to determine what is important to be addressed by politics and those involved with research funding.
Michelle notes this paper is absent of nurses, patient advocates or other allied professional contributors. Robert joins to reframe Michelle’s concerns, asking how do we do it better next time? He seeks a more genuine multisectoral representation in what could only then be dubbed as a truly societal approach. Jörn acknowledges these shortcomings and agrees that, as the paper stands, it can be seen as a physician’s viewpoint. Louise reckons that the paper serves a foundation and that if it were to be further developed, now is the time to introduce different perspectives.
The conversation turns to the next steps of establishing such a framework. Stephen Callaghan provides an anecdote from his time contributing to the development of a pathway for HIV. The driving message is that not every stakeholder comes from a clinical environment. As such, the group agrees that herein lies the importance of communication. Robert states that most patients are relating in terms of describing symptoms and other quality of life issues. Some of the more complex metrics understood by specialists may not translate outside of the professional circle. Michelle then highlights the critical role of nurses positioned as a more conversational contact with the ability to identify risk factors and promote liver health. Both points resonate with Jörn. He explains that the SDG paper emphasizes a need for funding for nurses. He also shares Robert’s concern surrounding the power gap that can negatively impact the patient’s ability to contribute pathway development.
Next, Stephen speaks to the reality that “everyone is fighting their own corner” in advocacy and diagnostics. Robert relates, stating the matter is complex and that the community should come together to offer more than one answer to patient questions. Jörn alludes to Stephen’s position as a generalist to combat this issue. The conversation then shifts to education. Louise notes that liver health is not engaged with at a school level. She suggests that liver health as an outcome be incorporated from an earlier age. This familiarity could fundamentally assist the more ‘generalist’ approach. Michelle mentions potential pushback and the group revisit the need for more patient resources. Beyond access to affordable nutrition, communities require safe spaces and opportunities for exercise.
Final thoughts are shared and each expresses their eagerness for building an inclusive, robust framework. The success of such a framework requires many players, and Stephen hopes to translate strategies from past successful pathways to place liver disease on a higher agenda.
Jörn speaks about co-authoring an article, “The Nonalcoholic Steatohepatitis (NASH) drug development graveyard: established hurdles and planning for future successes.” In doing so, he discusses areas for improvement he feels clinical trial strategy and design will require. Joining the conversation is Stephen Harrison and Global Liver Institute Founder and CEO, Donna Cryer. Both Stephen and Donna approach the conversation from the patient and patient advocate perspectives.
This episode From the Vault provides an amazing and complementary comparison to how far this topic has come in just two years. Notably, much has developed in the space of NITs since this paper in 2020. In this week's Surf, Season 3 - Episode 41, Roger, Louise, Stephan and Jörn reflect on what has improved in the intervening time period, what has not, and where this space is headed.
THE NASH Tsunami audience came to know Jörn Schattenberg in the Fall of 2020 when he shared a paper he had recently co-authored on why NASH drug trials failed. This week, the same group that discussed that paper – Jörn, Stephen Harrison, Louise Campbell and Roger Green – reflect on what has improved in the intervening time period and what has not. The group speculates what can still be accomplished.
This conversation begins with Roger suggesting that tertiary care research universities that have their own primary practice be utilized as an accessible point of referral. The group agrees that while a good idea, this may not translate to the European system.
Roger poses the closing question: what is there to look forward to in the space of NASH clinical trials and improving screen fail rates in the next 6 months to a year? Louise is looking for the approval of FibroScan for primary care in the UK. Jörn is hoping for an opportunity to offer health care services through referral systems. Stephen talks about getting a drug approved. In response to the latter, Roger finishes with a Stephen quote: is the juice worth the squeeze? This "juice" takes forms of cash and optimism, and it will be worth the squeeze if a drug sees successful development.
THE NASH Tsunami audience came to know Jörn Schattenberg in the Fall of 2020 when he shared a paper he had recently co-authored on why NASH drug trials failed. This week, the same group that discussed that paper – Jörn, Stephen Harrison, Louise Campbell and Roger Green – reflect on what has improved in the intervening time period and what has not. The group suggest that researchers are making progress in reducing screen fail rates, but not in the critical issues of accessibility and equity.
In this excerpt, Jörn asks whether these new, more focused approaches might lead to investigators overfitting patients. The positive of this outcome, he notes, is that sweet spot patients will be in a position to respond to drug. Louise takes on an additional issue: what is the affect of patient lifestyle mitigation on these trials. Her concern: patients who work hard enough to improve their liver condition after learning they have the disease may be so successful that they no longer qualify by the time they would be called for biopsy.
The conversation strays into discussing the high value of bring artificial intelligence assists into histopathological interpretation before Stephen returns to the question of recruiting more patients. He notes that the goal is not merely to pull more patients into the first stages o recruitment ("the top of the funnel") but to improve our distribution of different kinds of minorities and subpopulations with high rates of NASH. He points out the fallacy of treating only mainstream Caucasian Americans and assuming results of these trials will hold true for everyone given what we now know about the important of genotyping and mutations tied to race or ethnicity.
As this conversation ends, Stephen outlines potential solutions based on shifting recruitment out of brick-and-mortar trial sites and to recruiting and testing at primary care offices or even patients' homes.
THE NASH Tsunami audience came to know Jörn Schattenberg in the Fall of 2020 when he shared a paper he had recently co-authored on why NASH drug trials failed. This week, the same group that discussed that paper – Jörn, Stephen Harrison, Louise Campbell and Roger Green – reflect on what has improved in the intervening time period and what has not. Large metropolises are identified as missed opportunities.
Stephen starts this conversation by shifting focus from issues surrounding trial criteria to the challenge of finding the right patients for these trials. He notes that of the millions of patients with NASH in the U.S. today, only a small fraction might ever realistically find their way to a NASH trial. The biggest factor is that they can only find their way to a trial if they live with clear access to a trial center. This is not simply a question of rural and exurban residents having too far to travel. He cites Chicago as a city that contributes minimal patient enrollment, despite being a large cites whose population suffers from high levels of metabolic disease.
Jörn adds that while we might believe that European countries with more socialized, government-centered systems would not exhibit this maldistribution in where trial patients live, that belief would be wrong. Roger suggests that the U.S. system, with its highest levels of investment in medical technologies and broader distribution of care sites, might actually be better equipped to attack this issue.
At that point, Roger returns to an earlier comment to ask Stephen addresses how mid-trial reassessment of screening criteria works and why it improves screen fail rates. Stephen's answer takes up the rest of this conversation.
THE NASH Tsunami audience came to know Jörn Schattenberg in the Fall of 2020 when he shared a paper he had recently co-authored on why NASH drug trials failed. This week, the same group that discussed that paper – Jörn, Stephen Harrison, Louise Campbell and Roger Green – reflect on what has improved in the intervening time period and what has not. The group suggest that while non-invasive techniques (NITs) have made a significant contribution to patient enrolment, there remains reliant on additional screening methods.
This conversation opens with Jörn's observation that NITs are not always part of the protocol when assessing patients for their inclusion or exclusion in clinical trials. However, he states, experienced researchers will rely on these tools along with presence or absence of other metabolic diseases to decide which patients should not progress to biopsy due to high likelihood of screening out of the study anyway. Stephen concurs, adding that by considering these other risk factors, the clinical trials benefit from a more enriched patient population. and fewer unnecessary biopsies.
From here, Stephen goes on to discuss two other pivotal issues: advance in strategies for reading biopsies and the impact of high screen fail rates on staff morale. On the first point, he states that good drugs have been lost in development because the strategy for reading biopsies, which relied on a single pathologist to read, created interpretative barriers that led to trials failing or being discontinued. This has led to a place today where all trial design incorporate consensus histopathology reads. On the second, he contrast staff performance for two studies on the same drug: an obesity study with a 25% screen fail rate and a NASH study with an 80% rate. He describes the palpable difference how staff feels about working on each of these projects.
As the conversation ends, Louise comments on changing FibroScan thresholds for admission to some trials and Stephen describes how inclusion thresholds might vary from trial to trial and ways he uses other NITs to complete his assessments.
THE NASH Tsunami audience came to know Jörn Schattenberg in the Fall of 2020 when he shared a paper he had recently co-authored on why NASH drug trials failed. This week, the same group that discussed that paper – Jörn, Stephen Harrison, Louise Campbell and Roger Green – reflect on what has improved in the intervening time period and what has not.
After Roger Green sets the stage for this conversation, Jörn reflects back on the 2020 paper he co-authored with Joost Drenth and considers important changes in patient screening since then. In his own words, “The way we use biomarkers and AI to augment outcomes has changed the field dramatically.” Whereas biopsy used to be the core method used to recruit patients, Jörn notes that many practitioners now rely on NITs to assess the patient's likelihood of screening into a trial before conducting a biopsy. The result is a significant reduction in non-essential biopsies.
Stephen follows Jörn by discussing ways his own practice has benefitted greatly from the developing a prescreen strategy that relies heavily on NITs. Instead of doing "five biopsies a day, maybe 25 or 30 a week," he now starts with FAST scores and cT1 and, if these seem promising, moves to multiparametric MRI before deciding who to biopsy. Specifically, his practice is now able to utilize VCTE (FibroScan) and other NITs to mine data in real time and refer patients to the proper clinical trial as a result.
As the episode winds down, Stephen alludes to the idea of "mid-trial corrections" in pre-biopsy NIT screening criteria and advances in how biopsies are read in trials today as other areas where procedure has improved markedly.
THE NASH Tsunami audience came to know Jörn Schattenberg in the Fall of 2020 when he shared a paper he had recently co-authored on why NASH drug trials failed. This week, the same group that discussed that paper – Jörn, Stephen Harrison, Louise Campbell and Roger Green – discuss what has improved in the intervening time period and what has not. The group suggest that researchers are making progress in reducing screen fail rates, but not in the critical issues of accessibility and equity.
As the conversation begins, Jörn harkens back to the 2020 paper and reflects on improvements in cost-effectiveness and duration of the trial process since. “The way we use biomarkers and AI to augment outcomes has changed the field dramatically.” Yet clinical trials are still reliant on the same endpoint. A surrogate is required for conditional drug approval. Roger asks for the most important improvements that have resulted from conversations around patient selection for a trial. Jörn recalls the past reliance on biopsies and compares today’s focus on non-invasive techniques (NITs).
Stephen joins to highlight improvements in the way practices utilize VCTE (FibroScan) and other NITs to mine data in real time and refer patients to the proper clinical trial. One idea Stephen mentions: evaluating NIT values during the recruiting process to reset cutoff levels. He also discusses expanding screening criteria to include non-hepatic metabolic risk factors such as obesity and diabetes. Both approaches to patient refinement are contributing to more successful studies and limiting unnecessary biopsies. With fewer screen failures, sites remain engaged. Louise Campbell agrees that mitigating screen fail rate is key to fighting study fatigue.
The conversation shifts to finding patients for these trials. Stephen notes that major metropolises still do not have access to NASH clinical trials. "We’re putting almost zero NASH patients in clinical trials out of a city as large as Chicago that has high rates of obesity, diabetes and metabolic syndrome.” NITs like the FibroScan are unavailable in large swaths of the country. Even where they are available, a lack of education around NASH diagnostics tests remains a barrier. Jörn adds that multiple hurdles prevent patients from accessing NASH trials in socialized healthcare systems. Roger believes the US system may have a better shot than Europe at broadening recruitment processes because the technology developed under larger U.S. budgets means that some pivotal technologies are more widely available.
Next, Roger comments that for as long as screen fail rate has been discussed on this podcast, we had never discussed the idea of mid-trial adjustments. Stephen gives an example of adjusting FibroScan thresholds mid-trial to boost the number of eligible patients. Jörn shares his belief that use of NITs outside the formal qualification criteria has helped reduce screen fail rates.
Stephen shifts focus to a bigger issue: equity in representation of underserved patients in these trials. There is an issue of decentralized trials, whereby at-risk groups are under-referred due to several factors. Stephen outlines potential solutions. Roger suggests tertiary care research universities that have their own primary practice as suitable to become an accessible point of referral. He notes this may not translate to the European system and Louise agrees.
What is there to look forward to in this space in 6 months to a year? Louise is looking for the approval of FibroScan for primary care in the UK. Jörn is hoping for an opportunity to offer health care services through referral systems. Stephen says we’ll hopefully be a step closer to getting a drug approved. Roger finishes with a Stephen quote: is the juice worth the squeeze? The juice takes forms in cash and optimism, and the juice will be worth the squeeze if a drug sees successful development.
Episode 40 focuses on lean NASH, and Michelle Long notes that many patients with lean NASH are diagnosed in the Emergency Department when they present with symptoms of decompensating cirrhosis. This conversation from November 2021 considers cirrhotic patients from a different perspective: their uniquely valuable role in clinical trial strategy as the world evolves beyond biopsy as gold standard.
Mazen Noureddin notes during this week's episode that when he identifies lean NASH patients, he encourages them strongly to participate in clinical trials. This conversation also looks at the value of cirrhosis studies in clinical trial design, although from a quite different perspective.
From the initial description of this conversation: In this conversation, Stephen Harrison starts by pointing out that non-cirrhotic NASH trials and NASH cirrhosis trials differ significantly in goals, endpoints and patient severity. From there, he dives into the NASH cirrhosis trial group with his review of REVERSE, which Vlad Ratziu presented at AASLD. Jörn Schattenberg and Mazen Noureddin also comment on design of this trial. The conversation focuses on two issues: who is the optimal patient for a NASH cirrhosis trial and what is the most appropriate attainable endpoint and, therefore, clinical design? On the optimal patient issue, the group agrees the ideal patient is a well-compensated cirrhotic, because the presence of portal hypertension makes the entire healing issue so much more complex. There was less agreement on the optimal design question.
As the NASH pandemic grows in the number and diversity of patient cases, one patient group receiving increased notice includes patients with "lean NASH," those with "normal" BMI levels (BMI<23 for Asians; BMI<25 for other racial groups). Last month, Gastroenterology published Best Practice recommendations for diagnosing and treating lean NASH. In this conversation, co-authors, Drs. Michelle Long and Mazen Noureddin join Louise Campbell and Roger Green to discuss Best Practice #6, which focuses on alcohol screening with lean NASH and really ANY patient who might have Fatty Liver disease.
This conversation starts with Louise Campbell pointing to Best Practice #6, querying patients routinely regarding levels of alcohol consumption. She points out that many patients will not provide an honest answer. Mazen points out that, unlike obese patients, with lean patients, the physician has to check every realistic alternative to lean NASH, and alcohol is certainly one of these. He agrees that patients might not always provide accurate answers. The conversation follows along on the challenges of alcohol questioning until Roger asks the final question. You need to listen to this conversation to hear what the various panelist had to say.
As the NASH pandemic grows in the number and diversity of patient cases, one patient group receiving increased notice includes patients with "lean NASH," those with "normal" BMI levels (BMI<23 for Asians; BMI<25 for other racial groups). Last month, Gastroenterology published Best Practice recommendations for diagnosing and treating lean NASH. In this conversation, co-authors, Drs. Michelle Long and Mazen Noureddin join Louise Campbell and Roger Green to discuss why early diagnosis is so important for patients with lean NASH, which has a subtly different focus than other forms of NASH.
This conversation harkens back to the previous week (Season 3, Episode 39) and Ian Rowe's analysis of different early diagnostic techniques and assessment that "Fibrosis First" was the most cost-effective and highly effective way to identify patients at risk. Roger points out that Fibrosis First looks very similar to what Mazen and Michelle recommend here. For this population, he asks how to identify lean patients that need this kind of workup.
Mazen states that the key marker is an extremely high ALT level (40 or 50 would not create this level of scrutiny, but 80 or 90 would.) Michelle agrees, but adds that most patients are diagnosed when they appear with some level of decompensating cirrhosis. As a result, she suggests that a primary care physician probably does not need to evaluate any patient they would not already consider at high risk: Type 2 diabetes or very high ALT levels. She also indicates that "Fibrosis First" sounds like an intriguing approach and that she needs to find Ian's poster or hear the podcast.
Michelle also comments that primary care physicians might be uncomfortable or intimidated screening for cirrhosis, which they do not feel qualified to treat. Louise asks whether they might be more comfortable assessing liver health vs. screening for cirrhosis.
Roger asks what else a hepatologist might take out of this paper. Michelle repeats their strong call for more research with this population, while Mazen points to Table Two in the publication as a comprehensive list of the various other conditions physicians need to screen for. Further, he notes that by placing the entire diagnostic pathway in a single chart, he empowers a hepatologist or gastroenterologist to approach primary care physicians and delineate which parts of the algorithm are the domain of which specialty. (The chart color codes this issue, with the pre-specialist elements in blue and hepatgologist elements in green.)
Finally, Mazen points out that when he sees lean NASH patients, he tries to place them in clinical trials, which can benefit the individual patient and generally advance our understanding of how to treat this condition.
As the NASH pandemic grows in the number and diversity of patient cases, one patient group receiving increased notice includes patients with "lean NASH," those with "normal" BMI levels (BMI<23 for Asians; BMI<25 for other racial groups). Last month, Gastroenterology published Best Practice recommendations for diagnosing and treating lean NASH. In this conversation, co-authors, Drs. Michelle Long and Mazen Noureddin join Louise Campbell and Roger Green to discuss the development of the one-page algorithm that lies at the heart of this publication.
This conversation starts with Mazen Noureddin pointing out specific elements of the algorithm "that we're proud of." He notes that they start by identifying two specific patient groups they chose to focus on based in part on cost-effectiveness analysis: patients with Type 2 Diabetes and patients over age 40. They rely on the dominant diagnostic paths, which they recommend following with FibroScan. They recommend confirming the diagnosis with MRI or biopsy if there is any doubt. Most important, they pull all this information into a one-page algorithm that incorporates recommendations for primary care or endocrinology (pre-diagnosis) with hepatologists (post-diagnosis for patients with NASH and Fibrosis Level 2 or higher). They also discuss other tests of more recent development: MAST, FAST, MEFIB, cT1 and other multi-parametric measures.
Louise compliments the publication for its simplicity and clarity. She also notes approvingly that it recommends repeat testing every 6 months to two years, depending on the level of fibrosis. This is a more frequent schedule than the 3-5 years most commonly recommended by other algorithms. She likes not only the increased frequency but also the stratification of test frequency based on the level of risk.
Michelle agrees strongly. She notes that with a 3-5 year follow-up recommendation, many patients will be lost to follow-up. Mazen goes on to note that with T2D patients, physicians check annually for eye, kidney or neurological complications. He asks why FIB-4 should not be added to that list. Louise identifies another benefit: patients are more likely to realize when they have not had their annual tests, whereas they are less likely to recall after a three-year gap. The rest of the conversation centers around reasons that a 6-12 month recommendation makes more sense while requiring little additional time or spending. When Roger suggests that a rationale for 3-5 year testing might be so that payers are not concerned about the likely downstream costs, Mazen notes that based on his research and assessment, annual will be cost effective.
As the NASH pandemic grows in the number and diversity of patient cases, one patient group receiving increased notice includes patients with "lean NASH," those with "normal" BMI levels (BMI<23 for Asians; BMI<25 for other racial groups). Last month, Gastroenterology published Best Practice recommendations for diagnosing and treating lean NASH. In this conversation, co-authors, Drs. Michelle Long and Mazen Noureddin join Louise Campbell and Roger Green to discuss how they came to undertake this assignment and to organize their thoughts.
The conversation starts with Mazen Noureddin discussing why he, Michelle and Joseph Lim wrote this paper (in his simple description, "we are asked for it," which, he notes, "we were quite excited about.") From there, Mazen and Michelle describe the actual process of organizing the article. First, they needed to align on a single definition of "lean" (they settled on BMI<23 for Asians and BMI<25 for other racial groups.) From there, they relied on clinical experience to develop a basic list of 15 best practice elements. These served as a foundation for their work. From there, they conducted an extensive literature review to clarify each element.
In response to a question from Roger, Mazen comments that there were few surprises in what they found, if any, largely because the work came from the co-authors' extensive clinical experience. Mazen talks about an experience with two Indian brothers to explain how straightforward the process can be, and also how detailed. They note that lean NASH is harder to diagnose and requires painstaking efforts to rule out more obscure diagnoses that might not come into play with overweight or obese steatohepatitis patients. As Mazen notes, "there is some art" in treating these patients.
Michelle shifts focus to the tables and charts they put together for the article. Her point: physicians are too busy to dive into the issues and possibilities the way the co-authors did. This made it important to provide clear, concise guidance with relevant data in a small number of charts and tables and a stepwise approach.
Louise Campbell joins the conversation to compliment the authors and comment on the clear synergy between these best practices and approaches for diagnosing non-lean patients. She then asks whether there are differences between different Asian populations. The conversation ends with Michelle stating that insufficient research on this issue exists and Mazen, while agreeing, noting that the relied on publications from India and other parts of Asia in building their practices.
As the NASH pandemic grows in the number and diversity of patient cases, one patient group receiving increased notice includes patients with "lean NASH," those whose BMI levels are "normal." Last month, Gastroenterology published Best Practice recommendations for diagnosing and treating lean NASH. Two of the authors, Drs. Michelle Long and Mazen Noureddin, were good enough to come on the podcast to share the thinking behind this article along with its key observations and recommendations.
This conversation starts with Roger Green asking Michelle and Mazen how they came to write this piece and how the paper came together working with co-author, Dr. Joseph Lim. First, as Michelle notes, "we had to all get on the same page," on the issue of the highest BMI that would be considered lean or, more precisely, not overweight. From there, the team outlined 15 Best Practices based on clinical experience, and set out to refine these based on relevant literature and recommendations from colleagues and reviewers. The co-authors note that while little of what they learned while preparing this paper was surprising, it forced them to focus on creating a fairly simple set of stepwise goals for clinicians to follow. Louise Campbell joins the conversation to praise the simplicity and clarity of the Best Practices chart the co-authors created.
After noting that this algorithm is not very different from others, Mazen goes on to mention "a couple of things...that we're proud of:" identification of high-risk patients based on age (over 40) or presence of Type 2 diabetes. He also notes that they provided greater clarity around more advanced non-invasive tests like ELF, MAST, FAST, MEFIB, MRI, and cT1.
The conversation shifts to focus on the recommendation to retest every 6 or 12 months. Louise notes this approvingly. The group agrees that screening T2D patients annually using FIB-4 is not very different than screening annually for eye, kidney or neurological complications. Roger Green joins the conversation to suggest a 3-5 year follow-up recommendation is not patient-centric, but might calm payers concerned about skyrocketing costs of treating Fatty Liver disease. Mazen shares his expectation that yearly evaluation will be cost-effective and patient-centric. Roger shares an informal belief he has developed that whether due to later stage diagnoses or different disease pathogenesis, lean NASH patients might be more costly because patients progress to cirrhosis more quickly after the original diagnosis. Michelle tends to agree but notes that more research is needed on this.
Next, the conversation shifts toward diagnostic approaches. Roger mentions the possible benefit of the "Fibrosis First" method that Ian Rowe discussed the previous week (S3, E39), particularly appropriate when primary care providers observe danger signs in lean patients. Mazen points to extremely elevated liver enzyme levels (ALT of 80 or 90). Michelle agrees, but notes that most of her lean NASH patients are diagnosed in an ED with complications of cirrhosis. The group then spends time asking what might make primary care providers comfortable testing for fibrosis, even if only to pass the patient on to the appropriate specialist.
Roger asks what different groups can learn from this paper. Michelle states that this is a clear call for more research. Mazen points to Table 2 in the paper, which lists other diseases that hepatologists should consider when evaluating these patients. He continues to state that the document is helpful for non-hepatologists and hepatologists alike. Finally, he points out that clinical trials are pivotal for these patients.
The last several moments focus on how to ask patients about alcohol consumption and then the closing question. Michelle notes the importance of using lists and tables in the paper to guide the special issues in treating these patients.
This week's "Conversation from the Vault" comes from September 2021, when Anthony Villiotti of NASH kNOWledge joined Louise Campbell and Roger Green to discuss what he considered the "biggest Fatty Liver story of the summer."
In his answer, Tony pointed to two studies published during the summer. The San Antonio Military Medical Center study confirmed work done a decade earlier that suggested overall NAFLD and NASH incidence in a population of asymptomatic middle-aged Texans (37% NAFLD and 14% NASH) might be far higher than the most common publicly quoted numbers (25% and 5,6%, respectively). As we wrote in our conversation synopsis at the time, "Tony and Louise Campbell agree on the importance of educating children starting in their early years of schooling. Tony also comments on his belief in grass-roots education and hopes that as the COVID-19 pandemic abates, he will have more opportunities to do so. Louise talks about the need to educate/motiave primary care practitioners and related specialists to test more frequently and learn about the role the liver plays in non-communicable metabolic diseases they treat more frequently."
One of the most important challenges facing Fatty Liver stakeholders involves improving early diagnosis for patients with clinically relevant or advanced fibrosis (F2/3). Today, a significant percentage of patients learn they are living with cirrhosis in the Emergency Department during a decompensating event. Four in ten of these patients in the UK do not leave the hospital. Episode 39 reviewed a model that Ian Rowe and Richard Parker developed to determine the most cost-effective strategy for F2/3 diagnosis.
As this conversation starts, Louise Campbell notes that John Dillon reported in Barcelona that slightly over half of patients identified as having Fatt Liver via iLFT never returned for their appointments. Ian Rowe points out that this will reduce the costs in the model due to missed diagnoses but questions whether this cost reduction is truly beneficial since missed patient visits translate into non-treatment. More important, he reminds us that iLFT is under constant improvement so that data collected earlier in its lifecycle might not accurately reflect its costs and benefits today.
Upon Roger Green's invitation for other questions Louise Campbell asks whether "we" (presumably the UK NHS) should do a better job supporting positive diet and exercise activity for healthcare professionals inside the system. On a more serious note, this leads Ian and Louise to focus on the policy issues that can support patients better (particularly those in the workforce). Ian points out that alcohol is issue #1 for many of these patients. He and Louise go on to point out the importance of public policy around things like soda and sweet food advertising in shifting consumers' focus or craving for bad foods. Roger suggests that this is a two-element issue: stopping advertising for soda and sweets will reduce disease over time but we also need to treat patients who already have developed disease. As he puts it, policy can "put your foot on the hose," but even if we stop the in-flow of new Fatty Liver and metabolic patients, we still have "the patients in the hose" and they will need therapy.
As a final thought before wrap-up, Ian shares his belief (which Louise also holds) that VCTE might be more effective in causing changes in patient behavior than blood tests, even if they point up the exact same patient need. The difference: feedback from VCTE comes in real-time where patients get face-to-face feedback and respond, whereas bloodwork results comeback to the patient several days later and delivered impersonally.
From here, the group moves to the wrap-up question, which addresses research we should be doing and action steps/changes in behavior we should be promoting. You will have to listen for yourself to hear Surfers' answers.
One of the most important challenges facing Fatty Liver stakeholders involves improving early diagnosis for patients with clinically relevant or advanced fibrosis (F2/3). Today, a significant percentage of patients learn they are living with cirrhosis in the Emergency Department during a decompensating event. Four in ten of these patients in the UK do not leave the hospital. Episode 39 reviewed a model that Ian Rowe and Richard Parker developed to determine the most cost-effective strategy for F2/3 diagnosis.
This conversation centers around challenges related to early diagnosis and NASH Patient Management. As Roger Green notes, listeners to NASH Tsunami might recall a significant number of conversations in which patients and advocates complain about doctors telling them "not to worry" about their Fatty Livers for years until the condition progresses to cirrhosis. Louise Campbell focuses on a different challenge: that of NASH patient management when patients are dealing with other metabolic diseases that are better known or where approved treatments exist.
One of the most important challenges facing Fatty Liver stakeholders involves improving early diagnosis for patients with clinically relevant or advanced fibrosis (F2/3). Today, a significant percentage of patients learn they are living with cirrhosis in the Emergency Department during a decompensating event. Four in ten of these patients in the UK do not leave the hospital. Episode 39 reviewed a model that Ian Rowe and Richard Parker developed to determine the most cost-effective strategy for F2/3 diagnosis.
This conversation starts with Louise Campbell agreeing with the vision that led Ian and Richard to build this model. She notes recent data she heard that 85% of all US patients with cirrhosis (and 55% in the UK) learn their diagnoses for the first time in an Emergency Department, which suggests the need to improve earlier diagnosis. She notes that some UK programs are widely cited as examples of good (or best) practice, but, more important, notes that these have been cited as examples for a long time, but also notes that other regions and hospitals have not emulated them.
She goes on to ask how the efficiency and number of patients captured in the model would increase if the target expanded to include all patients with metabolic disease. Ian notes that these patients were not included in the model and also suggests that the question reflects a larger question about the goal of this kind of screening.
One of the most important challenges facing Fatty Liver stakeholders involves improving early diagnosis for patients with clinically relevant or advanced fibrosis (F2/3). Today, a significant percentage of patients learn they are living with cirrhosis in the Emergency Department during a decompensating event. Four in ten of these patients in the UK do not leave the hospital. Episode 39 reviewed a model that Ian Rowe and Richard Parker developed to determine the most cost-effective strategy for F2/3 diagnosis.
In this conversation, Ian Rowe describes the factors that motivated him and Richard Parker to build a decision model focusing on early NASH diagnosis. He identifies three data points demonstrating how severely NASH stakeholders need a better early diagnosis paradigm and then describes the five diagnostic strategies his model will test. :
- the high percentage of people whose liver disease is picked up for the first time when they present in the ED with decompensating disease or hepatic encephalopathy
- the fact that roughly four in ten of these patients will die during treatment for this initial round of liver disease
- the inefficiencies around diagnostic current methods, whereby practitioners flag abnormal liver enzyme tests and refer to specialists, where it may take months to get a specialist appointment.
He then describes the five early diagnostic strategies that will be tested and contrasted in this decision curve model.
One serious challenge in the overall management of Fatty Liver disease involves creating cost-effective methods for "early" diagnosis. The term "early" is relative because, as Ian Rowe puts it, a "substantial proportion" of people admitted to hospital with various symptoms of decompensating cirrhosis or hepatic encephalopathy never received a diagnosis of advanced liver disease before they presented. Simply diagnosing these patients during advanced fibrosis (F2 or F3) can save lives, improve longevity and quality of life for these patients and save money for healthcare systems, all at the same time.
Ian spends the first ten minutes of this episode describing a model he and Richard Parker developed to evaluate five diagnostic strategies:
- Targeted -- simple non-invasive liver screening
- Targeted + risk stratification -- targeted assessment plus FIB-4 or VCTE (FibroScan) for patients believed to be at high risk
- iLFT -- automated assessment of abnormal LFTs analyzed with other systemic measures in a medical record system
- "Comprehensive" -- a "kitchen sink" approach that runs iLFT analysis and conducts FIB-4 +/- VCTE on every patient
- "Fibrosis first" -- an approach that deploys viroserological and iron testing plus FIB-4 +/- VCTE for every patient
"Fibrosis first" scored best in cost effectiveness (cost per correct diagnosis of treatable liver disease) and "decision curve analysis", which looks at true positive outcomes and false positive outcomes, correctly identifying 85% of treatable liver disease patients (vs. 90% for the comprehensive approach and less than 15% for the current targeted approach.) Fibrosis first has the added benefit of not progressing treatment for people who may have steatosis without fibrosis.
The rest of the conversation entails Ian, Louise Campbell and Roger Green sharing questions and observations. Highlights:
- Louise agrees that the current targeted pathway approaches do not work and identifies lack of access to advanced testing in primary care as a central issue. She asks how many additional patients with Type 2 Diabetes, other metabolic diseases or CVD could be identified through this approach. Ian cannot answer because the question is outside the scope of the research. He points out that to assess different approaches accurately, researchers and policymakers need to settle on whether the goal is to identify steatohepatitis or something broader.
- Louise asks about the frequency and nature of referrals. Ian notes that one issue with iLFT is a high level of referrals for conditions that might not require treatment, the most common of which is "abnormal LFT without fibrosis."
- Roger notes that iLFT might help patients who complain they never heard about their NASH earlier. He also recalls Quentin Anstee and Stephen Harrison discussing recently that FIB-4 can serve as a prognostic measure not only for liver-related deaths, but also CV deaths and all-cause mortality.
- Louise suggests that patients will do better if they adopt a behavior belief model instead of a sick patient approach and that the earlier in disease we intervene, the more success we will have. Roger and Ian note that Louise's focus is broader in scope than his model. Ian further notes that we do not know when non-fibrotic patients should be tested again, although he has some thoughts about this.
- Louise notes that one element that might make iLFT costly is that only 45% of patients picked up on iLFT are referred into the model. Ian notes that this insight might require changes in the model.
As the conversation winds down, it shifts toward policy issues: should we focus testing on the workforce (Louise) and it the best point of intervention to limit advertising of unhealthy foods (Ian).
Our week of "Greatest Hits" episodes from the vault concludes with this conversation from the episode discussing the inaugural Innovations in Clinical Care - Barcelona (or INCBCN) conference that convened this past May. This conversation reviews two controversies about the meaning of patient empowerment that arose at the conference.
One key event that 2022 witnessed was the inception of the Innovations in NAFLD Care series, a global effort to discuss clinical care pathways and patient treatment processes in a systematic way. Surfing the NASH Tsunami is a media partner and advocate for this series.
This conversation comes from our review of the conference. The discussion itself is triggered by Roger Green's question about controversies at INCBCN 2022 and addresses two issues. The first is the ongoing controversy over what to call the disease itself. The second addresses the concept of biohacking, which either empowers patients by providing them with extensive data for self-management or disempowers them by divorcing the individual patient's interpretation of this data from disease understanding.
Our week of "Greatest Hits" episodes from the vault continues with this conversation from the episode discussing systematic failures of NAS scoring due to inconsistencies in how different pathologists interpret slides. This conversation explores the reasons for different histopathologists differing consistently in how they interpret liver slides.
One of the primary drivers of reassessing the role of semi-quantitative histopathology in assessing developmental drugs was the paper "Complexity of ballooned hepatocyte feature recognition: Defining a training atlas for artificial intelligence-based imaging in NAFLD," e-published in January 2022 in the Journal of Hepatology. This paper demonstrated strong systematic flaws in the reading of ballooned hepatocytes, which is one of the pivotal factors in assessing drug efficacy. This paper showed that low levels of inter-reader consistency led to an array of interpretive challenges. In this episode, last co-author Quentin Anstee led the Surfers, including co-author Stephen Harrison, through a review of the paper and a discussion of how to resolve this issue.
This conversation starts with Stephen Harrison noting that the single largest problem facing drugs in development is the inconsistency in efficacy reads (and particularly placebo response rates) at the back end of clinical trials. From here, the group explores how histopathology training leads to variability in the interpretation of slides and inconsistent assessments of drug efficacy.
Our week of "Greatest Hits" episodes from the vault continues with this conversation from the episode reviewing the NASH Patient-Focused Drug Development meeting sponsored by the Global Liver Institute and held at the FDA on November 4, 2021. This conversation focuses on the perspectives that patient advocates brought to this session.
Late 2021 and early 2022 traced a series of events that sensitized FDA to the need to look "beyond the biopsy" (or at least semi-quantitative reads) to an approach that would more accurately reflect the benefits of NASH drugs in development and the extreme need patients and their advocates felt for new medications. One critical event on this path was the patient-focused drug development (PFDD) meeting the Global Liver Institute organized and held at FDA on November 4, 2021. At this meeting, FDA reportedly acknowledged that if they had understood patients' perspectives better a couple of years earlier, the path of NASH drug development might have been different.
As I wrote at the time: In this conversation, Global Liver Institute Founder, President and CEO Donna Cryer describes the history of the basic Patient-Focussed Drug Development concept and this particular NASH event. Patient and patient advocate Terri Milton discusses the message she hoped regulators would take away from this session and why she believes the group may have succeeded. Finally, the group discusses why regulators and advocates vary so greatly in terms of how they view the efficacy:safety tradeoff for first-in-class drugs.
Our week of "Greatest Hits" episodes from the vault continues with this conversation from the episode announcing the launch of the NAIL-NIT consortium. Stephen Harrison and Mazen Noureddin discuss the thinking behind their new consortium and its targets. In this conversation, they discuss challenges with the NAS score.
The early part of 2022 had several episodes discussing the increasing need to move beyond biopsy (yes, semi-quantitative, but even AI-assisted at some levels) to a future shaped by NITs. One pivotal issue that emerged regarded ballooned hepatocyte evaluation and its impact on NAS scores.
As I wrote: The first section focuses mostly on what we can and cannot learn from a NAS score, and implications of its shortcomings on the drug development process. After this, Stephen Harrison notes the complex role the liver plays in energy transfer throughout the entire metabolic process. This suggests that the effects of Fatty Liver disease vary among individual patients and, as a result, drug development and patient diagnosis and treatment should provide sufficient insight to optimize each patient's therapy. As the conversation closes, Mazen Noureddin is responding to a question from Louise Campbell about what we will learn about optimal testing strategy. Mazen suggests there is unlikely to be a single "winning" test but, instead, a combination of NITs probably will be necessary to answer all the questions necessary to optimize therapy.
Our week of "Greatest Hits" episodes from the vault continues with our second most popular conversation ever, which came from the wrap-up episode for AASLD2021. In this episode, Manal Abdelmalek, Jörn Schattenberg and Ian Rowe joined Stephen Harrison, Louise Campbell and Roger Green to recap NAFLD and NASH-related insights from AASLD2021 TLMdX and specifically to focus on how NITs will help, in the words of Stephen Harrison, "put a big, fat dent in Fatty Liver disease."
As I wrote at the time: The conversation starts with the group congratulating Manal Abdelmalek on her wrap-up NAFLD talk at the 2021 TLMdX. From there, the group focuses on the shortcomings of using biopsy as the clinical trial gold standard and how strategic clinical trial design and interpretation of existing NIT data can build a bridge from biopsy through MRE/biopsy correlations to a total NIT future.
Our week of "Greatest Hits" episodes from the vault continues with our most popular conversation ever, as Stephen Harrison and Jörn Schattenberg synopsize the Basic Science segment of the recent Paris NASH meeting. This segment, which focuses largely on a state-of-the-art look at fibrosis, is by far our most downloaded conversation every, with more volume than the next four posts combined!
As I wrote at the time: Paris NASH is a meeting for basic science and interdisciplinary thinking. Since Stephen Harrison was drafted into co-chairing the session titled "Deep Dive into Fibrosis," he led this conversation. The session included three presentations with a powerful collective message about stellate cells: that different stellate cell subtypes perform in unique ways in terms of how they function, the process(es) through which they become modified and what this represents in terms of performance. This description does not do Stephen and Jörn's comments justice. It's a short session, so listen for yourself...
Our week of "Greatest Hits" episodes from the vault continues with Scott Friedman's fascinating presentation on precision medicine in the context of senescent stellate cells and fibrosis, first posted in October 2021. Scott combines erudition and unparalleled knowledge of the subjects he is discussing with a storyteller's ability to paint clear pictures and make complex issues both simple and lively.
Scott, known to some as the "Father of Fibrosis," starts this discussion talking about his own history in fibrosis research and then the history of the stellate cell and its role in where precision medicine is heading. The rest of the episode touches on issues ranging from the importance of omics in learning about the disease and the future of precision medicine to target disease to today, specifically, the downside of being, as Scott puts it, "yoked to biopsy." In the aftermath, listeners (including other leading KOLs) described this episode as a "coup," a "treasure" and "something you can find only at Surfing the NASH Tsunami." If you missed this episode the first time around, download it now and make it your weekend (or vacation week) listen.
Our week of "Greatest Hits" episodes from the vault starts with Jörn's first featured episode, which we posted in November 2020. The episode focused on a recent article he co-authored looking at why so many NASH drug trials fail. One key issue: proper utilization of Phase 2 trials. At the time, we wrote:
Jörn Schattenberg joins Stephen, Donna, Louise and Roger to discuss his recent article "The Nonalcoholic Steatohepatitis (NASH) drug development graveyard: established hurdles and planning for future successes." The discussion starts with lessons from failed trials, focusing on the importance of utilizing Phase 2 trials to test hypotheses and establish appropriate targets. From there, Surfers went on to discuss commercial and patient-focused definitions of what makes a clinical trial successful.
Surfing the NASH Tsunami posted on Buzzsprout for the first time on July 23, 2020. Over the past two years, NASH Tsunami has posted 132 episodes and close to 400 posts when we include both episodes and conversations. This week, Jörn Schattenberg and Roger Green review some of the podcast's high points and set the stage for a week of resharing "Greatest Hits" episodes and conversations from the Vault of old postings.
The conversation starts with Jörn and Roger reminiscing about Jörn's first couple of appearances on the podcast, first helping to review the digital ILC 2020 and then coming on a couple of months later to discuss a paper Jörn had recently published looking at why NASH drug trials fail. Jörn and Roger discuss come of the lessons from the paper and how those have translated into changes in drug development and clinical trial strategies.
One interesting side note: Roger asks Jörn about feedback from the original paper. He comments that the authors rarely get feedback, especially those who are not the correspondent author (which Jörn was not for this paper). He commented that he receives more feedback from the discussions on NASH Tsunami, either on the podcast or in subsequent conversations with friends and colleagues who have heard the episode.
Roger goes on to note that while the "Why Trials Fail" paper touched on challenges around biomarkers and conditional endpoints, we were only at the beginning of learning how many flaws existed in the system of semi-quantitative reads. This serves as a bridge to the specific conversations NASH Tsunami will repost from the Vault during this anniversary week. They address topics ranging from stellate cell activation to the role of NITs to the importance of patient advocacy. As they move from post to post, Jörn and Roger provide context on where each one fits in the history of the podcast and what they learned or experienced as a result.
Of course, a podcast without Stephen or Louise can provide only so much of the podcast's history and key moments, but for listeners, this episode will give you an opportunity to reflect on your own intellectual journey with NAFLD and NASH and to ask yourself which of the older episodes and conversations you might want to revisit. As we noted earlier, we will post two episodes and six conversations we like to revisit in the week ahead.
his week, Surfing the NASH Tsunami returns to a subject we have explored from time to time over the past two years: helping patients with cirrhosis. While the immediate stimulus for doing so was the semaglutide late-breaker at #ILC2022, our more general interest is that many patients with cirrhosis will start to decompensate and decline in a fairly short period of time. This conversation brings together key threads from earlier in the episode, focusing significantly on providing better cirrhosis patient support as a key element in improving NASH cirrhosis therapies.
As this final conversation starts, Jörn Schattenberg and Lars Johansson are discussing two points: (i) the idea that even when a patient is diagnosed, this might not make it into that patient's medical record or become a focus of therapy, and (ii) the idea that the 30,000-patient study Lars has mentioned is focusing on deriving outcomes without biopsying patients. Louise Campbell joins in to endorse both these ideas, focusing more on capturing patients' NAFLD, NASH or NASH cirrhosis in the medical record and making it actionable. In particular, she notes that the investment necessary to improve communication will be far lower than what will be necessary to create or dramatically enhance drugs and diagnostic technologies.
This leads to Roger Green's closing question about a likely area for short-term improvement in a treatment area the panelist touches every day. Panelists' answers are diverse and thought-provoking.
This week, Surfing the NASH Tsunami returns to a subject we have explored from time to time over the past two years: helping patients with cirrhosis. While the immediate stimulus for doing so was the semaglutide late-breaker at #ILC2022, our more general interest is that many patients with cirrhosis will start to decompensate and decline in a fairly short period of time. This conversation focuses on what Roger Green describes as a "pincer movement" in technological development: high-end technology to empower better diagnosis, staging and treatment and low-end technology to capture more patients, capture them earlier in disease and keep them engaged in the process.
The conversation starts with Roger posing a question of whether the major need in improving cirrhosis diagnosis and treatment is a human systems or a medical technology issue. After some conversation, the answer turns out to be "both."
Louise Campbell responds first. She focuses on human systems needs: send the right letter, engage the patient and provide the proper and necessary information to educate the patient and keep them involved. She goes on to note that (i) these needs appear to be global in scope although the challenge takes different forms in different countries; and (ii) for patients with progressive disease, "not feeling worse" is an outcome they will pursue aggressively.
This observation, coming after earlier discussions about medical treatment issues, leads Roger to make his "pincer movement" comment. Jörn Schattenberg agrees that there is a "disparity" between investment in high-end medical technologies and physician and hospital office systems that rely on older technology and inadequate systems. He states that he considers it important to invest in health structure improvements as well as advancing technologies.
Roger asks Lars what role high-end technologies will play in advancing patient care. Lars suggests that technology's major role will be in driving better decisions about which drugs to develop and how. He goes on to state that advances in clinical practice need to be simple, affordable and practical. The example Lars gives is an effort years ago to persuade Swedish patients with dyslipidemia and cardiovascular disease to focus on Apo B instead of LDL. The task became impossible because, in spite of more compelling data on Apo B, the concept of LDL-lowering as the therapeutic target was so well embedded that it proved impossible to dispel, or even modify meaningfully.
As this conversation winds down, Roger asks Lars to describe work he is doing that will benefit patients. Lars talks about exploring the effects of cirrhosis on other organ systems, specifically the heart and kidney. Jörn follows up with a question about deploying standard imaging (his example is back pain) to identify previously undiagnosed liver issues. Lars responds by discussing an AI-aided study he is working on with 30,000 patients looking at multi-organ imaging issues using CT. He suggests that in the future, simply having a section of liver in the CT will provide this kind of guidance.
This week, Surfing the NASH Tsunami returns to a subject we have explored from time to time over the past two years: helping patients with cirrhosis. While the immediate stimulus for doing so was the semaglutide late-breaker at #ILC2022, our more general interest is that many patients with cirrhosis will start to decompensate and decline in a fairly short period of time. This conversation focuses on a specific question: where is the next breakthrough in cirrhosis patient management likely to come?
This conversation starts with Roger reflecting on a comment Lars had made during a previous appearance on the podcast, that we should spend more time focusing on what should be happening in the liver instead of what shouldn't. Lars notes one reason for this: when we look at other organ systems (heart or kidney, for example), we focus on how the organ functions. With the liver, we read static biopsies that do not measure actual function. He goes on to note that researchers are developing functional tests, many of which require labeled compounds and then record how they move through the body.
At this point, Roger shifts the discussion by asking the panel where members anticipate the next major breakthrough in improving cirrhosis diagnosis and treatment. Louise responds first by noting the need to pick up patients earlier in the course of the disease as they move through the healthcare system. She envisions that this may come by adding. FIB-4 to every patient coming through the system or perhaps to something like the iLFT that John Dillon described at the Barcelona meeting. Even there, she notes, the system picks up only 50% of diseased patients. Jörn describes the need to improve diagnostic performance, both in terms of better tests and better ability to deliver both testing and results to patients. Lars questions whether the answer lies in providing imaging tests for every patient. Instead, he suggests, we need to link imaging results more closely to liquid biomarkers and then drive universal, early use of these less expensive liquid tests. As the conversation ends, Louise agrees with this point but notes again that we are assuming a level of patient communication and provider follow-through that does not exist today.
This week, Surfing the NASH Tsunami returns to a subject we have explored from time to time over the past two years: helping patients with cirrhosis. While the immediate stimulus for doing so was the semaglutide late-breaker at #ILC2022, our more general interest is that many patients with cirrhosis will start to decompensate and decline in a fairly short period of time. This conversation begins to explore the ability of currently available medications to cause fibrosis regression in patients with cirrhosis.
This conversation starts with Lars posing a question to Jörn: does he believe that a "drug like sema[glutide]" can inhibit the progression of fibrosis, even though the #ILC2022 late-breaker showed no significant level of fibrosis regression over a 48-week period. Jörn replies that the study demonstrated that semaglutide was safe and demonstrated some effects (on transaminase levels, for example), but nothing on fibrosis. He then turns the question back to Lars to ask what metabolic or systemic effects we might measure as a precursor to fibrosis regression or even lack of progression. Lars points to subclinical signs of possible portal hypertension as one place to look. In this context, he notes that increases in spleen volume as modest as 20-30% can be linked to increasing fibrosis levels and possibly changes in portal pressure. As a result, he suggests, looking at changes in portal pressure might be a fruitful area for exploring the ability of a medication to regress fibrosis or even just to stop progression. Lars notes this could be reduced inflammation that has not yet translated into fibrosis regression. As he points out, bariatric studies show it can take years to regress fibrosis.
Roger asks the group which parameters they consider signs of fibrotic stabilization or regression. Jörn notes Lars's earlier comment about HVPG and asks which measures correlate with it. He mentions varices and ascites as signs to watch as the disease progresses. Finally, he asks about how well patients with compensated cirrhosis perform on other performance metrics.
Lars answers that performance is "not that bad in terms of other effects" and goes on to describe some of the other measures he and others are exploring. As the conversation ends, Lars points out that reducing activation of stellate cells would be a good thing in itself, regardless of whether or how long it takes to lead to fibrosis regression.
This week, Surfing the NASH Tsunami returns to a subject we have explored from time to time over the past two years: helping patients with cirrhosis. While the immediate stimulus for doing so was the semaglutide late-breaker at #ILC2022, our more general interest is that many patients with cirrhosis will start to decompensate and decline in a fairly short period of time. This first conversation begins to look at the importance of identifying cirrhotic patients as early in the disease process as possible and the diagnostic tests that are most helpful in coming to a diagnosis. (Ideally, patients will be diagnosed long before they become cirrhotic, but many patients are never diagnosed with or treated for NASH before progressing to cirrhosis.)
Roger Green starts this conversation by discussing NASH Tsunami's history of cirrhosis episodes and the issues we have focused on. At that point, he turns to Jörn Schattenberg to discuss the importance of diagnosis and the tools available to do so.
Surfing the NASH Tsunami has explored issues of NASH cirrhosis since our earliest episodes in 2020. This episode integrates panelists with three different perspectives to consider the most important challenges in treating patients with NASH cirrhosis today. Jörn Schattenberg was an author of the #ILC2022 late-breaker presentation discussing semaglutide in NASH cirrhosis. Antaros Medical co-founder and Chief Scientific Officer Lars Johansson has discussed and published on different ways to evaluate the impact of medications on cirrhosis. Louise Campbell's career in nursing and subsequent work at Tawazun Health has focused on providing patients with the information and support they need to improve their own conditions.
Roger Green starts the dialog by recounting the cirrhosis discussions over the life of the podcast, starting with discussions about using older medicines (statins, metformin) that might benefit patients, a significant number of which might decline relatively quickly. Jörn Schattenberg picks up this line of discussion, then goes on the describe the semaglutide late-breaker at ILC2022. Jörn notes that while the study failed to achieve fibrosis regression in 48 weeks, it improved a range of metabolic markers while demonstrating a strong safety profile in this population. Jörn goes on to note the importance of early (okay, earlier) diagnosis in these patients and notes that ELF is indicated in the US and EU to confirm a diagnosis of cirrhosis.
Lars Johansson joins the conversation to ask Jörn whether he believes 48 weeks is enough time to expect fibrotic regression in cirrhotic patients. After Jörn concurs, Lars comments that effects seen with sema in this population (20-30% reduction in spleen volume and early signs of portal pressure changes) suggest we are "doing something good" even if the drug did not regress fibrosis within the study period.
Lars goes on to discuss triggers that tell him how well (or poorly) the liver and overall metabolic system are working in a target patient. When evaluating other diseases (heart, kidney), he points out, we look directly at organ function. With liver, he notes, we look at biopsies.
At this point, Roger asks the group where the next breakthrough in cirrhosis therapy is likely to occur. Louise points to the need to improve patient communications, given how many patients do not learn they have ANY liver disease until their initial cirrhosis diagnoses. Jorn states that a key to improving communications and educating front-line physicians is to create simple, automated measures that will allow the patient's risk status to appear on an electronic medical record. Lars foresees a major breakthrough when we can study imaging results along with circulating biomarkers in order to identify a single biomarker (or a small group of them) that can predict advanced disease.
Louise returns to the point that without improved communications, we will fail to keep patients engaged in their own therapy, which will have severe consequences. This leads Roger to describe the next stage as a "pincer movement," with high-tech diagnostics and new drugs on one end and better human systems engineering and electronic communication on the other.
Next, Roger asks Lars where he believes what he is learning will translate into improved diagnostics. Lars and Jörn agree that the best strategy is a first stage of inexpensive screening to rule out patients without disease, and then probably a CT-based evaluation to appreciate the status of the liver and impact on related organ systems.
As the conversation wraps up, Roger asks where each panelist sees the greatest potential for growth in the next 1-2 year. Louise and Jörn focus on improved patient communication and simple screening, while Lars talks with excitement about starting to garner large amounts of data from some of the large, long-term outcome studi
On July 7, Intercept Pharmaceuticals released new results from the continuation of the REGENERATE trial and announced their intent to file a new NDA for obeticholic acid (OCA) in NASH fibrosis. In this conversation, Stephen Harrison leads Jörn Schattenberg, Louise Campbell and Roger Green in considering whether the evidence in the new release will be sufficient to get the drug approved.
Stephen starts by noting that we have not heard anything about the results of the REVERSE trial, which evaluated obeticholic acid (OCA) in patients with compensated cirrhosis. As he notes, even if OCA is not approved for cirrhosis, many hepatologists will consider giving this drug to cirrhotic patients, particularly compensated cirrhotics who face a significant worsening of their condition in a fairly short period of time.
Jörn comments on this briefly to agree that the cirrhosis data will create a complete data set, then returns to the pruritus issue. Mostly, his point about cirrhosis is that given the high placebo rate suggests there is "something about how the question is asked." He finishes this comment by discussing the importance of getting a first drug approved and stating his anticipation of what happens when FDA reviews these data.
Roger goes on to note that he has a unique experience in this group: he has discontinued a drug therapy based on pruritus (in his case, a cancer drug). Having lived through that experience, he expresses skepticism that pruritus that resolves on discontinuation will be a reason for the drug to be rejected. Stephen concurs, and Roger goes on to state that the perceived cardiovascular risk in 2020 made sense as a reason not to approve, but not pruritus. Stephen and Louise concur that we will not know the entire story until we know the lengths to which providers went to keep patients in this study, but both are hopeful (and pretty much expect) that while there may be boundaries on patient types and guidance on treatment, the case for approval appears likely to succeed.
During the second half of this conversation, panelists share their common hope that this data will be sufficient to get OCA approved and discuss what this could mean for the entire Fatty Liver stakeholder community.
On July 7, Intercept Pharmaceuticals released new results from the continuation of the REGENERATE trial and announced their intent to file a new NDA for obeticholic acid (OCA) in NASH fibrosis. In this conversation, Stephen Harrison leads Jörn Schattenberg, Louise Campbell and Roger Green in considering less obvious questions surrounding efficacy and safety.
Stephen starts this conversation by asking the group how important it is for a drug (in this case, obeticholic acid) to show a combined endpoint of fibrosis improvement and NASH resolution. He notes this is a tougher standard to hit but notes that it might be quite important.
Jörn describes this comment as a "good point" that probably was not addressed due to the low level of NASH resolution when viewed as a primary endpoint. Louise says she would need to know more about the diets patients were on while in the trial given the effect diet can have on liver fat. She then goes on to say that one question she would like to have answered is how many patients needed counseling on their pruritus to stay in the study and what exact steps did researchers take to keep these patients in. She points out that knowing the steps necessary to maintain patient adherence is vitally important to caregivers but rarely reported for trials, if ever.
Roger makes two points. His first basically supports Jörn's comment that the low level of NASH resolution as a primary endpoint virtually guarantees that the number of patients achieving the dual endpoint will be minimal at best. His second harkens back to Stephen's earlier point about including a larger post-18 month patient pool in the efficacy analysis. To Roger, it appears that Intercept made the sound commercial decision to reveal only the data necessary to generate the analyses necessary for approval. It felt to him as if Intercept assessed the least risky way to refute each point in the CRL, and then did only the analyses necessary to refute points successfully. In essence, Roger describes the analysis as a way to de-risk the drug and believes they appear to have done so effectively.
At this point, Stephen shifts direction. He gives Intercept "accolades...they didn't give up. They persevered. They continued to drive forward and they added three different adjudication committees." And while he believes there is more analysis to be done, he describes the contents of the press release as "a very, very positive implication for the field" and "give[s] it two thumbs up."
After Roger concurs, Stephen goes back to Louise's questions about pruritus and notes that the methodology for evaluating pruritus might have produced overstated results. In essence, the investigator asked patients whether they were experiencing pruritus at every visit, an approach Stephen and Jörn believe was likely to produce an overstatement on itching. Stephen continues this line of thinking to note that investigators were forced to discontinue therapy under certain pruritus reports. As the conversation ends, he notes that he is far more interested in hepatic effects.
On July 7, Intercept Pharmaceuticals released new results from the continuation of the REGENERATE trial and announced their intent to file a new NDA for obeticholic acid (OCA) in NASH fibrosis. In this conversation, Stephen Harrison leads Jörn Schattenberg, Louise Campbell and Roger Green in examining how the larger sample and longer time patients were on therapy changed the safety and tolerability profile from the initial analysis.
After reviewing the four key points from Intercept's press release, Stephen Harrison kicks off this conversation by discussing the safety evaluation, which included a far larger population with significantly longer exposure to study drug. After describing the enriched population, he quotes from the press release, "Emergent adverse events treatment, emergent serious adverse events, and deaths were generally balanced across the OTC and placebo treatment groups." He goes on to cite the considerable differences in pruritus across groups (22% in placebo, 33% in 10mg and 55% in 25mg), share the comment that most discontinuation stemmed from pruritus, note that gall bladder-related events occurred in less than 3% of patients and, finally, that OCA 25mg had a higher rate of biliary events. He then asked the rest of the group for comments.
Jörn commented first, noting that this was mostly "recapitulated" data, but with a much broader set of subjects. Because risk:benefit ratio was perceived as the pivotal issue around the time of the original Complete Response Letter (CRL), he describes the data as improved "by a lot."
Louise describes as "reassuring" the idea that the NASH dose could be so much higher than the approved PBC dose (25mg vs. 5 or 10mg) but not demonstrate additional safety concerns. She goes on to declare that practices planning to use OCA should be "planning pathways into delivery" in anticipation that the high level of pruritus will lead to a significant set of discontinuation with a careful approach to patient orientation and management.
Roger shared his recollection that increases in LDL levels and the implicit associated cardiovascular risk were major issues in the negative risk:benefit assessment, but that this analysis appears to report that levels returned to normal within the first year of treatment. This might increase chances for approval.
At this point, Stephen reads the press release carefully to identify potential safety hazards that are not addressed directly in the document, although, as he notes, one can fit only so much into a press release. As the conversation ends, Stephen asks Jörn if he has "ongoing lingering questions". Jörn notes that he wondered how the reads were done and that he also looked for LDL data. He makes a few other points, but suspects that they may have been covered in the 2019 paper.
On July 7, Intercept Pharmaceuticals released new results from the continuation of the REGENERATE trial and announced their intent to file a new NDA for obeticholic acid (OCA) in NASH fibrosis. In this conversation, Stephen Harrison leads Jörn Schattenberg, Louise Campbell and Roger Green in examining the new efficacy analysis and exploring what it means for obeticholic acid, both in terms of the drug's performance and its revised prospects for FDA approval.
After reviewing the four key points from Intercept's press release, Stephen Harrison kicks off this conversation by looking at a broader efficacy picture than mere regression of fibrosis, to ask what percentage of patients experienced no further progression of fibrosis compared to the placebo group. Stephen notes that the clinical value of simply halting fibrosis progression in an F3 patient is tremendously important because it allows an asymptomatic patient to continue life at its current level of quality. He adds, "we can manage co-morbidities" separately. He goes on to wonder why Intercept did not expand the analysis to include the large number of patients who made it past the 18-month biopsy time point but were not part of the original 2019 efficacy cohort.
At this point, Stephen takes a step back from the actual data to describe how the consensus approach worked on histological reads and to praise the approach for providing clear, simple answers. Jörn Schattenberg picks up the conversation by agreeing with Stephen's assessment of the consensus approach, which he describes as emulating how colleagues assess challenging cases or histopathology reports in actual practice.
Roger joins the conversation to wonder why the consensus reading process would have the effect of reducing the percentage of patients who improve in the placebo group on one reading but not elsewhere. More important to him, he goes on to agree with the idea that if this agent regresses fibrosis in some cases but halts progression in most or all, it might become a valuable part of a combination therapy that includes other agents with a stronger effect against steatosis than fibrosis.
Thinking from a patient perspective, Louise notes that consensus reads should give the patient greater confidence in the results. In terms of confidence and border reads, Stephen points out that some of the presentations at the recent ILC2022 meeting that drugs that have an impact on NASH might also affect liver volume. (He notes that the open-label cirrhotic cohort of the resmetirom trial MAESTRO-NAFLD 1 also showed spleen volume reduction and an inverse effect on platelet count.) Setting aside the cirrhosis results, he notes that if we start to measure liver volume when conducting biopsies, we can correct estimates of the impact of fibrosis to account for changes in "what we see" based on changes in liver volume. As the conversation ends, he notes that this might be a fruitful topic for future research that can translate into patient treatment.
On July 7, Intercept Pharmaceuticals released new results from the continuation of the REGENERATE trial and announced their intent to file a new NDA for obeticholic acid (OCA) in NASH fibrosis. In this conversation, Stephen Harrison leads Jörn Schattenberg, Louise Campbell and Roger Green in examining the new efficacy analysis and exploring what it means for obeticholic acid, both in terms of the drug's performance and its revised prospects for FDA approval.
After Stephen lists the four major bullet points from Intercept's press release, this conversation focuses on the first point: "The 25mg dose of obeticholic acid met the agreed primary endpoint of improvement in liver fibrosis without worsening of NASH at 18 months." The data behind this bullet point stem from a new interim analysis of the original 931 cases. In the re-analysis, the treatment effect remained constant but the placebo effect dropped slightly. The different results from a different method of analyzing histopathology, one that relied on consensus panel reads instead of an individual histopathologist's interpretation (as was done in the original analysis). Stephen goes on to note that there is a similar small change in the NASH resolution percentages, but, like the original analysis, these do not reach statistical significance. He notes that this submission relied on hitting one of the primary endpoints, not both of them. He then asks the group two questions: "Does this change our perception of OCA in NASH?" and "Does this change our perception of this drug as a driver of the field in drug development for NASH?"
Roger answers first. Taking a narrow focus on the question, he answers that we still see OCA as an effective anti-fibrotic at the same level we did three years ago. If there is a change, it is that if obeticholic acid had a three-year lead on the market, it would have focused a significant amount of research on FXR agonists -- both in terms of developing more FXRs and in considering them the backbone in NASH pharmacotherapy. In 2022, with another very different agent appearing to be fairly close to market, he felt these results would not dramatically change the other directions in which research is heading.
Jörn Schattenberg goes back to the original 2019 paper, which he describes as "groundbreaking" and, quoting Zobair Younossi, "a watershed moment." He notes that the reading method seems more consistent with what FDA wants and says that while others may comment on the small effect size (11%), his view is that this is a positive achievement as the first paper to demonstrate significant effect against fibrosis.
Louise Campbell echoes her colleagues' comments about the successful efficacy results but notes that patients who could have benefitted from OCA's approval two years ago have gone two more years without the benefit of medication.
Stephen concludes the conversation by agreeing with Jörn that this is a watershed moment. He notes how many observers have said that proving efficacy was essentially impossible due to the complexity of the disease and regulators "moving the goalposts." This study, he says, proves that it can be done.
On July 7, Intercept Pharmaceuticals released new results from the continuation of the REGENERATE trial and announced their intent to file a new NDA for obeticholic acid (OCA) in NASH fibrosis. In this episode, Stephen Harrison leads the Surfers through a discussion of the new REGENERATE results and the Surfers discuss what they find compelling in the new data, discuss the possibility of approval, and ask (and answer) what an approval might mean for the Fatty Liver community.
The basic structure of this episode is: Stephen Harrison walks the group through issues, opportunities and considerations raised in the July 7 press release and the rest of the panel responds with comments and questions as appropriate. He starts by noting that in a recent episode, the Surfers identified the release of updated REGENERATE data and subsequent OCA approval in NASH fibrosis as a potentially transformational event in the Fatty Liver community and proceeds to read the four bullet points that Intercept Pharmaceuticals highlighted:
- The 25mg dose of OCA met the agreed primary endpoint of improvement in liver fibrosis without worsening of NASH at 18 months.
- The 25mg dose of OCA doubled the fibrosis response rate vs. placebo.
- This data set includes larger and more robust safety database of 2477 patients with nearly 1000 on study drug for four years.
- Intercept will refile an NDA in liver fibrosis due to NASH, starting with a pre-submission meeting with the FDA later this month.
From there, Stephen dives into the data, starting with the efficacy results. He notes that the results for reduction of fibrosis without worsening of NASH are comparable to the initial REGENERATE results statistically: highly significant improvement in the 25mg dose vs. placebo, but not in the 10 mg dose. He also notes a small but statistically insignificant numerical difference in NASH resolution without worsening of fibrosis. The 25mg score is roughly the same as in the earlier trial, but the placebo score dropped, possibly due to a change in the methodology for reading histology slides . In the previous analysis, two histopathologists each read half the slides independently. This time, two teams of three histopathologists read slides in a design that forced consensus on each slide included in the final data.
In discussing efficacy data, Jörn describes this study as "groundbreaking" and Louise notes the impact of a two-years-later approval in terms of patients who did not receive drug benefit over that time. In agreeing with Jörn, Stephen notes that this study proves that we can get a fibrosis drug "over the finish line" by meeting FDA efficacy criteria.
The group moves on to discuss safety criteria. Stephen notes that pruritus is still the most common side effect and reason for discontinuation, while Roger comments that LDL and cardiovascular issues, which were implicated as the major risk issue in the earlier data, appear to resolve over time and not present as much risk this time. Jörn and Louise both praise the increased robustness of safety data based on sample size and duration of therapy, after which Stephen notes the questions that the press release does not answer (but, presumably, the full data release will).
The rest of the discussion focuses on some decisions Intercept made about how to present data and the overall implications of this trial. Stephen and Roger praise Intercept for their continued commitment to OCA in the face of FDA's 2019 Complete Response Letter and the group agrees that this data is more likely to gain approval. When Roger asks for a prediction of what the world might look like 1-2 years from now, the group considers that we might have two approved agents (with resmetirom) as early as the end of 2023.
Last month, roughly 5,000 liver community stakeholders gathered in London for the 2022 International Liver Congress (#ILC2022.) On Thursday afternoon, Scott Friedman chaired an abstract session discussing advances in the basic liver science of researching and understanding mechanisms surrounding fibrosis and stellate cells. Later, he described it as "one of the most exciting groups of presentations I've seen in many years." After this extremely rich and engaging discussion of advances in research processes and the findings the group discussed, Roger Green asked the group with the impact of advances like these will be over the next "year, three years, five years."
The answers vary significantly from one panelist to another, in each case reflecting where the panel members touch the healthcare system and product industries. Scott discusses the ability of research to create completely new classes of therapies with previously unimaginable impact on disease, citing CAR-T as one example that is already in use. Louise Campbell makes a vastly different but very important point: it will work better for everyone if we can create more tissue samples, and the ability to generate these kinds of advances will make it easier for providers to ask patients to provide tissue samples and will increase the number of patients who say, "Yes." Scott and Neil both note how good and important a point this is, with Neil stating that the growth in data we can produce from tissue is "exponential," and that this data is key to creating better disease understanding, diagnostics and drugs. Rachel discusses two key areas where the cost of research is decreasing: the availability of open-source data sets and the cost of actual sequencing. Jörn suggests that having a richer understanding of disease will reduce the number of drug failures, partly because we will know how to capitalize on what we are learning and partly because we may not rush into major drug trials where we lack elements of basic understanding. Roger closes with two summary points: (i) that the technologies the group discussed will be applicable not only for NASH but an array of other liver diseases, and (ii) that over the past three years, the field has created a vastly larger number of data points which is starting to look less like scattered points and more like connected dots making an actual picture.
With these final notes of optimism and energy, the group closed the discussion.
Last month, roughly 5,000 liver community stakeholders gathered in London for the 2022 International Liver Congress (#ILC2022.) On Thursday afternoon, Scott Friedman chaired an abstract session discussing advances in the basic science of researching and understanding mechanisms surrounding fibrosis and stellate cells. Later, he described it as "one of the most exciting groups of presentations I've seen in many years." The conversation starts with Roger Green asking the panel how to pay this research off in terms of commercial benefit. Most of the conversation consists of their answers.
Scott Friedman answers Roger's question first. He notes that these advanced techniques will allow us to focus on not only the right type of cell but the right subtype(s). Hitting the right target dead-on will improve the efficacy of drugs and the accuracy of diagnostics. Also important (perhaps more so): we can avoid what Scott calls "off-target effects", which commercial executives might think of as safety, tolerability and side effect issues.
Consistent with other themes NASH Tsunami visits regularly, Jörn notes that the future of therapy is likely to be individualized, multi-element, and probably multi-phase. The more this basic research can teach us about the disease process stages and how they vary by patient, the better job drug developers can do in developing medicines that resolve specific patients' needs.
Scott notes that if we can hypothesize which patients will respond best to a specific intervention, we can streamline clinical trials, possibly reduce sample sizes, separate respondents from non-responders better and/or shorten trial durations. All these possible outcomes stem from the increasingly demonstrable reality that NAFLD or NASH is actually a set of related diseases rather than a single, uniform disease process.
As the session begins to wind down, Roger invites Scott to discuss any other topics that emerged from the abstract session. Scott mentions the last paper in the session, where researchers from Heidelberg explored a specific receptor whose acronym is RAGE (Receptor for Advanced Glycation End-products). RAGE drives what Scott terms "a very important response," seen both in NASH and cholestatic disease, in which bile ducts proliferate. This is called a ductular reaction. As Scott notes, both the cause of this reaction and its relationship to fibrosis have been "a bit hazy." Now, this group has identified some players that might be involved in this process...and identified them in such a way that therapeutics are being developed against RAGE. This will benefit NASH and, even more clearly, cholestatic diseases.
As the last question before wrapping up, Roger asks the rest of the panel if they have comments about the meeting aside from this session. Neil points to the optimism and energy caused not only by the new methods but also by the sharing of knowledge AND larger data sets, all of which can lead to molecular pathology-based approaches that will help us define the multiple diseases in the NAFLD galaxy better. Jörn goes almost to the other extreme, commenting on presentations demonstrating the value of FIB-4 as a first-line screening tool and others challenging FIB-4 the same way. To Jörn, this identifies the need for a better first-line screening test, which the kinds of research covered in this session might produce. Roger closes the conversation by noting that the two outstanding benefits of FIB-4 are its low cost and wide availability, which suggests the next steps we are more likely to see is a staged approach to diagnosis and screening.
Last month, roughly 5,000 liver community stakeholders gathered in London for the 2022 International Liver Congress (#ILC2022.) On Thursday afternoon, Scott Friedman chaired an abstract session discussing advances in the basic science of researching and understanding mechanisms surrounding fibrosis and stellate cells. Later, he described it as "one of the most exciting groups of presentations I've seen in many years." This conversation centers on papers with similar methods and processes for researching stellate cells.
Scott begins this conversation by describing this process, which is based on another Nobel Prize-winning methodology. In this technique, the researchers start by forcing an adult mature skin cell (or any cell, for that matter) o express a cluster of very well-defined genes and transcription factors, which the researcher then turns into a generalized, Induced Pluripotent Stem (IPS) cell. Researchers have found ways to convert these IPS cells into stellate cells. The developer of this technique posited that it will enable us to explore the proteome.
To Scott, this process of converting a generalized cell to a stellate cell we can analyze via proteomics to find new targets is more important and noteworthy than the result of this specific study (researchers identified a novel nuclear receptor called RORalpha). To quote Scott, "they're much closer to the action when they find a protein rather than just the mRNA that encodes it." He goes on to discuss a second study from Insitro (a company with which he consults) about their work seeking to optimize the IPS-derived stellate cells to find the one that most closely resembles cells in vivo.
When Scott finishes, Neil notes that single-cell proteomics is not "coming, but it's not there yet." Neil anticipates we will have this pivotal tool available in a 1-2 year time horizon. Next, Jörn anticipates and asks about the next stage in the process: identifying a protein related to this process we can find in peripheral blood given that, as Neil noted, tissue sampling in the clinical setting will not be possible. Scott discusses a recent paper that seems to provide a solution to this issue in breast cancer. While he notes that the work has to be validated first, it clearly suggests researchers are close to finding proteins we can identify in blood in at least one cancer-related case.
From there, Scott turns to Rachel for feedback, since this is the area in which her business is building its research. Her answer has several elements to it, but the main point is that proteomic development lags behind some of the other techniques but is making rapid advances as the costs of some key analytical processes come down. She then goes on to provide a description of epigenetics, the area in which she works most intensively.
Last month, roughly 5,000 liver community stakeholders gathered in London for the 2022 International Liver Congress (#ILC2022.) On Thursday afternoon, Scott Friedman chaired an abstract session discussing advances in the basic science of researching and understanding mechanisms surrounding fibrosis and stellate cells. Later, he described it as "one of the most exciting groups of presentations I've seen in many years." This presentation centers around two papers that explore stellate cell dynamics related to the progression and regression of fibrosis, both of which rely on methods pioneered by Neil and his colleague Prakesh Ramachandran to take individual cells from tissue (in this case, the liver), use transcriptomic to interrogate the mRNA and infer how cells interact in different processes.
The first presentation, which takes up the bulk of this conversation, centers around scar formation in mouse livers under injurious assault and then scar healing when the assault ceases. Before discussing the study itself, Scott provides a brief but extremely rich background of the research technique that are driving progress in this area, including Neil's work and other advances that have been recognized with Nobel prizes.
When the focus reverts to the actual papers, Neil notes that this presentation is unusual in that most research devotes far more attention to scar formation than to regression whereas this note looks at both processes (In Season 2, Episode 50, Lars Johansson noted similarly that researchers spend far more time researching "what shouldn't be in the liver" than what should be there.) He continues that we can research these issues far more effectively in mice than in people, in part because we do not biopsy people with healthy or healed livers. This leads to another brief discussion of methods, in this case, spatial transcriptomic. Jörn asks a clinician question: if there are, as this paper suggests, 14 different states of activation, how do we know which are druggable?
NOTE: The researcher presenting this paper at ILC2022 noted that the research was funded in part by Novo Nordisk.
As the discussion closes, Scott mentions a different paper that touches on the role of peroxidation an antioxidant process, in fibrosis progression. and regression.
Last month, roughly 5,000 liver community stakeholders gathered in London for the 2022 International Liver Congress (#ILC2022.) On Thursday afternoon, Scott Friedman chaired an abstract session discussing advances in the basic science of researching and understanding mechanisms surrounding fibrosis and stellate cells. Later, he described it as "one of the most exciting groups of presentations I've seen in many years." This presentation centers on the relationship between Circadian rhythms and stellate cells.
It is widely known that we all function under a set of Circadian rhythms tied to day/night changes. Original work in this area focused on physiological changes linked to the central nervous system. In recent years, researchers have learned that other tissues in the body operate on their own Circadian rhythms, presumably tied in some way to the central nervous system. But as Scott exclaims when beginning this discussion, "who would have thought that that included the lowly little hepatic stellate cell, a fibrogenic cell that contains the same mechanisms and the same machinery to regulate circadian rhythm as all those more specialized neuronal tissues."
Scott goes on to provide greater detail on the mechanisms through which stellate calls control fibrogenic activity in a cyclical manner. When he concludes, the rest of the group shares comments. Neil Henderson notes that Circadian rhythms are strongly tied to fibrogenic processes throughout the body. Jörn Schattenberg, Louise Campbell and Rachel Zayas comment in different ways on the relevance of circadian rhythms to elements of patient care today, and Roger Green asks a question that leads Scott to note that TGF beta, which he described as "the mother of all fibrogenic cytokines," was the signaling mechanisms for this process.
Last month, roughly 5,000 liver community stakeholders gathered in London for the 2022 International Liver Congress (#ILC2022,) the first major hepatology Congress to be held in person since the start of the pandemic (smaller, but very valuable, meetings like NASH-TAG, LiverCONNECT and Paris NASH have taken place with an in-person component, but the International Liver Congress and The Liver Meeting have not). This episode focuses on an abstract session Scott Friedman chaired on Thursday afternoon discussing advancing in the basic science of researching and understanding mechanisms surrounding fibrosis.
Scott starts by describing the session he co-chaired with Sophie Lotersztajn of INSERM as "one of the most exciting groups of presentations I've seen in many years." During this episode, he leads the rest of the panel through exploration of all six presentations. These include:
--Targeting the liver circadian clock by REV-ERB-alpha activation improves liver fibrosis by circadian gating of TGF-beta signaling, Atish Mukherji, University of Strasbourg. Scott describes this presentation, which demonstrates that stellate cells have a circadian clock, as "one of the most surprising results" in that circadian activity can be linked to the "lowly stellate cell." This paper generated significant conversation among the group, ranging from Neil Henderson's observation that circadian regulation is a powerful regulator of fibrotic processes to Jörn Schattenberg's observations about what this might mean for treating patients in the clinic to Roger Green asking whether this concept might be germane to specific drugs in development (Scott had mentioned that signalling occurred through TGFbeta. Louise Campbell and Rachel Zayas add comments about the relevance of circadian rhythm to care today and ways this paper might yield exciting new areas for research.
--Stellate cell dynamics in progression and regression of hepatic fibrosis, Laura Almale del Barrio, Denmark. This presentation, funded in part by Novo Nordisk, focused on how mouse livers respond when researchers stop injuring them. It leads Neil to comment on how little attention researchers pay to scar healing relative to how much more they pay to the process of scar creation and injury. In response to a question from Scott, Neil also discusses how advances in spatial transcriptomic will make questions like these easier to research in the not-too-distant future. After this, Jörn goes on to note that the paper discussed 14 different stellate cell states, which he interprets as involves activation and transitioning processes. He asks what this might imply for treating patients in the clinic.
The other four presentations engender a similar level of exploration. They include:
--Peroxidasin deficiency re-programs macrophages toward pro-fibrolysis function and promotes collagen resolution in liver, Mozhdeh Sojoodi, Mass General Hospital and Harvard.
--Machine learning methods for detailed characterization of TGF-beta-induced signatures in a large iPSC-derived hepatic stellate cell cohort, Kara Marie Liu, Insitro, United States
--The proteomic analysis of hepatic stellate cell differentiation from iPSCs identifies RORalpha as an antifibrogenic target, Raquel A. Martinez Garcia de la Torre, Spain
--Biliary epithelial cell-specific RAGE controls ductular reaction-mediated fibrosis during cholestasis, Macrina Lam, Germany
In each case, Scott starts by discussing the historic of scientific progress that predates the particular paper and topic, places the presentation properly within that context, and invites the others to comment. Each Surfer has unique (and uniquely interesting) comments in their own areas of expertise.
Last week, roughly 5,000 liver community stakeholders gathered in London for the 2022 International Liver Congress (#ILC2022,) the first major hepatology Congress to be held in person since the start of the pandemic (smaller, but very valuable, meetings like NASH-TAG, LiverCONNECT and Paris NASH have taken place with an in-person component, but the International Liver Congress and The Liver Meeting have not). The first three days of the program focused on a range of issues, with specific emphasis on non-invasive tests (NITs) and their role at different stages in diagnosis and treatment. This conversation touches on two issues: the use of AI to better understand the meaning of liver volume and elements of morphology and, relatedly, how much more sophisticated a view we take of NAFLD and NASH than we did even five years ago.
The issues around AI and liver morphology arise from Jörn Schattenberg's comment that consistent with Stephen Harrison's "KISS" (Keep It Simple, Stupid!) principle, researchers are starting to explore the meaning of changes in liver volume. Ultimately, Jörn notes, pairing these kinds of measures with AI-supported histopathology can yield tremendous benefits. Roger comments on a breakfast he attended that morning that suggested that AI and NITs each provide different, important information on individual liver health: NITs can address collagen burden but not structure, while AI can identify changes in structure but not link them to the impact on the patient. Zobair ends this part of the conversation by noting that companies are starting to use AI in these ways.
The second part of this conversation stems from Roger's observation that we know far more about the disease than we did 3-4 years ago. He goes on to describe how the environment is more collaborative and open-minded than it might have been if, in fact, we saw drug approvals at that time. Zobair takes this observation to a different plane, noting that 5-10 years ago, "some very important experts" believed that we all understood the etiology of Fatty Liver disease, so why spend more time? He goes on, "we could not have been more wrong," observing that what we have learned about progression and regression in placebo arms suggests a far more complex disease than something that progresses linearly, or even constantly in one direction. He goes on to add that the multiple drug trial failures is that targeting drugs to a single solution based on animal models is likely to fail because this is a multiple mode of action disease. His third point: the "source" of the disease is visceral obesity and insulin resistance, which all viable solutions must address. This identifies two targets for treatment, while simultaneously demonstrating that therapy will be chronic, lifelong and with behavioral elements. The rest of the conversation addresses the challenges with shaping this kind of lifelong, multitarget therapy in the US today.
Last week, roughly 5,000 liver community stakeholders gathered in London for the 2022 International Liver Congress (#ILC2022,) the first major hepatology Congress to be held in person since the start of the pandemic (smaller, but very valuable, meetings like NASH-TAG, LiverCONNECT and Paris NASH have taken place with an in-person component, but the International Liver Congress and The Liver Meeting have not). The first three days of the program focused on a range of issues, with specific emphasis on non-invasive tests (NITs) and their role at different stages in diagnosis and treatment. This conversation touches on the impact that NAFLD has on patient quality-of-life and the importance of integrating quality-of-life issues and metrics into everything from clinical trials to treatment protocols.
This conversation starts with an observation from Jörn Schattenberg about the importance of looking more carefully at quality-of-life metrics, both in terms of patient treatment and clinical trial outcomes. MIchelle Long, making a closing comment, notes how much more collaborative researchers in the meeting are compared to years past. She then makes an announcement about a major, exciting change in her career, and then exits the conversation.
Zobair Younossi identifies "fatigue" as the patient-reported outcome from NAFLD that links most closely to quality-of-life issues He points out that fatigued Fatty Liver patients produce lower quality-of-life scores and also exhibit higher levels of mortality. He goes on to note that fatigue is also linked to unemployment and underemployment, which means that it has clear economic costs. Roger Green asks whether payers will accept economic analysis on this and, as a result, pay for therapy. Zobair suggests that this will depend on whether advocates can make this issue part of the policy, which will drive individual payers' behavior in the US and shape government policy elsewhere. In response to a question from Roger, Louise Campbell comments that the policy environment in the UK is not very different from the US despite differences in how care is actually paid for. She goes on to identify one challenge in this issue, which is that quality-of-life scores decline as soon as a patient becomes aware of their disease, which has the potential to complicate employee analyses when the employee is not yet a patient. She also agrees with Zobair's earlier statement that he would prescribe a slightly more expensive medication if it improves quality-of-life. Zobair closes this conversation by returning to discuss the importance of fatigue and describing himself as "heartened" that fatigue is now measured in most (if not all) clinical trials.
Last week, roughly 5,000 liver community stakeholders gathered in London for the 2022 International Liver Congress (#ILC2022,) the first major hepatology Congress to be held in person since the start of the pandemic (smaller, but very valuable, meetings like NASH-TAG, LiverCONNECT and Paris NASH have taken place with an in-person component, but the International Liver Congress and The Liver Meeting have not). The first three days of the program focused on a range of issues, with specific emphasis on non-invasive tests (NITs) and their role at different stages in diagnosis and treatment. This conversation touches on two issues: how proper use and explanation of NITs can increase patient motivation and why adding NITs to quality measures can have such an effect on educating providers and increasing treatment.
This conversation starts with Michelle Long and Louise Campbell discussing studies that demonstrated that patients receiving a FibroScan changed behaviors in ways that lasted at least six months, whether or not they learned they had liver fat. From here, Zobair Younossi discusses the importance of front-line, primary care screening with FIB-4 for all patients with diabetes. Zobair suggests that we consider making use of FIB-4 as a test for co-morbidities in diabetes a formal quality measure, in the same way that providers are required to check creatinine to assess possible kidney damage. Michelle and Roger Green added to Zobair's comment to discuss the specific benefits of adding an electronic health record-generated FIB-4 test as a standard assessment for diabetic patients. Zobair goes back to the point that we need primary care to serve as a front line for diabetes testing. In this context, he suggests the importance of FIB-4 and gives reasons he believes FibroScan will never become widely used in primary care. Louise Campbell disagreed, saying that having FibroScan in primary care would educate patients and drive better care. Jörn Schattenberg discusses some sessions where the consensus supported early FIB-4 use. Roger Green wraps up this conversation by talking about the importance of having formal quality measures around FIB-4 use in the US by telling a story from his own medical history.
Last week, roughly 5,000 liver community stakeholders gathered in London for the 2022 International Liver Congress (#ILC2022,) the first major hepatology Congress to be held in person since the start of the pandemic (smaller, but very valuable, meetings like NASH-TAG, LiverCONNECT and Paris NASH have taken place with an in-person component, but the International Liver Congress and The Liver Meeting have not). On the last full day of the program, several vitally important drug development studies were presented during the late-breaker and dedicated sessions. The conversations in this episode will review some of the most important findings. This particular conversation focuses on the semaglutide cirrhosis late-breaker and, more broadly, what panelists consider the presentation from this Congress most likely to effect change over the next 2-3 years.
Because Stephen Harrison needs to depart, the episode starts with him answering a question about the most consequential paper in the Congress. He focuses on the resmetirom late-breaker, which presages potential drug approval within the next 18 months. Jörn Schattenberg takes a different tack, identifying the semaglutide cirrhosis late-breaker instead. Jörn notes that the study did not achieve its primary endpoint of 1-level fibrosis reduction in 48 weeks, but cites other studies and experiences to suggest this is very, very hard to achieve for any drug. Jörn continued to suggest that semaglutide's safety level combined with the ability to help patients lose weight and reduce their HbA1c levels means this can be a valuable drug for Fatty Liver patients as well as diabetics and people with obesity, the currently indicated patient populations.
From here, the group provides answers to the "most consequential presentation" question and the conversation comes to an end.
During last week's #ILC2022 meeting in London, Louise Campbell took the opportunity to sit down with PBC Foundation CEO and Fatty Liver patient Robert Mitchell-Thain to discuss patient engagement from their own perspectives, Louise as a longtime hepatology nurse and Robert as a patient advocate and NAFLD patient.
Robert starts by discussing his own experience with Fatty Liver disease. First, he notes the importance of patients boldly defining themselves as patients and taking ownership of the word "Patient." As he notes, doctors are only involved with patients during brief, infrequent office visits while patients themselves live the part every day when making a range of decisions about their healthy (or not so healthy) lives.
Louise describes her excitement at seeing the data the British Liver Trust, Echosens and e-Scopics have collected while testing people at the meeting. She goes on to mention data from the MAESTRO NAFLD-1 trial, where patients skipped an average of two months of doses due to logistics related to the COVID-19 pandemic, but still showed clinical benefit. Sharing that kind of data with patients might make them feel more comfortable resuming medication after one (or a few) missed doses.
Robert goes on to discuss his own "day of diagnosis"...his reaction to the suggestion about losing 10-15% of his body weight and his recognition that the patient's urge at a moment like that is to "fight or flight." He goes on to note that this kind of emotional response is not solution-oriented so that patients and providers alike would do well to consider revisiting how to achieve goals like 10% weight loss at a more rational moment when the patient can focus on solutions. (Robert reminds us that from the moment the patient receives a diagnosis until they leave the physician's office, they fail to retain 40-70% of what they have been told.)
In the end, Robert would like to see more patient experience and patient involvement presentations next year, while Louise hopes for a successful NASH drug Phase 3 study that might point the way toward approval. They go on to discuss some issues around PBC before wrapping up the conversation.
During last week's #ILC2022 meeting in London, Louise Campbell took the opportunity to sit down with PBC Foundation CEO and Fatty Liver patient Robert Mitchell-Thain to discuss patient engagement from their own perspectives, Louise as a longtime hepatology nurse (and NAFLD nurse) and Robert as a patient advocate and NAFLD patient.
In this conversation, Louise and Robert start by discussing items that have "rocked their world" from this meeting. Robert starts by commenting on presentations that suggest how many patients get missed with a FIB-4 or ALT and expresses the hope that we will improve screening processes to find more people quickly. From there, the conversation shifts toward the role of stigma in patient communication. Specifically, Robert notes about "internal" stigma, the discomfort that patients have discussing their own issues of weight and appearance or sexual dysfunction. Specifically, he states that patients need to "lead from the front" by bringing the statements out in the open, which will make it more obvious that physicians and nurses need to raise these issues during initial visits. It will also push these issues into clinical trials, where we can learn about frequency. Robert notes that nurses have unique value: physicians care about metrics and medical numbers, patients care about quality-of-life, and nurses has the knowledge and skills to bridge between the two. In closing, both agree that patients need to be bold and up-front about their issues instead of, as Louise notes, surrending all accountability once a person allows herself to be define as a patient.
Last week, roughly 5,000 liver community stakeholders gathered in London for the 2022 International Liver Congress (#ILC2022,) the first major hepatology Congress to be held in person since the start of the pandemic (smaller, but very valuable, meetings like NASH-TAG, LiverCONNECT and Paris NASH have taken place with an in-person component, but the International Liver Congress and The Liver Meeting have not). On the last full day of the program, several vitally important drug development studies were presented during the late-breaker and dedicated sessions. The conversations in this episode will review some of the most important findings. This particular conversation focuses largely on Stephen Harrison's presentation of results of a Phase 1 trial for pemvidutide, a dual GLP-1/glucagon agonist, at this meeting.
The conversation starts with a brief discussion about the appropriate context for using and interpreting FIB-4 results. The closing comment for this discussion comes from Michelle Long, who suggests that use of FIB-4 is context-sensitive: "You have to know what's your question and how are you thinking of using this test" because its usefulness changes depending on the disease prevalence in the population being studied.
From here, Stephen starts to discuss a Phase 1 trial for pemvidutide that he presented at #ILC2022. Of the 34 patients in this trial, 8 had fat in their livers; all were overweight or obese. Stephen describes the GLP_1/glucagon combination as being like "not eating and exercising at the same time" because GLP-1s work on satiety control and gastric emptying (not eating) while glucagon increases overall metabolism and specifically revs up lipid metabolism (exercise) "because you're cutting the intake of calories [while] increasing the burn rate through the liver. He goes on to note the reason that by lowering Cmax and increasing Tmax, it demonstrates the pharmacokinetic profile of a q1w drug. Of the 8 patients with measurable liver fat, all dropped below the level of detection at the 1.8 and 2.4 doses (representing a 90% reduction). Stephen closes his discussion of the trial by mentioning dramatic weight loss levels and a 14-15% drop in liver volume over 12 weeks.
All the panelists express positive reactions to these results. In response to a question from Roger, Mazen says they are as good as endo-bariatric surgery or better. As the conversation ends, Mazen goes on to ask whether this is an acute or maintenance medication and states he suspects it will be lifetime maintenance.
Last week, roughly 5,000 liver community stakeholders gathered in London for the 2022 International Liver Congress (#ILC2022,) the first major hepatology Congress to be held in person since the start of the pandemic (smaller, but very valuable, meetings like NASH-TAG, LiverCONNECT and Paris NASH have taken place with an in-person component, but the International Liver Congress and The Liver Meeting have not). On the last full day of the program, several vitally important drug development studies were presented during the late-breaker and dedicated sessions. The conversations in this episode will review some of the most important findings. This particular conversation includes reactions to the two major resmetirom presentations from the rest of our panel.
It starts with Jörn Schattenberg responding to the spleen and liver volume statements in Stephen's presentation. He signals partial agreement and acceptance, then goes on to comment on ways the study methodology might have led to clearer volume data to interpret. In the end, though, he notes that other papers have linked spleen volume to clinically significant changes in portal hypertension. Stephen acknowledges Jörn's comments and suggests that the upcoming MAESTRO Outcomes study might be an excellent place to resolve these issues.
Mazen Noureddin provides a more upbeat assessment of this data. He notes that when treating patients, the positive signs he seeks are reduction in spleen size and liver volume accompanied by a change in platelets. Since all three of these occurred in the cirrhotic cohort, he is somewhat optimistic about what future studies will prove. On the MAESTRO NAFLD-1 Phase 3, he states that this is the first trial he can recall (perhaps the first, period) where MRE is reduced. He "hopes this is fibrosis" and is excitedly awaiting confirmation when biopsy results are released.
Michelle Long agrees with Mazen and further notes that in the non-cirrhotic trial, the idea that patients missed two months of doses made the results more "generalizable" to what we might expect in standard clinical practice. Louise Campbell follows this up with the statement that many MAESTRO NAFLD-1 patients will likely be referred back to primary care for treatment and expresses her confidence that resmetirom might be a good option for PCPs when treating these patients.
The rest of the season focused on issues of biomarker inaccuracy. Jörn shares results from a presentation by Jerome Boursier on the accuracy of FIB-4 in Type 2 Diabetes patients and an analysis of the MAESTRO NAFLD-1 data he presented. In his presentation, 26% of patients with NAS >= 4 and biopsy-confirmed F2 or F3 NASH had normal ALT scores, and 80% had ALTs less than 2x normal. In Germany, where ALT is the test PCPs conduct before referring patients, Jörn expressed concerns about how many patients needing treatment are missed due to false ALT negatives. The rest of the discussion centers around defining the proper use of FIB-4 and areas with vast potential for misuse.
Last week, roughly 5,000 liver community stakeholders gathered in London for the 2022 International Liver Congress (#ILC2022,) the first major hepatology Congress to be held in person since the start of the pandemic (smaller, but very valuable, meetings like NASH-TAG, LiverCONNECT and Paris NASH have taken place with an in-person component, but the International Liver Congress and The Liver Meeting have not). On the last full day of the program, several vitally important drug development studies were presented during the late-breaker and dedicated sessions. The conversations in this episode will review some of the most important findings. This particular conversation discusses two presentations on resmetirom, the late-breaker safety results (and some preliminary, secondary efficacy markets) from the Phase 3 MAESTRO NAFLD-1 trial, and a separate study looking at 180 cirrhotic patients in the open-label cohort of MAESTRO.
MAESTRO NAFLD-1 was a double-blind, randomized, placebo-controlled trial of 80 or 100 milligrams of resmetirom versus placebo, with close to 1,200 patients in these three cohorts. There was a fourth 100mg open-label cohort as well, with 180 cirrhotic patients among the trial population. For MAESTRO NAFLD-1, the primary endpoint was safety. In addition, there were several key secondary endpoints, including pathogenic lipids, and certain MRI characteristics, along with FibroScan (both KAP and KPA). To primary author Harrison, the "take-home point" from this study was "there was no bad news from MAESTRO NAFLD-1, and it did meet its primary endpoint with all the key secondary endpoints under hierarchical control having statistical significance as well.
One more interesting point from this presentation. Because the study was fielded during the COVID-19 pandemic, patients in the three closed-label arms missed an average of two months of doses due to pandemic-related logistical challenges. Despite this, the secondary endpoints demonstrated efficacy, although some demonstrated reduced efficacy compared to what we would expect from a full course of therapy.
Stephen then shares significant data from the first 105 patients in the open-label cirrhosis group. Without going into detail, the "take-home point" here is that "in addition to the safety and tolerability... we were moving noninvasive tests in a way that made us feel like something positive was happening relative to maybe some early portal hypotensive changes." Stephen notes the caveat that the researchers performed neither endoscopy nor HPG measurements in this population.
Last week, roughly 5,000 hepatology stakeholders met at the ExCel Centre in London for #ILC2022, the first major hepatology Congress with significant in-person attendance since the start of the COVID-19 pandemic. This wrap-up episode covers some of the major drug development and patient screening themes that emerged from ILC.
The previous ILC2022 episodes spent virtually no time on NASH drug development, so moderator Roger Green starts by suggesting this episode pay specific attention to the medications covered in the late-breaker session and Friday press conference. Stephen Harrison, who presented the resmetirom late-breaker and two other resmetirom studies at the conference, started by talking about the resmetirom late-breaker, which reported initial Phase 3 results from the MAESTRO NAFLD-1 trial. The trial's primary endpoint was safety, with several secondary metabolic endpoints. Stephen describes the drug as "safe and well-tolerated in over 1200 patients treated for one year with 80mg or 100mg versus placebo." On the secondary endpoints, there were "statistically significant reductions in anthropogenic lipids, LDL, APO B ,triglycerides , lipo A" and MRI- PDFF. Also, Stephen notes that because this study took place at the height of the COVID-19 pandemic, patients in the 80mg, 100mg and placebo cohorts missed an average of two months of doses over a 12-month study. Despite this challenge, the drug showed significant effects in MRI-PDFF and MRE. All told, Stephen sees "no bad news" in MAESTRO NAFLD-1.
He shifts focus to the cirrhotic study. Resmetirom was safe and well-tolerated in this population and, non-invasive tests moved in a way that suggested possible movement on early portal hypertensive changes. Stephen notes that the upcoming MAESTRO Outcomes study will allow researchers to learn whether the pathophysiologic changes are linked to outcomes. Mazen and Jörn make generally supportive comments.
Michelle picks up by describing the late-breaker as "generalizable." As she notes, most patients in practice miss doses, which makes these results more akin to real practice. Louise reads this data to say that even in primary care, patients can improve if screened and treated properly.
Jörn takes lead to review the accuracy of biomarkers, specifically ALT and FIB-4. He discusses his presentation based on 2000 liver biopsied patients in the MAESTRO NAFLD-1 population. Of these advanced patients, 26% had normal ALT levels and 80% had ALT levels less than 2x normal. Jörn makes the point that we must find ways not to miss these patients when they appear in hepatology practices since cannot rely on ALT, or even FIB-4, to identify significant disease.
Stephen moves on to discuss the dual GLP-1/glucagon agonist pemvidutide. The pemvidutide study is a Phase 1 with 34 patients focusing on safety and pharmacokinetics. He comments that atherogenic lipids were reduced more than with standard weight loss, points out highly promising results around liver fat, mentions a 14-15% drop in liver volume over 6 weeks and notes a highly tolerable safety/side effect profile. Mazen notes how remarkable he found it that after 12 weeks, 100% of patients on the 1.8mg dose achieved 5% weight loss and 55% achieved 10%.
Jörn shifts the conversation to discuss the semaglutide late-breaker. While semaglutide showed no efficacy in reducing fibrosis for cirrhotic patients over a 48-week period, the group saw positive signs in sema's high level of safety coupled with the ability to meet secondary goals: weight loss, HbA1c reduction. Michelle suggested that this study and others like it might give hepatologists comfort in prescribing GLP-1 today for obese or diabetic patients with NAFLD or NASH. Louise mentions a statin presentation she attended with a similar message about the benefit of non-NASH drugs against targets that matter to NASH patients.
The International Liver Congress (#ILC2022) is the first major hepatology Congress to be held in person since the start of the pandemic (smaller, but very valuable, meetings like NASH-TAG, LiverCONNECT and Paris HASH have taken place with an in-person component, but the International Liver Congress and The Liver Meeting have not).
The conversation takes place against the schedule of a live Congress on the day that focused on drug development. This presented scheduling challenges, which Louise Campbell addressed by combining two shorter conversations.
The first conversation included Jörn Schattenberg, Mazen Noureddin and Ian Rowe and focused on a morning session titled "NAFLD: Diagnostics and non-invasive assessment." This conversation focused on several elements of this session: papers demonstrating the relative lessons and values of FAST, MAST and MEFIB, an analysis from the LITMUS Metacohort identifying the combination of metrics that did the best jobs of specifically predicting fibrosis, steatosis, ballooning and inflammation, and papers looking at the ability of FIB-4 to identify at-risk patients. The most important conclusions: (i) the LITMUS presentation attempted to correlate to biopsy, which is a suboptimal target; researchers should consider the limitations of biopsy in planning future trials; and (ii) many tests have significant value as long as we use them properly with an appreciation of what the test seeks to determine and why for that purpose, one test might be better or weaker than others.
As this conversation winds down, Louise Campbell discusses interpretive challenges caused by the fact that studies do not list the generations of technology researchers use. She points out specifically that successive generations of FibroScan demonstrate significant differences in terms of tools that are available and the reliability of different tools.
Finally, Jörn discusses a study in the Public Health session from the SEAL program suggesting that roughly half the patients never return for their second visits. After this, Mazen asks Jörn to discuss his presentation in the NAFLD Diagnostics session. Jörn presented results of a MAESTRO-NASH analysis in which the researchers assessed the ability of FIB-4 to identify and diagnose at-risk F2 and F3 patients from among a 2,000 patient cohort. Key point: 37% of patients in this trial had normal ALT and 80% had <2x normal ALT. The second finding was that FIB-4 with a cutoff of 1.3 will miss a significant number of at-risk patients defined by F2 and F3. In this session, Jerome Boursier presented a study with a similar finding for diabetic patients. Louise mentioned a presentation from Rohit Loomba that made similar points with cirrhotic patients.
With this, the episode shifts to Louise's interview with Robert Mitchell-Thain, CEO of the PBC Foundation and long-time patient advocate with The Global Liver Institute. Robert commends the "really holistic, complete" agenda that, from a patient perspective, "really sets the standard of where we need to go in the future." He advocates bringing more patient perspectives into symposia and other events and programs. In response to Louise, Robert highlights several items that "rocked his world": the number of patients whose disease is missed when we rely on a FIB-4 test as the sole screening tool; the importance of bringing patients into the disease discussion early in the course of the disease. From here Louise and Robert go on to discuss the roles of doctors, nurses, other professionals and patients in maintaining an open discussion of the real-world challenges of therapy. They focus on two pertinent, realistic challenges: sexual dysfunction and physical appearance. Words cannot do this conversation justice...you will simply have to listen.
The International Liver Congress (#ILC2022) is the first major hepatology Congress to be held in person since the start of the pandemic (smaller, but very valuable, meetings like NASH-TAG, LiverCONNECT and Paris HASH have taken place with an in-person component, but the International Liver Congress and The Liver Meeting have not).
The conversation takes place against the backdrop of a live Congress, which means background noise, challenges finding a meeting location and more background noise than you will find during a studio episode.
Once everyone had settled in, this episode covered a range of topics, the most important of which revolved around the value of FIB-4 and the need for integrated, strategic thinking about care. The FIB-4 discussion addressed both strengths and weaknesses of the test, which is inexpensive and produces a relatively high level of false-positive tests. One key point from both Zobair and Michelle: in the US, the quality and standards organizations such as NCQA and HEDIS, should include FIB-4 screening and automatic EHR inclusion as a quality criterion with a point value in the scoring criteria. The discussion allowed the group to discuss several other important issues from the day's events. There was limited discussion of drug trials since most of the major trials will be presented on Saturday. Listen to Episodes 33 and 34 for more feedback on those presentations.
At the end of the session, Michelle Long announced that she is leaving academia in July to join Novo Nordisk and get involved full-time in helping her new employer develop good drugs and shape overall treatment paradigms and pathways.
This episode is sponsored by DiaPharma. DiaPharma is proud to support Surfing the NASH Tsunami in its activities to raise awareness of, and foster discussions about, the NASH epidemic. DiaPharma offers noninvasive mechanistic biomarkers, like CK18, that provide early biologically plausible indications of changes in disease activity for use in NASH drug development studies. For research use only, In the US and Canada, and not for use in diagnostic procedures.
Next week, >10,000 Fatty Liver stakeholders are expected to journey to London (rail strike and all) for the International Liver Congress (#ILC2022), the first meeting at this level since the pandemic started to include an in-person attendance option. This week, NASH Tsunami identifies some of the most important and intriguing non-embargoed presentations at #ILC2022. This conversation focuses largely on OS025 Non-invasive fibrosis scores as prognostic biomarkers of liver events, cardiovascular events and all-cause mortality in people with obesity and/or type 2 diabetes in the UK: a longitudinal cohort study, from Quentin Anstee (UK).
Stephen introduces this paper as one he found exceptionally important. He points out that the link from FIB-4 to major liver-associated outcomes (MALO) is not particularly novel, but the effort to link FIB-4 scores to MACE (cardiovascular events) and all-cause mortality is unique. In this case, the study tracked >45,000 patients with obesity or Type 2 diabetes plus a fibrosis score of F1 or higher for a ten-year period, over which time they observed almost 1,000 liver events, all either cirrhosis or events tied to cirrhosis. When tabulating these events against FIB-4 level, the researchers found 1% in the "low" group (FIB-4 2.45).
The picture changes in interesting ways when looking at CVD and all-cause mortality. The percentages for CVD mortality were 11% for low, 27% for intermediate and 33% for high. For all-cause mortality, the numbers were 13%, 37% and 61% respectively. Stephen notes that FIB-4 looks like a more valuable test when measured against real-world endpoints instead of biopsy, which he describes as the "bronze standard."
Roger joins the conversation to look at these results from a primary care patient screening perspective. He notes that for CVD mortality, the indeterminate score was almost as good as high for predicting 10-year outcomes, and it was significantly better than the low score for all-cause mortality. He suggests that these numbers provide a strong case for integrating FIB-4 into primary screening for all obese or diabetic patients, as some guidelines are beginning to recommend.
Louise goes on to consider the 10-year outcomes in the context of how much juvenile obesity and Type 2 diabetes we are beginning to see in population assessments and suggests that there results forebode declines in longevity, health and quality-of-life in the years to come.
After Stephen notes that there are some excellent clinical trial presentations in #ILC2022 (but these are embargoed), each Surfer picks one session that intrigues them. Stephen looks at the Wednesday morning "think tank" titled "Think Tank on Risk Stratification and Drug Development." Jörn selects the Friday morning joint EASL-EASD session titled "One or many fatty liver diseases? Clinical impact of disease heterogeneity." Louise selects Saturday's Public Health session and Roger selects an abstract session from Saturday morning titled, "NAFLD: Diagnostics and non-invasive assessment."
Next week, >10,000 Fatty Liver stakeholders are expected to journey to London (rail strike and all) for the International Liver Congress (#ILC2022), the first meeting at this level since the pandemic started to include an in-person attendance option. This week, NASH Tsunami identifies some of the most important and intriguing non-embargoed presentations at #ILC2022. This conversation continues our discussion of OS044, NAFLD patients have worse health-related QoL compared to the general population irrespective of their fibrosis stage: results from a prospective multicenter UK study, from Margarita Papatheodoridi (UK) and discusses THU051, Health-related quality of life is impaired in people living with HIV and hepatic steatosis, from Maurice Michel (DE).
This conversation starts by picking up on the far-ranging discussion of quality-of-life that ends Episod 30.2. It starts with Roger making two points: one about the impact that clinician/clinical trial design consultants can have on bringing quality-of-life endpoints to a more central role in Phase 3 trials and another that drug revenue forecasts might grow if forecasters integrate the impact of quality-of-life metrics into the target patient population. Louise notes the secondary impact of quality-of-life of work days lost and quality of work time. Jörn mentions THU051, a paper from his group that focuses on similar quality-of-life issues in patients with NAFLD living with HIV as well.
Next week, >10,000 Fatty Liver stakeholders are expected to journey to London (rail strike and all) for the International Liver Congress (#ILC2022), the first meeting at this level since the pandemic started to include an in-person attendance option. This week, NASH Tsunami identifies some of the most important and intriguing non-embargoed presentations at #ILC2022. This conversation explores two of these: FRI 100, Shear wave elastography, transient elastography and enhanced liver fibrosis test use in the assessment of NAFLD in real-world practices, from Zobair Younossi (US); and OS044, NAFLD patients have worse health-related QoL compared to the general population irrespective of their fibrosis stage: results from a prospective multicenter UK study, from Margarita Papatheodoridi (UK). In the middle, the Surfers briefly discuss why the balance of papers discussed in this episode tilts so strongly toward real-world data and large databases.
Louise starts this conversation by bridging from her discussion of FRI094 to another poster (FRI100) that assesses the real-world value of three different techniques for assessing NAFLD levels. She shares the paper in the context of this year's papers tilting heavily toward real-world data. In this case, the researchers utilized a database of over 13,000 respondents, reduced the size down to ~4,000 with FIB-4>1.46, and then attempted to stage patients using Electronic Health Record data and elastography (shear wave of VCTE). The paper concluded that the combination of these measures in EHR provided excellent guidance in staging without having to resort to special blood tests on the first round.
The conversation shifts briefly into the issue of how the pandemic slowed clinical drug development trials. Stephen shares his experience on where trials slowed down the most to support the idea that the pandemic is the factor driving a lower number of drug development papers and to say that this will increase in the years ahead.
From here, Roger begins his discussion of OS044, a prospective study over 561 UK patients exploring associations of fibrosis severity and metabolic comorbidities with QoL score levels. The pivotal finding of the abstract is that there is a clear significant difference between patients with and without NAFLD, and another clear difference between cirrhotic and non-cirrhotic NAFLD patients, but no significant difference between patients with NAFLD and pre-cirrhotic NASH. Roger comments that this is important for two reasons: it attests to the logic of Global Liver Institute's #StopNASHNow slogan for International NASH Day, and it strengthens the case for making Quality-of-Life an endpoint in clinical trials. Jörn comments on the rigor of the design and speculates on the degree to which diabetes might underlie these findings. Stephen closes the conversation by focusing on the importance of physicians checking patients' quality-of-life as part of their screening and regular visits, hard as it might be to find the time to ask.
Next week, >10,000 Fatty Liver stakeholders are expected to journey to London (rail strike and all) for the International Liver Congress (#ILC2022), the first meeting at this level since the pandemic started to include an in-person attendance option. This week, NASH Tsunami identifies some of the most important and intriguing non-embargoed presentations at #ILC2022. This conversation explores two of these: OS097, Machine learning algorithms identify novel biomarker combinations for NAFLD, from Jenny Lee (Netherlands); and FRI094, Clinical and economic evaluation of community-based preventative screening strategies for NAFLD in people with Type-2 diabetes melllitus, from Roberta Forlano (UK).
Jörn Schattenberg selected OS097 as the first paper for the Surfers to discuss due to its robust dataset (720 liver-biopsied patients recruited prospectively at centers across Europe; 53% with NASH, 26% with advanced fibrosis and 7% with cirrhosis.) and intriguing task (identify the most robust biomarkers for predicting levels of steatosis, ballooning, inflammation and fibrosis independently). The AUCs for fibrosis were robust (0.90 in the test group and 0.84 in the validation set), while the AUCs for the steatosis measures were weaker (0.79 and 0.74, respectively.) Jörn notes that the histological markers vary between the four targets, with steatosis and ballooning predicted most strongly by BMI, inflammation by hemoglobin and fibrosis by VCTE. After questions, Jörn goes on to note that the CK-18 M 30 emerges as a predictor for both steatosis and fibrosis.
The key question comes from Stephen, who asks how diabetes came into this equation in terms of metric, severity and length of disease. Jörn states that the only diabetes metric in the set was A1c, which was the 5th strongest for fibrosis. He also notes that length of disease is exceptionally challenging to determine in a study that relies on patient self-reports.
Louise Campbell responds next, selecting FRI094, a clinical and economic assessment of community-based screening of Type 2 diabetes mellitus patients for Fatty Liver disease. This study began at Imperial while Louise still worked there. The study reported 17% of NAFLD patients with "significant" fibrosis (kPa>8.1 by VCTE), 11% had advanced fibrosis and 3% had cirrhosis (defined as kPa >12,1 by VCTE.) Any of these patients might have been defined by clinical, radiological or histological means.
After questions, Louise would go on to note that all approaches were determine to be cost effective against a metric of 20,000 English pounds.
Again, the pivotal question came from Stephen, who suggested that a kPa of 12.1 (the definition of cirrhosis here) would fit half of his practice. He used this point to remind listeners of the poor positive predictive value of VCTE as a single measure.
When Stephen and Louise finish this point, Louise notes the positive recommendation on cost-effectivesness of community screening while acknowledging the issue around scoring of cirrhosis. Jörn then closes the discussion of this paper (and the conversation) by agreeing with Stephen's comment on the VCTE kPa and cirrhosis, but noting that the high levels indicate a serious challenge (even if not a level of cirrhosis).
This week, NASH Tsunami identifies some of the most important and intriguing presentations at next week's International Liver Congress (#ILC2022) meeting, many of which focus on NITs and patient issues, including quality of life (QoL). The group was free to discuss any presentation not under embargo, which precluded several major drug development presentations.
Here are the presentations and posters that the Surfers identified:
OS097: Machine learning algorithms identify novel biomarker combinations for NAFLD. Jörn raised this paper first based on the robustness of data and interesting approach. The dataset comes from 720 patients in the LITMUS Metacohort with biopsy-proven NAFLD. The researchers used 33 variables to build separate predictive models for advanced fibrosis (F>=3) and NAS (NAS>=4). The advanced fibrosis model was robust; its strongest predictors were liver stiffness (measured by VCTE) and CK-18 M30 antigen. The authors described the NAS model and various NAS element scores as "less impressive," with different predictors for each element. Jörn praised the presentation's granularity, which allowed separate looks at each predictor.
FRI094 -- Clinical and economic evaluation of community-based preventative screening strategies for NAFLD in people with Type-2 diabetes melllitus. Louise raised this paper as a "model of what might happen" when we broaden community screening to all Type 2 diabetes patients. While there were challenges to some study definitions, Louise noted that testing proved cost-effective virtually no matter how data were analyzed.
FRI100 -- Shear wave elastography, transient elastography and enhanced liver fibrosis test use in the assessment of NAFLD in real-world practices. Louise discussed this paper briefly to note that in a fairly large "real-world" population, FIB-4 plus shear wave elastography and VCTE provided sufficient data for a viable assessment of high-risk populations.
OS044 NAFLD patients have worse health-related QoL compared to the general population irrespective of their fibrosis stage: results from a prospective multicenter UK study. Roger identified this presentation as making a vital point about QoL metrics in NAFLD. There were significant QoL differences between cirrhotics and other NAFLD patients, and between pre-cirrhotic NAFLD patients and their matched controls, but not between NAFLD and pre-cirrhotic NASH. Jörn and Roger made follow-up points dealing, respectively, with drug trial design and possible increases in forecasters' market size estimates.
THU051 -- Health-related QoL is impaired in people living with HIV and hepatic steatosis. Jörn noted that this poster from his group in Maïnz makes similar points about NAFLD and QoL but in an HIV population. In this group, steatosis drove lower scores for mobility, pain, and discomfort. Stephen notes that the common message of the two papers is that we need to find a way for providers to discuss/query patients about QoL in their already overloaded patient visits.
OS025 Non-invasive fibrosis scores as prognostic biomarkers of liver events, cardiovascular events and all-cause mortality in people with obesity and/or type 2 diabetes in the UK: a longitudinal cohort study. This paper, which Stephen found "quite interesting," focuses on FIB-4 scores (classified as low, indeterminate, or high) in a cohort of 45,000, with 10 years of follow-up. High scores uniquely predicted liver events, while high and indeterminate scores both predicted CVD. For all-cause mortality, the three categories were spaced evenly. This study makes the real-world value of FIB-4, which can be hard to interpret when compared to biopsy, much clearer.
There is far more that we cannot fit into a 4K character description. Listen and learn.
Thursday, June 9, marked #NASHDay 2022, the 5th annual celebration of International NASH Day by the world's largest liver patient advocacy organization, the Global Liver Institute. For the #NASHDay Wrap-up Panel, Global Liver Institute invited NASH Tsunami co-hosts Jörn Schattenberg, Louise Campbell and Roger Green to join NASH Programs Director Jeff McIntyre to discuss themes of the day and major issues in the Fatty Liver community.
This conversation includes the last fifteen minutes of the GLI NASH Day wrap-up panel. Jeff McIntyre asks two questions to the group. First, he asks each panelist to respond to the slogan “#StopNASHNow and its implication that for patients, it might be enough simply to arrest the progression of fibrosis, and therefore we should devote some of our research and regulatory energy to stopping the progression instead of focusing entirely on regression. For his last substantive question, he asks each of us to discuss something that puts a twinkle in our eyes as we consider the next 3-5 years of progress in the fight against Fatty Liver disease. Great questions that yield interesting and diverse answers from the three Surfers.
Thursday, June 9, marked #NASHDay 2022, the 5th annual celebration of International NASH Day by the world's largest liver patient advocacy organization, the Global Liver Institute. For the #NASHDay Wrap-up Panel, Global Liver Institute invited NASH Tsunami co-hosts Jörn Schattenberg, Louise Campbell and Roger Green to join NASH Programs Director Jeff McIntyre to discuss themes of the day and major issues in the Fatty Liver community.
This conversation includes highlights from the first 20 minutes of the GLI NASH Day wrap-up panel. It includes Jeff McIntyre’s first two questions to the panel and responses from Jörn Schattenberg, Louise Campbell and me. Jeff’s first question was about the role and relevance of International NASH Day in 2022, and his second question was about the areas where we need patient voice to make a difference today. Not surprisingly, the three Surfers gave answers to both questions that covered different issues but complemented each other nicely.
Thursday, June 9, marked #NASHDay 2022, the 5th annual celebration of International NASH Day by the world's largest liver patient advocacy organization, the Global Liver Institute. To celebrate the occasion, Stephen Harrison joined Jörn Schattenberg, Louise Campbell and Roger Green to celebrate the event and comment on one crucial trend or event most signified what the last year has meant in the Fatty Liver community.
This conversation includes three sections:
• First, Roger discusses the Law of Unintended Consequences in the context of the FDA Complete Response Letter to Intercept Pharmaceuticals over obeticholic acid, an event that many feared would bring all momentum around Fatty Liver disease to a standstill but, two years later, has driven real bursts of creative energy and innovative problem solving centered around the disease rather than a drug.
• Second, Stephen’s and Jörn’s impassioned statements that the providers will never give up on addressing the challenges of NASH, both because, as Stephen describes, it is not in their character and because, as Jörn describes, “this disease is not going away.” As long as people are dying too young from the effects of NASH and HCC, he contends, the fight will continue.
• Finally, Roger asked the panelists for bold predictions about what will have changed before we come together a year from now to celebrate the 6th International NASH Day.
Thursday, June 9, marked #NASHDay 2022, the 5th annual celebration of International NASH Day by the world's largest liver patient advocacy organization, the Global Liver Institute. To celebrate the occasion, Stephen Harrison joined Jörn Schattenberg, Louise Campbell and Roger Green to celebrate the event and comment on one crucial trend or event most signified what the last year has meant in the Fatty Liver community.
This conversation is about collaboration. It starts with Jörn Schattenberg noting the increasing momentum for groups to work together and proceeds to explore two observations from Louise Campbell:
• One about the rapidly expanding rate of change in the development of key products with particular emphasis on NITs
• A second on the increasing momentum behind broad approaches to the NAFLD pandemic, including the expansion of patient advocacy organizations around the world to the increasing energy all the various stakeholders and medical specialties to collaborate in an integrated attack on NAFLD and NASH. She notes that this energy needs to translate to a global set of local conversations sensitive to how healthcare operates in countries and regions.
From there, Jörn notes how Louise’s prior work in Hepatitis C gives her an experience the NASH physicians will not have and Stephen lists big items with tremendous progress, momentum and potential to a crescendo.
Thursday, June 9, marked #NASHDay 2022, the 5th annual celebration of International NASH Day by the world's largest liver patient advocacy organization, the Global Liver Institute. To celebrate the occasion, Stephen Harrison joined Jörn Schattenberg, Louise Campbell and Roger Green to celebrate the event and comment on one crucial trend or event most signified what the last year has meant in the Fatty Liver community.
This conversation consists mostly of reactions from Jörn Schattenberg, Louise Campbell and Roger Green to Stephen’s initial statement, followed by other thoughts from Stephen. The other Surfers are all impressed by the trial design. In response to a comment from Roger, Stephen comments enthusiastically on the unprecedented collaboration between sponsors, academics, regulators – the entire range of stakeholders – to resolve this issue. He goes on to note other questions – for example, the name of the disease – where the community is demonstrating unparalleled collaboration. All of this, he says, is leading to a proliferation of new research so vast that no one can keep up with all of it.
There are three more points in this conversation:
• Jörn raises Quentin Anstee’s comments from Episode 26 that we need to develop a standard set of NITs to use in the evaluation process as another area where collaboration will be key
• Stephen points out that we may see our first drug approval in 2023, which will add new levels of energy and resourcing to the development and education processes
• Jörn begins to discuss his issue, which is the convergence between conferences to cover a range of issues that look past simple drug development to improve key questions from drug evaluation to clinical care pathways and inter-specialty collaboration to treat patients
Thursday, June 9, marked #NASHDay 2022, the 5th annual celebration of International NASH Day by the world's largest liver patient advocacy organization, the Global Liver Institute. To celebrate the occasion, Stephen Harrison joined Jörn Schattenberg, Louise Campbell and Roger Green to celebrate the event and comment on one crucial trend or event most signified what the last year has meant in the Fatty Liver community.
Roger's first question was for each panelist to describe a major event that took place since the 4th International NASH Day last June. Stephen Harrison answers first by discussing major advances in clinical trial design. This conversation consists of his answer.
Stephen Harrison describes two related areas where we have made what he describes as “real, granular progress in drug development” in terms of rethinking the design of Phase 3 clinical trials and endpoint assessment related to this redesign. Historically, sponsors conducted a single, very large, very long trial that sought first to achieve conditional approval based on sub-part H endpoints in fibrosis and then to achieve full approval based on outcomes developed as the initial trial group progresses to cirrhosis. The new idea is to conduct the fibrosis and cirrhosis elements in parallel, thus shortening the time to approval, simplifying endpoints and reducing the cost of the overall trial process. It is a vision of breathtaking scope…and, Stephen reports, it’s almost ready to launch.
Today, June 9, was the 5th International NASH Day (#NASHDay). Global Liver Institute (@GlobalLiver), the largest liver patient advocacy organization in the world, and 200 partner organizations held a day of education, awareness and motivation for Fatty Liver stakeholders the world around.
For its wrap-up panel, GLI invited the SurfingNASH co-host team to sit with Jeff McIntyre and review some of the day's major themes as well as major developments since the last International NASH Day. Like a typical SurfingNASH episode, there were equal parts big picture thinking, references to recent events, and laughs. Listen for a fast-paced discussion of big-picture items, most of which are different from the Episode 28 discussion.
Thursday, June 9, marks #NASHDay 2022, the 5th annual celebration of International NASH Day by the world's largest liver patient advocacy organization, the Global Liver Institute. With over 200 affiliated organizations and sponsors, many holding their own events, International NASH Day is not only a major day for education and communication, but also in a sense NASH's "New Year's Day," a moment to take stock of the last year and make resolutions for the future.
To celebrate the occasion, Stephen Harrison joined Jörn Schattenberg, Louise Campbell and Roger Green to celebrate the event and comment on one crucial trend or event most signified what the last year has meant in the Fatty Liver community.
Stephen went first, focusing on a pivotal change in Phase 3 trial design. Unti now, corporate sponsors have conducted one large Phase 3 trial with F2 and F3 NASH patients. The initial phase of the trial would include 1,000 - 1,200 patients with the goal of achieving sub-part H approval based on conditional endpoints. This trial would keep enrolling patients until there were enough patients in the trial for 4-7 years to prove an outcome-based endpoint and achieve full approval. In the new design, two trials transpire in parallel: the original trial with F2 and F3 patients and a trial with well-compensated cirrhotic patients focused solely on achieving an outcome. This design should prove easier to recruit, less expensive, and more likely to achieve outcome-based endpoints more quickly. Also, it allows the sponsor to evaluate "co-endpoints," as Stephen puts it, instead of needing to achieve dual endpoints. This way, the sponsor can succeed by achieving fibrosis improvement with only a stable NAS score or a decline in NAS score with no worsening of cirrhosis.
All three panelists expressed admiration and appreciation for the benefits of this approach. Stephen noted how many people needed to collaborate for this to come to fruition and how much more collaboration is taking place in the community.
Jörn went next, focusing on the extraordinary breadth in focus and content of pivotal conferences during the year. He mentioned the fireside chat with regulators at NASH-TAG and the broad discussions in Barcelona exploring how best to serve patients after we have a drug.
Louise focused on systems thinking, mostly related to diagnostics, focused on how best to use non-invasive methods to screen, diagnose and stage patients. What she found striking is that these discussions are taking place before drugs are approved, which suggests the possibility that shorter after we have drugs to prescribe, we will have systems and protocols to get the drugs to the patients that need them most. Louise contrasted thought development in NASH to Hep C, where the drugs came along before we knew how to find the patients.
Rounding out the group, Roger talks about the Law of Unintended Consequences and the Intercept Complete Response Letter from FDA. He recalled the initial thoughts that the failure to approve obeticholic acid would signal a perilous downturn in interest in Fatty Liver disease. Instead, he suggested, the passion of the community coupled with lack of funds led stakeholders to ask better questions and focus on more practical issues, which has led to the convergence we are seeing today.
As the conversation wound down, Stephen and Jörn noted that providers will not tolerate "No" for an answer, recalling patients who suffered from HCC and died too young.
In the end, Roger asked the group to make a bold predictions about what will happen next year, when the group gets together on the eve of International NASH Day once again to survey the past year. The predictions were bold and optimistic. You will need to listen to or view the episode to learn what they were.
On May 27 and 28, Surfing the NASH Tsunami covered the 5th Global NASH Congress, which discussed a wide range of NAFLD-related topics. This conversation includes two shorter interviews. In the first, Louise Campbell and Aged Diagnostics CEO Rachel Zayas interview Altimmune Chief Medical Officer Scott Harris about dual agonist weight loss agents. In the second, Rachel interviews Antaros Medical Vice President of Global Business Development Caleb Roberts about the increasing value of imaging in the study of Fatty Liver Disease.
In the first interview, Scott Harris discusses the value of dual receptor agonists in weight loss. He focuses on existing published studies for GLP-1 agonist semaglutide and dual GLP-1/GIP agonist tirzepatide and shares some data on pemvidutide, Altimmune’s dual receptor GLP-1/glucagon agonist. The discussion branches into other issues, including the impact of rapid weight loss on micronutrients and the concept of sarcopenic obesity.
In the second interview, Caleb Roberts discusses the relevance of imaging for researchers assessing the metabolic effects of NASH medications on the overall metabolic profile and perhaps other organ systems, notably the kidneys. He also discusses briefly some of the concepts that Antaros is developing, including PET tracers.
On May 27 and 28, Surfing the NASH Tsunami covered the 5th Global NASH Congress, which discussed a wide range of NAFLD-related topics. In this conversation, Louise Campbell interviews Julius Clinical Chief Scientific Officer Diederick (Rick) Grobbee about NAFLD screening in primary care practices as exemplified in Julius's GRIP Program.
Most of this conversation centered around the GRIP Program, an effort to screen 10,000 metabolic disease patients in 10 European countries. The program has targeted screening 1,000 patients per country in primary care practices using VCTE as the initial screening tool. Rick and Louise review the scope and goals of the project. Along the way, their conversation also covers the need to find more patients for clinical trials and how Julius Clinical anticipates GRIP addressing this need. Other topics Louise and Rick cover include the value of a FibroScan or other scanning device in motivating patients as compared to blood tests and the need to create guidelines that make medical and economic sense in primary care practices
On May 27 and 28, Surfing the NASH Tsunami covered the 5th Global NASH Congress, which discussed a wide range of NAFLD topics. In this conversation, Aged Diagnostics CEO Rachel Zayas, who attended the conference for Surfing the NASH Tsunami, interviews Madrigal Pharmaceuticals Founder, Chief Medical Officer and President of R & D Rebecca (Becky) Taub.
Becky Taub's talk at the Congress focused on some key findings from the MAESTRO Phase 2 cirrhosis arm and Phase 3 non-cirrhosis arm. In addition to sharing data about resmetirom efficacy and safety, she discussed other findings about how resmetirom affects the liver. She discusses one of these findings, the strong impact that resmetirom had on liver volume and the larger impact that resmetirom had on liver volume relative to liver fat compared to other modes of action.
From there, the conversation goes on to cover the broad range of non-invasive tests that Madrigal deployed in their trials and some of the thinking behind that decision. As the conversation winds down, Becky discusses her belief in the vital importance of patient advocacy and the upcoming International NASH Day.
On May 27 and 28, Surfing the NASH Tsunami covered the 5th Global NASH Congress, which discussed a wide range of NAFLD topics. In this conversation, Louise Campbell and Rachel Zayas, who attended the conference for Surfing the NASH Tsunami, discuss what they considered the most important and interesting presentations at the Congress.
This fast-moving conversation touches on a range of topics, each of which was a key element of at least one Congress presentation. Specific topics include (1) the importance of patient advocacy and patient presence at events like this, (2) liver science, both in terms of Sven Franque's discussion of how liver fat affects the hepatic vascular bad and Recebba Taub's presentation on the variable relationship between liver fat and liver volume, (3) the idea of transfer RNA as a therapeutic intervention instead of merely a diagnostic, (4) a new VCTE device designed to compete with FibroScan, and (5) an innovative study to evaluate the fatty liver profiles of patients with multiple metabolic diseases currently being treated in primary care practices in Europe. Louise and Rachel focus on what they consider important, challenging or controversial on each subject.
On May 27 and 28, Surfing the NASH Tsunami covered the 5th Global NASH Congress, which discussed a wide range of topics related to Fatty Liver disease. In this conversation, Louise Campbell, who attended the conference for Surfing the NASH Tsunami, discusses presentations she found of particular interest. Jörn Schattenberg and Roger Green, who did not attend, ask questions about the presentations and raise issues that come to mind as they listen.
Two major themes emerge from this conversation. The first, triggered by a presentation from e-Scopics, involved the value and use of in-office VCTE and ultrasound devices. Louise discussed what she considered the clearest benefit of the e-Scopics machine ("I could see my liver") and its major challenge, begin compared to FibroScan instead of biopsy (which makes the device, as Louise describes it, "a surrogate of a surrogate.") Roger asks whether cost or reimbursement ever came up in the context of the meeting since the cost of placing this kind of equipment in offices is likely not to prove financially viable. This leads to acknowledgment that cost never comes up in this kind of meeting, followed by Louise's description of the Tawazun model as one way to make scanning more affordable.
The second was a look at liver disease from a patient's point of view. The specific issue was liver volume. From the scientist's perspective, it might be an interesting point, but seemingly unrelated to metabolic disease and not necessarily related to hepatic complications either. As Jörn points out, liver volume is the likely source of upper right quadrant pain, which would make it an important quality-of-life issue for patients. This brings the group back to the importance of having people in the room who can advocate for patients and take the patient perspective.
On May 27 and 28, Surfing the NASH Tsunami covered the 5th Global NASH Congress, which discussed a wide range of topics related to Fatty Liver disease. In this conversation, Louise Campbell, who attended the conference for Surfing the NASH Tsunami, discusses presentations she found of particular interest. Jörn Schattenberg and Roger Green, who did not attend, ask questions about the presentations and raise issues that come to mind as they listen.
Two major themes emerge from this conversation. The first centers on Fatty Liver science, particularly liver structure. In the first keynote of the congress, Sven Franque discussed the vascular alternations even small amounts of liver fat can cause. During one of the congress's most anticipated presentations, Madrigal Pharmaceuticals Founder, Chief Medical Officer and President of R&D Rebecca Taub discussed the idea that different prospective Fatty Liver modes of action affect liver volume differently. Of specific interest, she noted that liver volume increases disproportionately to increases in liver fat. She also noted that the MAESTRO series of trials for resmetirom revealed a larger effect on liver volume than one might have predicted based solely on resmetirom's impact on liver fat levels. In the discussion, Jörn makes two key observations: (1) the liver vascular bed is unlike the vascular beds of other organs and (2) it has been reported that the impact of NASH on vasculature is different than that of liver fat from other causes.
When discussing patient advocacy, Louise notes that when she attended this meeting in 2019, there were no patient advocates involved, whereas this year, representatives from the Global Liver Institute and the European Liver Patients Association gave talks. Louise stated that the presence of patients changed the entire tone of the discussion, leading people who work with the theory of drug development and drug effects to consider what patients truly need as they listened to the various presentations.
Surfing the NASH Tsunami covered the 5th Global NASH Congress. Louise Campbell and Rachel Zayas conducted speaker interviews with executives from Madrigal Pharmaceuticals, Altimmune, Antaros Medical and Julius Clinical, and the Surfers shared reflections on meeting topics and other key Fatty Liver-related issues.
This episode blends conversations between the Surfers and "Surfer-for-a-day" and Aged Diagnostics CEO Rachel Zayas with interviews with four of the 5th Global NASH Congress attendees: Madrigal Pharmaceuticals Founder, Chief Medical Officer and President of R&D Rebecca Taub, Altimmune Chief Medical Officer Scott Harris, Julius Clinical Chief Scientific Officer Diederick Grobbe and Antaros Medical Vice President of Global Business Development Caleb Roberts.
The interviews covered a range of topics, including: (i) the need to identify Fatty Liver patients at the primary care level; (ii) the critical role patient advocates can and must play in the product development and treatment pathway processes; (iii) the relevance of advanced imaging to understanding the multiple effects of Fatty Liver Disease and drugs that treat it on renal, cardiovascular and other non-hepatic systems in the body; (iv) the importance of liver volume independent of liver fat levels in evaluating patients and therapies; and (v) prospects that future bariatric medicines might deliver long-term weight loss at levels comparable to what we expect from bariatric surgery.
The Surfers' conversations covered these topics as well, along with a review of the two keynote presentations. In one keynote, Sven Franque expanded on a topic he covered at the #INCBCN conference in Barcelona: the ability of small amounts of liver fat to cause structural changes in the liver (removing fat will reverse these). In the other, William Alawazi discussed some clinical trial design artifacts that might obfuscate or even confound trial results.
his conversation ties up some of the loose ends of the broader "stacking" issue. Quentin Anstee addresses Roger Green's earlier concern about whether stacking variables would magnify statistical error by suggesting that if the goal of stacking is to amplify a "ground truth", this should not imply greater error.
Louise Campbell asks about future prediction of placebo response, which Quentin suggests is beyond the boundaries of this approach, which Quentin suggests is better suited to interpreting results of individual trials where "stacking" can clarify indeterminate or non-significant findings. As the conversation winds down, Jörn Schattenberg suggests adding quality-of-life variables to the analytical set, which the group agrees can serve as part of a "feel, function, survive" analysis.
This conversation starts with Roger Green asking Quentin Anstee to clarify exactly what he means by "stacking" variables. Quentin's reply: multiple measures to confirm the same endpoint or result, so that the more measure achieve the target, the more confident we can be that therapy has succeeded.
Louise Campbell suggests that this kind of stacking approach might enhance our ability to assess efficacy in diverse populations, given that demographic subpopulations might differ in the way they respond to therapy. The group goes on to discuss the importance of collecting Phase 3 trial results from a broad set of NITs in order to determine the right combination of NITs to use in a stacking equation. The conversation goes on to note the need to standardize fairly quickly to improve our ability to manage the cost and predictiveness of trials and to consider what kinds of tests and metrics will work best in the stacking process.
This conversation starts with Quentin Anstee complimenting Stephen Harrison for his observation that when we analyze NASH Biomarkers, we should consider the value of sustained response separate from early OR late response.
From here, the group moves to the concept of "stacked" tests -- confirmatory results from different NITs as a way to assess efficacy in an individual clinical trial subject. The conversation takes some twists and turns, but the core concept is unique, challenging and a significant step forward in the broader discussion of how to analyze biomarkers.
This conversation starts with Quentin Anstee sharing the five key takeaways for NITs in general and NIT Best Practices he developed while preparing recent talks for the Liver Forum and the ICFL meeting in Vienna:
(1) As we have discussed on this podcast and elsewhere, trial endpoints around balloon hepatocytes are, in Quentin's words, "not sufficiently robust."
(2) Rapidly attaining response from a given test (ALT, for example) is not necessarily a guarantee of early efficacy.
(3) "Simple indirect biomarker panels like FIB-4" need to be interpreted with caution.
(4) Since we do not have a single perfect gold standard test (neither histological nor non-invasive), we should consider a standard for clinical trial assessment that is a composite of multiple different types of tests, perhaps one liquid, one physical (MRE?) and one histological.
(5) We need to develop a battery of NITs that are both applied and reported in all cases, instead of running large numbers of NITs and only reporting the ones that support the targeted medication.
This conversation goes on to focus on points #2 and #3, which touch on the relationship between early blood test results and proof of endpoint efficacy.
Quentin Anstee joins Stephen Harrison, Jörn Schattenberg, Louise Campbell and Roger Green to share recently developed insights about NITs and what the clinical trial best practices around them should be. Quentin started by offer five key takeaways from his recent talks at The Liver Forum and ICFL in Vienna:
(1) As we have discussed on this podcast and elsewhere, trial endpoints around balloon hepatocytes are, in Quentin's words, "not sufficiently robust."
(2) Rapidly attaining response from a given test (ALT, for example) is not necessarily a guarantee of early efficacy.
(3) "Simple indirect biomarker panels like FIB-4" need to be interpreted with caution.
(4) Since we do not have a single perfect gold standard test (neither histological nor non-invasive), we should consider a standard for clinical trial assessment that is a composite of multiple different types of tests, perhaps one liquid, one physical (MRE?) and one histological.
(5) We need to develop a battery of NITs that are both applied and reported in all cases, instead of running large numbers of NITs and only reporting the ones that support the targeted medication.
This stimulating set of opening comments motivates the group to dive deeply into the entire issue of how we deploy and analyze NITs. One key question is longitudinal. Quentin points out that early response to a composite test (like FIB-4) might not suggest endpoint efficacy over time. Similar to this, it also suggests that a positive 26-week result in a composite or liquid test might not mean much if the drop comes in the first couple of weeks and then maintains the lower level the next few months. This leads Stephen to suggest that researchers evaluate change at three levels: early change, late change, sustained change. It also leads to a discussion of "stacking" tests so that a respondent would need to achieve multiple successful test scores for the researcher to be confident that the patient's response is positive.
These are only a few insights from a far larger set that emerges during this discussion. Dive in for yourself to see what you find most intriguing.
This conversation is centered on Marcelo Kugelmas's portion of Madrigal's disease-focused presentation at the Chronic Liver Disease Foundation's LiverConnect meeting this past March in Scottsdale, AZ. Marcelo addresses issues of NAFLD patient screening and NASH patient management. Afterwards, he answers questions and reviews key elements of the presentation with Roger Green. Finally, Roger interviews Dr. Naim Alkhouri on the patient prevalence implications of the San Antonio Military Medical Study (2021), of which he was an author, and on the strategies, he uses to bring patients into his practice to be screened (think "Free FibroScan" for the curious.)
This episode and all its conversations are sponsored by Madrigal Pharmaceuticals. Conversations 25.5 and 25.6 are a two-part summary of Madrigal's disease-focused presentation at the recent CLDF LiverConnect meeting.
This conversation is centered on Mazen Noureddin's portion of Madrigal's disease-focused presentation at the Chronic Liver Disease Foundation's LiverConnect meeting this past March in Scottsdale, AZ. Mazen addresses issues of NAFLD Pathophysiology and NASH epidemiology, after which he answers questions and reviews key elements of the presentation with Roger Green.
This episode and all its conversations are sponsored by Madrigal Pharmaceuticals. Conversations 25.5 and 25.6 are a two-part summary of Madrigal's disease-focused presentation at the recent CLDF LiverConnect meeting.
Louise Campbell starts this discussion by citing her sources of optimism about NASH drug development: (i) the high likelihood of getting a drug to market over the next couple of years, which will lead to better education of patients and providers alike; (ii) FDA looking for more inclusion and diversity about drug trials, which will provide even more information for historically underserved populations; and (iii) in her observations and work, patients already are becoming more aware about Fatty Liver disease and the importance of treating it.
From there, the conversation turns to consider what drug development has proven already. Jörn Scattenberg notes that even if OCA never receives approval, it has proven that regression in monotherapy is possible. Roger Green expands on this thought, noting that OCA had demonstrated efficacy and resmetirom appears to have demonstrated safety in the liver. More important to him, each drug has the prospect of proving both efficacy and safety within the next year or so. Roger goes on to note that if combination therapy is to become the ultimate strategy in an environment where so many MOAs exist, this will provide continued research funding and energy for the foreseeable future.
Jörn brings Quality of Life into the discussion as an approvable endpoint of extreme interest to patients that will become the "third pillar" of drug assessment.
These comments and the answers to Roger's closing question confirm that the Surfers believe there are sound reasons to be optimistic about drug development in the mid-term and quite possibly the short-term as well.
This episode and all its conversations are sponsored by Madrigal Pharmaceuticals. Conversations 25.5 and 25.6 are a two-part summary of Madrigal's disease-focused presentation at the recent CLDF LiverConnect meeting.
This conversation is part of a broader overview of NASH drug development in 2022, led by Stephen Harrison and Jörn Schattenberg.
It starts with Louise Campbell asking whether design and management of the ongoing trials will provide sufficient granularity on matching patient types to medications or drug classes. Stephen Harrison notes that we have not paid sufficient attention to this issue historically. In fact, he notes a range of key variables we do not explore at baseline: genotype disease markers like PNPLA3, microbiome and non-Caucasian population segments, to name three. He also notes that some promising drugs have been killed because of trial design issues. In the end, he returns to core positive concepts: combination therapies, looking for agents with multiple positive metabolic effects and safety.
At this point in the conversation, Stephen's transmission starts to fail. Eventually, he leaves the conversation and focus shifts to cirrhosis.
This episode and all its conversations are sponsored by Madrigal Pharmaceuticals. Conversations 25.5 and 25.6 are a two-part summary of Madrigal's disease-focused presentation at the recent CLDF LiverConnect meeting.
This conversation is part of a broader overview of NASH drug development in 2022, led by Stephen Harrison and Jörn Schattenberg.
It starts with Jörn commenting on the exceptional scope of opportunities for deep data dives and new learning, which becomes a lead-in for him to ask Stephen about the scope of data available from Intercept. From there, the group explores a range of issues the data might address. Among the key points: safety and tolerability are extremely important to FDA, the idea that the optimal NASH drug will also have an impact on the range of metabolic disease issues, and the long-term importance of combination therapy.
This episode and all its conversations are sponsored by Madrigal Pharmaceuticals. Conversations 25.5 and 25.6 are a two-part summary of Madrigal's disease-focused presentation at the recent CLDF LiverConnect meeting.
This conversation is part of a broader overview of NASH drug development in 2022, led by Stephen Harrison and Jörn Schattenberg.
Stephen starts this conversation by noting that the mechanics of the drug development pathway, which we discussed earlier this year in the context of NASH-TAG and strategies on how to shift away from traditional metrics, remain what they have been: same conditional endpoints (fibrosis improvement without worsening NASH or NASH resolution without worsening fibrosis, or improving both) and the same need for biopsy read as is has been. In this context, Stephen explains the difference between dual primary endpoints and co-primary endpoints in the context of a recent announcement from Madrigal.
From there, he goes on to list the various drugs and modes of action in different stages of development, starting with the five agents in Phase 3, then working his way back through the Phase 2b studies to discuss some of the more significant or interesting agents earlier in development.
This episode and all its conversations are sponsored by Madrigal Pharmaceuticals. Conversations 25.5 and 25.6 are a two-part summary of Madrigal's disease-focused presentation at the recent CLDF LiverConnect meeting.
This week, NASH Tsunami responds to listeners who have asked "Where are the episodes on drug development?" by asking Stephen Harrison to lead a review of the NASH pipeline.
Stephen starts by noting that the mechanics of the drug development pathway, which we discussed earlier this year in the context of NASH-TAG and strategies on how to shift away from traditional metrics, remain what they have been: same conditional endpoints (fibrosis improvement without worsening NASH or NASH resolution without worsening fibrosis, or improving both) and the same need for biopsy read as is has been. Stephen explains the difference between dual primary endpoints and co-primary endpoints in the context of a recent announcement from Madrigal.
From there, he goes on to list the various drugs and modes of action in different stages of development, starting with the five agents in Phase 3, then working his way back through the Phase 2b studies to discuss some of the more significant or interesting agents earlier in development.
One interesting point Stephen raises is that clinical development for obeticholic acid, the Intercept drug that FDA failed to approve, continues. By now, he notes we have data on over 2,000 patients and a significant number of patients that have been studied for over four years. Jörn Schattenberg registers his excitement at the size of this population and the wealth of data they offer researchers. Throughout this discussion of ongoing research, including not only Intercept but the length of some of the resmetirom studies, Stephen notes that NASH drug development is very much a work in process.
Led by Stephen, the group goes on to consider what our failures to date have taught us about doing drug development better, a phenomenon that Stephen, Jörn and Louise all note makes them hopeful for the future. Stephen specifically notes that drug developers and researchers alike have broadened their ambitions from simply reducing fibrosis and liver fat to being part of a total metabolic solution that includes diabetes, obesity and cardiovascular health along with liver. Before leaving the conversation, Stephen notes the critical need to improvement diversity of clinical trial populations and notes that while it may take some years, he sees the future of patient treatment as lying in combination therapy.
After Stephen leaves, the discussion shifts slightly, with more focus on cirrhosis, the reasons for drug development and increasing optimism that the drug development community is on the right path. Toward the end, the discussion turns to consider quality of life, which if affected negatively by Fatty Liver disease. Jörn notes that it could serve as the third leg of a stool or tripod to pull NASH drugs over the line. Roger suggests the possibility that a lot of antidepressants are being prescribed for patients who would feel better with less fatty livers. On that optimistic note, the group provides final answers about the most striking part of the episode and departs to live another week.
This episode is sponsored by Madrigal Pharmaceuticals. Today's extra-sode is a summary of Madrigal's disease-focused presentation at the recent CLDF LiverConnect meeting.
One of the most intriguing presentations at this month's inaugural Innovations in NAFLD Care 2022 conference (#INCBCN) came from physician, author and entrepreneur Dr. Marcus Ranney. In this conversation, Roger Green interviews Marcus on his experiences unique vision and the future of #biohacking.
In this conversation, Marcus discusses his own "journey of figuring out...how to augment [his] own health." He describes his personal history and career, how he came to write the best-selling book "At the Human Edge," to begin his Human Edge consultancy and to begin developing the #biohacking app Mito (which is still in development). Along the way, we learn about his long-standing passion for mitochondria and the ways experiencing long-haul COVID-19 has affected his health and perspective. From a market perspective, he discussed the rapid growth of technologies designed to collect and share information about the individual's metabolism.
From the platform of understanding Human Edge and mito, the dialogue veers into broader social issues. Roger discusses how the conference presented and amplified four very different views of power and control in managing individuals' health. Marcus shares his view that if we are to address social developmental needs and goals necessary to advance health, data -- at all levels -- will be key to formulating, evaluating and improving strategies and programs. These ideas do not sound radical in their one-sentence summaries, but the discussion is richer, farther reaching and more powerful than the summaries themselves suggest.
On May 6 and 7, over 100 NAFLD stakeholders convened in Barcelona and on-line for the inaugural Innovations in NAFLD Care 2022 conference (#INCBCN.) Surfing the NASH Tsunami was there, with Jörn Schattenberg serving as event co-founder and Louise Campbell and Roger Green moderating sessions. This week's episode is less a formal recap of the meeting than recollections of key moments and messages from the co-founders and Surfers.
This conversation wraps up the Surfers' discussion of the conference. The co-hosts start with comments about pharma partners' and patient advocates' favorable reactions to the meeting and go on to review many of the individual presentations. Louise shifts the focus of the conversation to the role of liver in overall metabolic wellness. Jörn notes that hepatologists are less likely to focus on liver fat as compared to fibrosis and agrees that broader focus on liver fat is important in the overall issue of metabolic health. The conversation ends with the group considering actions that might strengthen a successful 2022 conference when it recurs in 2023.
On May 6 and 7, over 100 NAFLD stakeholders convened in Barcelona and on-line for the inaugural Innovations in NAFLD Care 2022 conference (#INCBCN.) Surfing the NASH Tsunami was there, with Jörn Schattenberg serving as event co-founder and Louise Campbell and Roger Green moderating sessions. This week's episode is less a formal recap of the meeting than recollections of key moments and messages from the co-founders and Surfers. Serious comments about meeting design and the importance of stakeholder diversity are interspersed with the conference's lighter moments, in this case referring to Louise being pressed into co-chair services at the last moment.
This conversation starts with the three regular hosts describing the one memory from the weekend that will last the longest for them. Jörn discusses the intensity of the dialogues between stakeholders. Louise focuses on Cyrielle Caussy's presentation on the "fatal triple" of metabolic diseases. Roger identifies two: the passion of the patient advocates and the differences in perspective between traditional top-down, command-and-control specialist medicine as compared to data-driven patient empowerment as depicted by Marcus Ranney's Mito app in development. Given the focus on diverse stakeholders throughout the meeting, the conversation shifts to focus on stakeholders who were NOT well represented: nurses for one, payers and regulators for another. As a final comment, Louise mentions the consistency of a meeting where every presentation, every session was enlightening and satisfying.
On May 6 and 7, over 100 NAFLD stakeholders convened in Barcelona and on-line for the inaugural Innovations in NAFLD Care 2022 conference (#INCBCN.) Surfing the NASH Tsunami was there, with Jörn Schattenberg serving as event co-founder and Louise Campbell and Roger Green moderating sessions. This week's episode is less a formal recap of the meeting than recollections of key moments and messages from the co-founders and Surfers.
While the question in this conversation comes from Roger Green, who asks about controversies, the two pivotal controversies center around views of patient empowerment. The conversation begins where the last one ended, which Louise Campbell and Roger Green commenting that calling the entire disease class simply "Fatty Liver Disease," as proposed by Primary Care participant @Jean Mareis, would remove a controversial issue and foster stronger communication between doctor and patient. In response, Jeff Lazarus and Jörn Schattenberg note that there is an ongoing delphi exercise led by Jeff and his team, which will report on July 8 and 9. From here, the discussion around controversy shifts focus to the varying reactions to #HumanEdge founder Marcus Ranney's presenting about #biohacking and his developmental Mito app. Questions ranged from how much data to put in patients' hands to where analysis should be controlled. This element wraps up with Jörn Schattenberg noting the research value of the data that Human Edge proposes to collect. The last part of this conversation covers plans for the 2023 conference and congratulates Jeff as he departs.
On May 6 and 7, over 100 NAFLD stakeholders convened in Barcelona and on-line for the inaugural Innovations in NAFLD Care 2022 conference (#INCBCN.) Surfing the NASH Tsunami was there, with Jörn Schattenberg serving as event co-chair and Louise Campbell and Roger Green moderating sessions. This week's episode is less a formal recap of the meeting than recollections of key moments and messages from the co-founders and Surfers.
This discussion starts with #INCBCN co-founder Jeff Lazarus and Roger Green what Jeff considered the successes and surprises of the conference. Jeff speaks about the "palpable" energy of the attendees, the number of people who attended virtually and engaged through Q & A and the range of issued addressed at the conference as three strong positives. On a more prosaic note, he also mentions how well the technology worked throughout the meeting. Roger Green suggests that much of the energy came from merging three separate streams of activity -- medical specialists, primary care and patient advocates -- into a single conversation that touched on all three groups' issues. He also suggests that having Marcus Ranney and Jeff to share a digital health vision of the future added additional energy and the prospect of what Roger calls "radical patient empowerment." As co-founder Jörn Schattenberg and then Louise Campbell join the conversation, levity ensues as the four discuss the surprise closing statement from Jeff and Jörn and then a more serious tone as the group discusses the benefits that multidisciplinary conversation brought to all the participants.
Last week, all three #NASHTsunami co-hosts participated in the inaugural Innovations in NAFLD Care (#INCBCN) 2022 conference in Barcelona. Today, co-chair Jeff Lazarus joins Jörn, Louise and Roger in reviewing the conference's high points and key messages.
The meeting itself brought a diverse group of Fatty Liver stakeholders to Barcelona last week to explore NAFLD care from several distinct perspectives. Research Key Opinion leaders discussed not only advances in medicines and diagnostics but also the best ways to utilize what is available today. Patient advocates shared their goals, victories and frustrations working within the current system. Primary care physicians discussed some challenges in incorporating a whole different set of disease screens and thinking into their overloaded practices and ways computing power can help identify patients who need help. Finally, entrepreneur Dr. Marcus Ranney shared a visionary app called Mito that his company, Human Edge, is developing.
This episode is less a recap of the meeting itself than a discussion of its key themes and highlights. The Surfers share their own impressions of the event along with feedback from other attendees. The conversation conveys the enthusiasm and energy present in the room throughout the conference. Along the way, it touches on some of the key concepts presented at the conference.
The final segment of this episode is an abbreviation of a 1:1 interview Roger Green conducted with Marcus Ranney on the specific history of how he came to develop Mito and a broader discussion of the power that decentralized data and analytics can have in improving the health of any patient with a hand-held phone that connects to the internet.
The entire Fatty Liver community benefits from NASH Patient Advocacy and the work of our advocates, but relatively few of us understand what advocates do or how we benefit from their work. Leading German patient advocate Achim Kautz and Global Liver Institute Vice President of Policy and Public Affairs Andrew Scott discuss how they came to Fatty Liver patient advocacy, their priorities and activities that support our community, and the unique challenges of their fascinating work.
This conversation winds up focusing on two key areas to focus future organizing and advocacy. The first is to think locally. Achim and Andrew point out that they can find success working with local and regional governments and then build up from this success to a national discussion. The second is clear, consistent communication between all stakeholders in the Fatty Liver community and between the community and the payers and government forces we need to persuade.
The entire Fatty Liver community benefits from NASH Patient Advocacy and the work of our advocates, but relatively few of us understand what advocates do or how we benefit from their work. Leading German patient advocate Achim Kautz and Global Liver Institute Vice President of Policy and Public Affairs Andrew Scott discuss how they came to Fatty Liver patient advocacy, their priorities and activities that support our community, and the unique challenges of their fascinating work.
This conversation starts with some polite disagreement about whether there is an actual community. At the end of Conversation 23.3, Achim suggested that there is no clear community because of the lack of Fatty Liver focus in specialties and patient groups addressing other metabolic diseases like diabetes, obesity and heart disease. Andrew Scott discusses the work of the Global Liver Institute NASH Council, which focuses on bringing these exact communities into the discussion, at least within the US. The rest of the conversation focuses on using an understanding of metabolic parameters to know which patients should see primary care vs. hepatologists vs. other specialists. It ends with Roger Green asking whether and how politicians, who want solutions that happen quickly and have hard metrics, can get behind this broad an effort.
The entire Fatty Liver community benefits from NASH Patient Advocacy and the work of our advocates, but relatively few of us understand what advocates do or how we benefit from their work. Leading German patient advocate Achim Kautz and Global Liver Institute Vice President of Policy and Public Affairs Andrew Scott discuss how they came to Fatty Liver patient advocacy, their priorities and activities that support our community, and the unique challenges of their fascinating work.
This episode starts with Roger Green inviting Achim and Andrew to discuss a specific success they have had in order to help listeners understand the nitty-gritty details of how their jobs work. After Achim shares a story about bringing patients with multiple metabolic diseases together for advocacy. Before Andrew can answer, Jörn Schattenberg invites Louise Campbell to comment on the disease and target population. She notes the breadth of the Fatty Liver community, from early-stage asymptomatic patients who have never been told they have disease along the spectrum to patients with advanced fibrosis and cirrhosis. Andrew and Achim acknowledge the breadth of patients in the Fatty Liver disease community and describe the process as a delicate balancing act given that the largest number of patients with unhealthy livers have early-stage disease they do not acknowledge or even know about, while the patients with late-stage disease are the ones who seek help most aggressively.
The entire Fatty Liver community benefits from NASH Patient Advocacy and the work of our advocates, but relatively few of us understand what advocates do or how we benefit from their work. Leading German patient advocate Achim Kautz and Global Liver Institute Vice President of Policy and Public Affairs Andrew Scott discuss how they came to Fatty Liver patient advocacy, their priorities and activities that support our community, and the unique challenges of their fascinating work.
This discussion starts with Jörn Schattenberg discussing his first experience in talking with a government official about Liver Health, in the process creating a new Public Sector advocate. Andrew follows this thought by discussing the dual importance of educating public officials and ensuring that the voice of the patient is heard in all public channels and conversations. In response to a question from Roger Green, Andrew and Achim discuss the craft of lobbying public officials. Each paints a clear picture of how many people are seeking the attention and approval of public officials. The conversation ends with Andrew discussing the importance of individual patients' stories in painting a picture for public officials and, specifically, the success that the Global Liver Institute has had in pairing clinicians and patients to bring the Fatty Liver story to elected officials.
The entire Fatty Liver community benefits from NASH Patient Advocacy and the work of our advocates, but relatively few of us understand what advocates do or how we benefit from their work. Leading German patient advocate Achim Kautz and Global Liver Institute Vice President of Policy and Public Affairs Andrew Scott discuss how they came to Fatty Liver patient advocacy, their priorities and activities that support our community, and the unique challenges of their fascinating work.
This conversation introduces you to patient advocates Achim Kautz and Andrew Scott and reveals the vastly different backgrounds they bring to their roles. (Side note: Achim’s “things you wouldn’t know if he didn’t tell you”) is one of our two favorites so far this year.) The differences in their backgrounds are significant, but far more striking is their common passion for elevating Fatty Liver disease priorities in the minds of the government figures with whom they advocate for our community.
The entire Fatty Liver community benefits from NASH Patient Advocates and the work of our advocates, but relatively few of us understand what advocates do or how we benefit from their work. Leading German patient advocate Achim Kautz and Global Liver Institute Vice President of Policy and Public Affairs Andrew Scott discuss how they came to Fatty Liver patient advocacy, their priorities and activities that support our community, and the unique challenges of their fascinating work. Jorn Schattenberg, Louise Campbell and Roger Green, bring their own experiences talking and working with government to a far-reaching conversation that reflects all the complexities that people like Andrew and Achim manage daily.
The episode starts with Achim Kautz discussing his background, including his path from his first career (you'll have to listen to find out) to general liver advocacy to Fatty Liver advocacy. after groundbreakers, the focused conversation starts with Achim and Andrew discussing their backgrounds, motivations and mission. Jorn Schattenberg joins the conversation to discuss his experiences in speaking with politicians about liver health and the impact conversations can have. Andrew follows this story up by describing his focus on getting patients "a seat at the table" when Fatty Liver issues are discussed, debated and decided upon. The discussion shifts to focus on the similarities and differences working in the US and German systems (hint: more similar than different), including compelling comments from Achim and Andrew about how to message to elected officials (very quickly, and with the goal of piquing their interest.)
The rest of the discussion focuses on the complexities and dualities of the patient advocacy task: advocating for a disease with long-term consequences to an audience that thinks in one-year or one election cycle chunks; supporting both the later stage patients (HCC and cirrhosis) and earlier stage (metabolic and CVD-affected) patients, and building cross-communication between stakeholders (and, in the case of providers, different specialties) in a world that organizes around siloes. On a couple of issues, our conversation presents different perspectives. One example: Achim and Louise feel there is no community due to siloing of providers and specialties; Andrew noted that Global Liver Institute's NASH Council focuses on these kinds of collaborations.
This conversation is fueled by intellect, passion and occasional humor and provides a broad perspective on a function that brings tremendous value to our industry.
The 5th Global NASH Congress will take place in London (in person only) on May 27 and 28. Louise Campbell and scientist/entrepreneur Rachel Zayas, who will cover the Congress for NASH Tsunami, join Ian Rowe and regulars Jörn Schattenberg and Roger Green to discuss some key papers and issues covered there. This episode focuses on a range of topics: the importance of weight loss, the challenges of histology and how to overcome them in drug development, and what panelists hope to take away from this meeting.
The 5th Global NASH Congress will take place in London (in person only) on May 27 and 28. Louise Campbell and scientist/entrepreneur Rachel Zayas, who will cover the Congress for NASH Tsunami, join Ian Rowe and regulars Jörn Schattenberg and Roger Green to discuss some key papers and issues covered there. This conversation starts with Ian Rowe and Jörn Schattenberg sharing their perspectives on how much of the emerging genetics and omics of Fatty Liver disease clinicians need to understand. This transitions into a discussion of the drug development presentations in the meeting and what we stand to learn from these.
The 5th Global NASH Congress will take place in London (in person only) on May 27 and 28. Louise Campbell and scientist/entrepreneur Rachel Zayas, who will cover the Congress for NASH Tsunami, join Ian Rowe and regulars Jörn Schattenberg and Roger Green to discuss some key papers and issues covered there. This conversation starts with comments from Jörn Schattenberg and Ian Rowe that focus the group on pre-clinical drug development issues. The group pays particular attention to considering the implications of using precision-cut liver slides and advanced proteomic analytical tools to answer specific questions about how development drugs (monotherapy and combination) will perform in the liver. Rachel Zayas comments on the importance of analyzing cells using a broader, more integrative design rather than simply focusing on the transcriptome and RNA sequencing. The conversation ends with answers to a question posed by Roger Green about how much the typical clinician or leading researchers need to understand about omics.
The 5th Global NASH Congress will take place in London (in person only) on May 27 and 28. Louise Campbell and scientist/entrepreneur Rachel Zayas, who will cover the Congress for NASH Tsunami, join Ian Rowe and regulars Jörn Schattenberg and Roger Green to discuss some key papers and issues covered there. This episode focuses on issues surrounding gut microbiome, its relationship to Fatty Liver Disease and other issues related to nutrition and weight loss.
The 5th Global NASH Congress will take place in London on May 26-27. Surfing the NASH Tsunami is serving as a Media Partner for the event. Professor Ian Rowe and scientist/entrepreneur Rachel Zayas join Jörn Schattenberg, Louise Campbell and Roger Green to review some key presentations and discuss what attendees are likely to learn from the Congress.
The preliminary agenda for the Congress highlights five significant areas of focus: recent updates in NASH pathogenesis; preclinical & translational strategy and new targets for treatment of NASH/fibrosis; non-invasive biomarkers and diagnostic tools; clinical development & clinical trial data and regulatory updates.
The group examines conference presentations on these topics in the order presented here. Rachel Zayas kicks off the conversation by discussing her general excitement at hearing updates about gut microbiome and associations with disease. Rachel notes that the microbiome is sometimes referred to as the "second human genome." She goes on to note that the microbiome might even have a greater impact than the genome, given that "for every one cell of human cells that we have in the body, there are 10 cells of genomes." Jörn Schattenberg notes that Madrigal has explored some of this information in the MAESTRO trials and hopes it may come up in this meeting. Roger Green asks whether there might be a link between food insufficiency/scarcity and gut microbiome, given that so many subpopulations with PNPLA3 dysfunctions live with food insufficiency.
As the conversation moves on, Jörn highlights the paper from Ayse Okesli Armlovich to raise the topic of using human precision-cut liver slices and 3-dimensional cell cultures to study drug combinations and improve the understanding of cellular interactions. This led to a conversation of the unique value of human ex vivo slides in evaluating how different medicines might work.
The entire conversation went like this, interspersing comments about conference presentations with broader discussion placing this in the context of other episodes and clinical trends and papers.
Unfortunately, 5th Global NASH Congress will only be available in person in London May 26-27. Louise Campbell and Rachel Zayas will be attending the conference. They will share what they hear and learn with Roger Green and Jörn Schattenberg on a later episode.
This conversation includes part of a more extended discussion that Donna Cryer had with Louise Campbell and Roger Green when she stopped by the virtual SurfingNASH.com studios to discuss her recent work.
It begins with a discussion between Donna Cryer and Louise Campbell, in which Louise discusses the processes and approaches she uses to educate patients. At the same time, she notes that FibroScan, which is key to her approach, is accessible to only one in four residents of the UK. Louise and Donna shift the discussion slightly to discuss the importance of weight loss and how liver tests can support patients in the early stages of significant NASH-related weight loss by showing how even a small weight loss can have an impact on liver health metrics.
At this point, Roger Green attempts to link this conversation stream to the last stage of Louise's and his conversation the day before with Naim Alkhouri in terms of the value that AI and digital therapeutic applications can bring to Fatty Liver disease. Donna announces her fourth piece of news: that she will be speaking next week at the University of California Health System on the subject of health data and the public good. Donna goes on to say, "as much as my heart is in hepatology, I still love to be connected to this tech space, the digital health space, the air space. I think it's important to the future of health and and and and all of us." This leads Roger to observe that the liver may need digital health and AI more than any other organ system, which leads the group to discuss why digital health is so critical for the progress of treating liver health and the importance of tech literacy in elements of the population who are not very tech literate. The conversation ends with this issue.
This conversation includes part of a more extended discussion that Donna Cryer had with Louise Campbell and Roger Green when she stopped by the virtual SurfingNASH.com studios to discuss her recent work.
Donna starts her conversation by saying that she is bringing three pieces of news with her. The first: with support from Novo Nordisk, the National Committee for Quality Assurance has released a white paper titled, "A Rallying Cry: Improving Coordinated Care for People with Nonalcoholic Steatohepatitis." The second: the American Heart Association has released a paper discussing the link between NASH and heart disease. The third is the initiation of GLI's "Liver Health is Public Health" campaign.
This episode focuses on all three of these developments, along with the Barcelona conference next month and the reality that socially underserved elements of the population have suffered more during the pandemic than those who are better off economically. The conversation moves too fast and with too many digressions to capture accurately, but it is a great, brief listen.
This conversation includes part of a more extended discussion that Naim Alkhouri had with Louise Campbell and Roger Green when he stopped by the virtual SurfingNASH.com studios to discuss his recent work.
This conversation winds up focusing on digital health and future therapies, but it starts down a funny path on the way there. Louise Campbell returns to the question of CAP scores to note that when she sees someone with a CAP of 2.48 or slightly higher, she can use that score to motivate patients to change their regimens. This comment leads to agreement between Louise and Naim about using the low CAP score to set a cutoff for the level at which providers should advocate aggressively for lifestyle changes and the higher CAP for medication. Louise suggests that we might see fewer patients requiring medication with a strong enough push for patients to improve lifestyles at the lower cutoffs.
The rest of the conversation stems from Naim's report about two other sets of research he is working on, one with the behavioral diet app Noom and the other a series of studies on digital therapeutics. We would have to replicate the transcript to do a summary justice. Suffice it to say that the combination of digital therapeutics, NITs and AI can point the way to a medical future far more powerful and individualized than anything we see today.
This conversation includes part of a longer discussion that Naim Alkhouri had with Louise Campbell and Roger Green when he stopped by the virtual SurfingNASH.com studios to discuss his recent work.
Naim dives right into the conversation by mentioning that he has had two papers published within the last week or two. One is from the EDICT Trial, a multi-year evaluation of Type 2 Diabetes patients where half are randomly assigned a course of "conventional" step therapy, and the others are assigned an immediate course of a more up-to-date combination therapy. The conventional therapy includes metformin, followed by a sulfonylurea and eventually insulin. The more up-to-date therapy also includes an initial therapy including metformin along with pioglitazone (which has known effects on diabetes and NASH) and exenatide, an anti-obesity medication. After six years, 69% of the convention therapy group exhibited moderate-to-severe steatosis vs. 31% of the combination therapy group. Further, 26% of the conventional therapy group exhibited F3 or F4 fibrosis vs. 7% of the initial combination therapy group. The other paper involved an analysis of the NHANES database. Using a CAP score cutoff of 3.02, the analysis estimated NAFLD prevalence of 25% and F2 or higher fibrosis of 4.4%. Among Type 2 diabetes patients, the corresponding numbers were 54% and 18%. Naim talked about additional work this study team will do in analyzing the database.
Louise Campbell asks whether the group considered CAP scores of 2.48. 2.60 and 2.83, which are used in some of the meta-analyses. Naim responds that the lowest CAP (2.48) would double the NAFLD estimate to something more like 50% and felt too low a CAP. We come back to this issue in Conversation 21.3.
I close this conversation with the comment that these studies collectively suggest that regardless of whether we find NAFLD or NASH in a T2D patient, we should treat them all as if it is or could be present. Naim agrees, saying that these studies tell him that as a society, we should take Type 2 Diabetes far more seriously and should pressure the medical societies to do the same.
This conversation on NAFLD Care Delivery and NASH practices comes from Episode 20, our introductory conversation with newly designated full-time co-host Jörn Schattenberg. Most of the conversation focused on Jörn's background and research interests, but this section explores ways we can provide better diagnosis, coaching and care for Fatty Liver patients in Germany, the UK and the US.
The conversation stems from an observation Louise makes about how much she appreciates Jörn's focus on integrating primary care into screening and diagnosis. Jörn picks up on this to mention his work with LiverScreen, an EU-funded consortium that screens for Fatty Liver in primary care offices. This has brought him in contact with a significant number of primary care physicians and opened discussions about primary care's role in NAFLD and NASH. Jörn notes how the phenomenon Stephen Harrison has described as "greet 'em and street 'em" leaves primary care physicians short of the time to screen and support patients.
Roger Green asks if the improvising liquid biopsies will help address this problem, which leads Jörn to note that in general, German physicians do not draw blood, which makes liquid biopsies less valuable. This will be particularly true if the blood test is the one shot at diagnosis and the test is FIB-4 or something else with low cost but also low overall predictive ability.
Roger asks about the role of AI in this process, which leads Jörn and, after him, Louise to discuss the value of AI in risk identification, although not diagnosis. This brings the discussion back to the question of pathways, testing and the idea that in the German system, physicians have the latitude to ignore an abnormal liver test and many do so...all of which highlights the importance of physician education, which, as Jörn notes, is a focus of NASH Tsunami and becoming increasing important to the new company, SurfingNASH.com.
Arizona Liver Health Institute V.P. of Academic Affairs and Fatty Liver Program Director Naim Alkhouri and Global Liver Institute Founder and CEO Donna Cryer join Louise Campbell and Roger Green to discuss their recent projects and accomplishments. Each of them brings newsworthy stories that lead to thoughtful, stimulating conversations about a range of issues.
Naim Alkhouri's news includes two recent academic publications and some exciting, innovative new projects. One of his publications, the EDICT trial, contrasted two sets of T2D patients that were treated with different regimens. One set was treated with a "classic" regimen of metformin, a sulfonylurea and insulin -- agents that are liver-neutral or problematic. The other set was treated with a more friendly regimen of pioglitazone, a GLP-1 and metformin. Not surprisingly, when patients in the two groups were evaluated, the differences were dramatic. The other paper was a collaboration with the Pfizer NASH team, looking at 10,000 NHANES patients who were evaluated using FibroScan to estimate the proportions of NAFLD and NASH in the population. The numbers here were consistent with public health estimates. One interesting point: the CAP threshold the researchers used in this paper was far different from what Louise uses when evaluating patients with Tawazun Health. The difference? Louise chooses lower levels in the belief that lower levels will motivate more patients towards self-care, while Naim's higher levels reflect the score at which physicians are likely to prescribe medications. This led to a conversation on the value of this two-metric approach: one level for self-care and a higher one for medication. As Roger notes, this aligns with the concept of "prehypertension" that has him taking steps to reduce his blood pressure slightly without the aid of medication. Naim goes on to discuss two novel sets of studies he is conducting, one with the diet app Noom and the other with a range of digital therapeutics companies.
Donna Cryer begins by announcing she has three pieces of news to report: a recently released paper supported by Novo Nordisk and developed with a group convened by the National Committee for Quality Assurance, titled "A Rallying Cry: Improving Coordinated Care for People with Nonalcoholic Steatohepatitis," a scientific statement from the American Heart Association on the connection between NASH and cardiovascular disease, and the formal launch of GLI's "Liver Health is Public Health" campaign. The NCQA paper and entire idea of liver health as public health launch spirited conversation with emphatic agreement among the three participants. When Roger shares some thoughts from Naim's conversation about the potential for digital heath apps to become personalized and tailored over time, it leads Donna to a fourth announcement about a talk she is giving next week at the University of California Health System on the use of data for the public good. As with Naim, the conversation turns to the use of digital health in its many forms to improve liver care.
Combined with the Episode 20 conversation with the three permanent Surfers, this episode connects the many streams of Fatty Liver research into a single package that is part pharmacotherapy, part better diagnostics, part digital health and part public policy.
SurfingNASH.com has produced this special, single-interview episode to give listeners a chance to learn about Jörn Schattenberg in a different way as he becomes the permanent Key Opinion Leader on Surfing the NASH Tsunami.
Surfing the NASH Tsunami's "Seasons" start with the calendar year, but our first episode posted on April 15, 2020. As we begin our third year, we wanted to give listeners a chance to get to know Jörn Schattenberg a bit differently than you would just from listening to episodes. Jörn discusses how he decided to become a hepatologist, why Stephen Harrison's phrase "Greet 'em and Street 'em" has such resonance, the basic science work his laboratory in Maïnz does, and where he sees the podcast fitting into the future of Fatty Liver disease. Louise Campbell and Roger Green ask questions and share viewpoints in this fast-moving conversation.
This conversation starts with Stephen Harrison discussing the scope of current NITs in the context of what NAIL-NIT needs to achieve. "We don't need to reinvent the wheel, " he says, "only to make it run smoother." After Naim Alkhouri and Mazen Noureddin discuss the Phase I facilities they are building for future research, the group closes the conversation by focusing on the medical, commercial, financial and patient-centric imperatives that make it so imperative to develop appropriate NIT-based solutions for drug development, diagnosisis and patient management within the next five years.
This week marks the 2nd anniversary of Surfing the NASH Tsunami! Thank you for being part of the process that has brought us this far: 126 episodes and 335 separate podcast postings and over 58,000 downloads by individuals in over 105 different countries! We promise you this: the best of NASH Tsunami lies ahead of us.
This conversation starts with discussing how challenging it was to develop initial FDA test criteria for evaluating NASH drugs. Many years later, he notes, we have learned how flawed these criteria were, several in ways we cannot fix, but we need to do better. He relates this to what the British author Rupert Sheldrake describes as "morphic resonance" or mysterious telepathy type interconnections between organisms and collective memories within species. Once thing leading hepatologists have learned is that you can look at a liver or liver data and get a clear since you are looking at NASH, but it is harder to generate and vet consistently clear data on this point. He points to the REGENERATE trial as a place where specific data analysis did not reflect the gestalt impression and says, “that is what we need to get beyond.”
Louise Campbell interjects a very different kind of question, asking whether the NAL-NIT analyses can include questions that patients answer on initial screening in pursuit of AI-driven analyses of these questions to screen patients into or out of further tests..an idea that draws an immediate, enthusiastic response from Naim Alkhouri. In the end, the discussion turns light-hearted and focuses on how many papers the panelists will have to produce in the first year of the program.
This week marks the 2nd anniversary of Surfing the NASH Tsunami! Thank you for being part of the process that has brought us this far: 126 episodes and 335 separate podcast postings and over 58,000 downloads by individuals in over 105 different countries! We promise you this: the best of NASH Tsunami lies ahead of us.
This conversation starts with Naim Alkhouri and Jörn Schattenberg defining the wealth of data resources and hypotheses they are bringing to their roles as co-leads of retrospective analysis for NAIL-NIT. Mazen Noureddin then asks each of them to describe his "passionate first project." This leads Naim to discuss drug evaluation principles he finds so counterproductive that they fit into Nassim Taleb's definition of "IYI" ("Intellectual Yet Idiot"). As the discussion ends, Roger Green ties this issue to the analytical fallacy of quantifying a soft qualitative measure for drug evaluation purposes and Mazen points out that we will need to expand patient evaluation to NIT-only rules in order to recruit enough patients for all the drug trials on the horizon.
This week marks the 2nd anniversary of Surfing the NASH Tsunami! Thank you for being part of the process that has brought us this far: 126 episodes and 335 separate podcast postings and over 58,000 downloads by individuals in over 105 different countries! We promise you this: the best of NASH Tsunami lies ahead of us.
In this brief conversation, Stephen Harrison discusses the exciting goal and ambitious research plan for NAIL-NIT, after which Mazen Noureddin describes the patient-focused issues and conference conversations that motivated Stephen and Mazen to form and recruit members for this consortium. It is a short but rich listen that will help you understand exactly what NAIL-NIT is driving to accomplish.
This week marks the 2nd anniversary of Surfing the NASH Tsunami! Thank you for being part of the process that has brought us this far: 126 episodes and 335 separate podcast postings and over 58,000 downloads by individuals in over 105 different countries! We promise you this: the best of NASH Tsunami lies ahead of us.
This week marks the 2nd anniversary for Surfing the NASH Tsunami! This conversation celebrates our anniversary and brings news about the formation of a new company dedicated to using podcasts and related media to put big dent in Fatty Liver disease and changing roles for co-founder Stephen Harrison and "fifth Beatle" Jörn Schattenberg.
Before you listen, you might want to join us in the "Stephen Harrison Drinking Game." Get a cup or glass of coffee (hot or iced, as you prefer), feel free to add a non-dairy milk and low-glycemic index sweetener if you need to. Then write down a "Harrisonism" (a distinctive phrase commonly associated with Stephen). Then listen to this conversation to see whether any of our panelists (Stephen, Jörn, Louise Campbell, Mazen Noureddin, Naim Alkhouri and Roger Green) select the same phrase you did.
This 2nd Anniversary episode focuses on what the retrospective analysis from the NAIL-NIT consortium can achieve in terms of driving the shift beyond the biopsy in NASH diagnostics while simultaneously celebrating Stephen Harrison's contribution to the podcast while announcing that Jörn Schattenberg will become our weekly Key Opinion Leader (other commitments will force Stephen Harrison miss roughly half the episodes).
The first part of the discussion focuses on Stephen's role in the podcast, culminating in what SurfingNASH's audio engineer, MiC Wilson, has dubbed "The Stephen Harrison Drinking Game." (Listen to learn about it.)
Stephen begins discussion of NAIL-NIT by describing what triggered this effort - a chance to "break down stovepipes" (Harrisonism) to create a multi-study data set that can address some of the biggest issues we face today around NITs. "We want to find the right tests for the right situation at the right time to answer the right question" whether that's diagnosis, monitoring for therapeutic efficacy or prognosis."
Stephen then describes a two-step process: (i) Analysis of retrospective data from completed and existing clinical trials, which should provide guidance, followed by (ii) a prospective study that can "nail" the right NIT for each situation within the next 5-6 years.
Mazen discusses the patient perspective: what happens for the patient (and physician) who clearly has NASH (maybe even F3) but cannot get into a trial because the biopsy does not reveal presence of ballooning? Over time, casual discussions about this issue with Stephen led them to drive the NAIL-NIT initiative. Mazen goes on to note the valuable work that LITMUS, NIMBLE and the Goldmine project at UCSD have done, but feels that this is the time - and NAIL-NIT is the project - to pull all this together into a focused, eventually conclusive effort.
After Naim and Jörn discuss their motivation to participate, Mazen shifts the tone of the conversation by asking each of them to describe his "passionate first project." Naim's answer focuses on thresholds that correspond to histological responses for the different NITs. Jörn focuses on questions of effect size, particularly related to varying placebo responses across different trials.
Naim then goes on to quote Nassim Taleb, author of the recent book, "Skin in the Game," on a concept he describes as "IYI", "intellectual yet idiot". Naim provides two examples of IYI in NASH trials. Example 1: an F3 patient cannot be enrolled in a trial due to lack of balloon hepatocytes. As Naim notes, F3 is "aggressive disease," so, he asks, "what else do you need to know?" Example 2: a 0 score on ballooning is required to describe a patient's NASH as having reached resolution.
Mazen notes that in a future with 10-15 Phase 3 trials, we will never generate the requisite sample sizes if trials are tethered to biopsy and ballooning. Stephen cites the English author Rupert Sheldrake on the concept of "morphic resonance." Here, it means that you can know something is NASH even if specific metrics do not prove it.
After Jörn discusses the project's ability to shape the prospective trial, Louise asks whether the group plans to analyze presenting symptoms. She points out that a goal of research should be to develop a questionnaire a primary care physician can administer to the patient that will point those at higher risk toward additional evaluation.
From there, the discussion focuses on other implications of the trial on drug development and patient diagnosis and care. There is not enough room to describe all of it. Listen on to learn why a 5-year timeline to get the answer both makes sense and might be imperative.
Make sure to allow the energy and "get it done" (another Harrisonism) tone of the conversation to sink in...
This week's episode and conversations preview the inaugural Innovations in NAFLD Care Workshop, premiering in Barcelona on May 6 and 7. Surfing the NASH Tsunami is a Media Partner for this conference. We will be conducting and posting interviews from the conference, co-host Roger Green is moderating a panel there, and Surfing NASH will present a follow-up episode on Wednesday, May 11.
This conversation previews Sessions 4, 5 and 6, which comprise the bulk of the Day Two Agenda. The overall theme of the day is that NASH treatment is integrated and multifactorial. The day starts with Jeff Lazarus discussing Comprehensive Care Models for NASH, the path there and desired endpoints. The rest of Session 4 focuses on two forms of technical support: integrating non-invasive tests for NAFLD into clinical practices outside the liver space and looking at the power of apps to transform the weight management process. Session 5 focuses on pharmacotherapy, including use of current pharmacotherapy in weight loss and diabetes and some of the future agents that will come into use over the next few years. Finally, Session 6, which Roger Green will moderate, pulls together a diverse set of panelists to consider the NAFLD/NASH Roadmap in the context of social media and digital transformations. Listening to this conversation provides a clear sense of how broad the scope of Day Two issues will be.
In the interest of time, this summary does not list the names of the speakers giving each talk. This is an absolutely first-class global faculty. If you are curious, go to the meeting program to learn who these exceptional speakers are.
This week's episode and conversations preview the inaugural Innovations in NAFLD Care Workshop, premiering in Barcelona on May 6 and 7. Surfing the NASH Tsunami is a Media Partner for this conference. We will be conducting and posting interviews from the conference, co-host Roger Green is moderating a panel there, and Surfing NASH will present a follow-up episode on Wednesday, May 11.
This conversation focuses largely on Session 3 of the Innovations in NAFLD Care 2022 Workshop and the Patient Organizing Session that starts Day Two.
Session 3 focuses on the role that different types of health professionals will need to play for a successful attack on the coming NASH pandemic. Specifically, it looks at differences between what primary care physicians, nutritionists and bariatricians can achieve. The first two talks are expected to touch on structural issues and well as individual patient care. The bariatrician talk will present study data and devote significant attention to practical uses of endoscopy and non-invasive tests to track and demonstrate progress.
Before the discussion shifts to Day Two, Roger Green asks the co-chairs what they hope listeners will take away from Day One. Answers focus on two related issues: the scale of the NASH pandemic and how much impact health professionals can have for individual patients.
The rest of this conversation revolves around the importance of patient organizations both in motivating and educating individual patients and in driving broader social change around liver health issues.
One of the gaps in diagnosis and treatment is the question that different specialists need guidance to appreciate the roles they can play in the process. This session discusses the role that primary care physicians, nutritionists and bariatricians each can play on diagnosing and treating NAFLD and NASH patients.
The primary care discussion focuses on what is feasible for a primary care physician in a time-constrained environment to achieve in terms of NASH. The nutritionist point of view looks at both individual and structural issues. The individual issue is exactly what it sounds like -- wayss to support individual patients during liver workups. The structural issues address food insufficiency and poor dietary choices. The bariatric discussion will focus not only on population studies, but on practical use of different interventions and NITs to be certain that these interventions are having desired effect on the bariatric patient's liver.
In the interest of time, this summary does not list the names of the speakers giving each talk. This is an absolutely first-class global faculty. If you are curious, go to the meeting program to learn who these exceptional speakers are.
This week's episode and conversations preview the inaugural Innovations in NAFLD Care Workshop, premiering in Barcelona on May 6 and 7. Surfing the NASH Tsunami is a Media Partner for this conference. We will be conducting and posting interviews from the conference, co-host Roger Green is moderating a panel there, and Surfing NASH will present a follow-up episode on Wednesday, May 11.
This conversation focuses on the first two sessions of the Innovations in NAFLD Care 2022 workshop. Jeff Lazarus defines Session 1 as "Epidemiology for Action." His underlying point: NAFLD is part of the metabolic family of diseases, but many of the specialties that treat other diseases in the metabolic famliy are not trained even to look for liver disease. As Jeff notes pointedly, "when we review the cardiology guidelines and we don't see liver mentioned except for the word to deLIVER on better cardiological outcomes, you know we have a problem." The epidemiologic numbers are staggering in their own right (25% of adult population with NAFLD, 25% of these with NASH; 25% of these with cirrhosis), but the point here is that many different specialists treat these patients without ever being taught or encouraged by guidelines to screen for liver disease. This session starts a presentation asking, "Is NAFLD/NASH a Public Health Challenge in 2022?", followed by presentations on cardiovascular links to NAFLD and NASH and the "Fatal Triple" of Obesity, Type 2 Diabetes and NAFLD/NASH. Jörn Schattenberg follows Jeff by presenting the second session, which focuses on the role screening must play and effective strategies and tactics. The first presentation in this session focuses on a clinical care pathway for screening. The second focuses on a UK-based program that computes test results for general practitioners, thereby simplifying their task of identifying patients at risk. The third goes back to the beginning of the clinical care pathway to discuss "How and Why to Identify NAFLD in Primary Care?"
In the interest of time, this summary does not list the names of the speakers giving each talk. This is an absolutely first-class global faculty. If you are curious, go to the meeting program to learn who these exceptional speakers are.
This week's episode and conversations preview the inaugural Innovations in NAFLD Care Workshop, premiering in Barcelona on May 6 and 7. Surfing the NASH Tsunami is a Media Partner for this conference. We will be conducting and posting interviews from the workshop, co-host Roger Green is moderating a panel there, and Surfing NASH will present a follow-up episode on Wednesday, May 11.
This conversation between co-host Roger Green and the co-chairs and co-founders of the Innovations in NAFLD Care 2022 workshop, Jeff Lazarus and Jörn Schattenberg, focuses on the factors that drew each man towards these issues and to create this kind of event. For Jeff Lazarus, this is the third wave on what he describes as his own liver Tsunami, starting with his work on HIV, moving to Hepatitis C because many of the same people living with HIV were also living with Hep C and then, once he realized that prevalence of cirrhosis and hepatocellular carcinoma (HCC) was growing despite these effort, to look at NASH as the looming source of a pandemic of severe liver disease. Jeff notes that whereas HIV and Hepatitis C were well defined diseases when he became involved and there were effective therapies for both these diseases NASH is quite different: a less-than-clearly defined disease with no discrete new agents in market. Jörn Schattenberg came from quite a different perspective. Jörn started as a clinical and academic hepatologist, treating patients and working in drug and diagnostic development. His first exposure to public health came while working on a cost effectiveness paper with Jeff. As he became increasingly involved with public health and policy, he learned how complex it is to build a consensus to organize effective treatment for NASH patients.
Jeff's and Jörn's stories comprise the bulk of this conversation. The only other thought comes from Roger Green, who comments that one thing the three conditions have in common is the inappropriate stigma attached to patients with each.
Conference founders and directors Jeffrey Lazarus and Jörn Schattenberg join Roger Green to preview the inaugural Innovations in NAFLD Care 2022 conference, scheduled for May 6 and 7 In Barcelona and on-line. Jeff Lazarus describes this conference as "looking at Fatty Liver disease from a Public Health perspective." As Jörn Schattenberg expressed, this has been a process over "incredibly productive years" of "just pulling people together and getting this into a movement that I think finally leads up to the conference we're having now."
This process has already produced half a dozen or more papers on issues relating to NAFLD, cost and public health, overseen a process by which over 200 countries participated in a three-stage Delphi process, created a consensus statement, held a workshop in January and, now, sponsored this inaugural conference.
After Jeff and Jörn finish discussing the motivations to create this process and how they feel about activities to date, the discussion turns to a session-by-session review of the Conference. Jeff Lazarus leads the review of the first session, which he describes as "epidemiology for action," an effort to motivate a broader set of healthcare providers, including endocrinologists, cardiologists, primary care physicians, nutritionists, allied health professionals, to think about the liver of each patient they treat when working them up. As Jörn points out, the title of this session includes the provocative phrase "Measuring a Silent Condition," which was intended by its authors to convey the scale and hidden nature of the challenge.
Discussion shifts to the next two sessions. Session Two focuses on screening and Session Three focuses on treating NAFLD patients in different care settings. While the topics may be different, the sensibilities behind the two sessions are similar: we need to bring a broader swath of health professionals to this effort and to provide them with tools that make it as simple as possible for them to play a role.
Discussion of the Day Two agenda starts by discussing the importance of patient organizations and advocates in driving this process forward, then shift to the three sessions that will take most of the day. The title of Session Four conveys focus on the multidisciplinary management of care; the talks focus on comprehensive care pathways, the best way(s) to integrate non-invasive liver tests outside the clinical trial setting and, finally, the ability of digital technologies and information to create apps and programs that produce effective weight management results. The Title of Session Five conveys focus on the future of pharmacotherapy, but two of the talks discuss obesity and diabetes medications that may be available today. Finally, Session Six constitutes a far-ranging group discussion covering all the elements of the meeting so far, wrapped around the broad question of the ways that social media and digital transformation can help inform care pathways and comprehensive care plans for NAFLD patients.
This description lists the sessions and summarizes their focus because an effort to describe in detail will require more characters and writing space than Buzzsprout provides. Suffice it to say that this conference is the most complete manifestation to date of the unique perspective and Jeff and Jörn have shared on earlier episodes of this podcast.
Professors Scott Friedman and Neil Henderson join the Surfers (including the returning Stephen Harrison) to discuss some truly exciting advances in the basic science and technology of defining, diagnosing and treating NAFLD and NASH. This conversation focuses largely on questions of how hepatic cells regenerate and what more we can learn about this phenomenon over time as technology improves.
Unlike the first three conversations, whose pace ranged from "rapid-fire" to "hold on, we're racing", this conversation goes at a slightly slower pace. It starts with Stephen signing off by discussing how helpful this kind of disucssion is for someone focusing primarily on drug development today and congratulating Scott once more on his recent award.
Louise Campbell asks a cautionary question: what if when we replicate the liver's ability to regenerate tissue, it doesn't stop but generates more tissue than the liver needs, thereby creating hyperplasia? Scott responds by noting that his concern is not hyperplasia in itself, but that the regenerating liver will grow more cancer cells. He describes the need to "walk a tightrope" where we regenerate healthy cells but "do not overexcite them to the point where they turn into a cancer," particularly since some of the same processes inherent in regeneration are also found in cancer cell proliferation. Neil agrees, but also comments on the remarkable plasticity of the liver that you can find a "bad" liver scar, clear the scar and have tissue evolve into functional liver tissue once more. It is conceivable, Neil notes, that we could attain the "Holy Grail" of clearing bad fibrosis and having the liver regenerate itself to normal function.
On the last round of questions, each remaining participant (Stephen having departed) found something truly valuable and/or profoundly interesting in this discussion. Scott describes the general goal as "developing the right treatment for the right cell at the right time in the history of the disease." He goes on to note that these technologies have helped us learn that the right treatment for a cell in earlier stage disease might differ from later stage, and similarly, the right treatments for two cells at any stage in disease might not be the same. Neil agrees on the issue and goes on to note the challenge of getting through the voluminous amounts of data being created "but boy, is it fun!" Jörn looks from the drug development perspective to note that "individualized pathophysiology" may be necessary to learn why a given drug will work in one patient and not another, but that these tools may enable us to analyze at that level. Louise looks toward these techniques as a way to diagnose earlier when disease burden is lower on the patient and therapies are less costly and intensive. Neil raised the hypothetical prospect of complex molecular diagnostics that can answer these questions using non-invasive modalities, which sounds like a dream but, at the end of a recent conversation with imaging colleagues, "doesn't seem like Saturn." Finally, Roger talks about the idea that this information challenges and simultaneously enriches the concept of longitudinal combination therapy. From this conversation, it seems likely that an F2 patient who has regressed from cirrhosis has differences in cellular structure compared to a newly diagnosed patient with F2 disease. These tools will provide the richness to treat each in the most effective way. Scott wrapped up the discussion by citing work suggesting that when the liver regresses and doesn't need active stellate cells to make scar, some die...but others simply inactivate. Using Roger's example, he asks whether F2 therapy after patients regress should focus on inactivated cells or cells that have never activated in the first place, "and we know they are different."
And with that, an exceptionally energizing and intellectually stimulating episode came to an end.
Professors Scott Friedman and Neil Henderson join the Surfers (including the returning Stephen Harrison) to discuss some truly exciting advances in the basic science and technology of defining, diagnosing and treating NAFLD and NASH. This conversation focuses largely on the spatial transcriptomics: its history, what it can tell us today, and how it might improve even further over time. All this places focus on the need for healthy hepatic cells researchers can use with this technology, which may already suggest that cells we once considered "good enough" are not today.
Neil starts this conversation by describing the value of spatial transcriptomics today by using what Scott describes as the "blender analogy" developed by Neil's colleague Prakash Ramachandran. This starts with days where we would "mash up" tissue together and redo RNA analysis (in this metaphor, like blending fruit in a blender into a smoothie and trying to taste for the flavors) to a next stage where you can tell what the individual fruits are to spatial transcriptomics today, which is like looking at a fruit tart in three dimensions, seeing where each piece sits in the fruit and the size and nature of spaces between them. As Neil points out, this allows the technology to barcode the spots so the informatics people can work out individual gene expressions.
Roger asks Neil to walk the audience back through the history of how we came to this place technologically. He starts with the early days of single cell genomics and proceeds through high throughput droplet-based systems to cDNA libraries that enable informaticians to indicate exactly which gene is expressed in which individual cell.
Beyond that, Neil discusses the power of single nuclei sequencing, which provides rich data from frozen tissue and thereby provides greater space for global collaboration and examining tissue that might have been stored for years. In the liver, this has allowed for hepatocyte sequencing, which was not viable previously...and there are more advances yet to come.
At this point, the conversation shifts toward what's current and tangible as Jörn Schattenberg asks how much variability in tissue samples can be attributed to human differences. Neil describes his group as "nicely quite surprised at how congruent some of the data has been."
The rest of this conversation centers mostly on sources of tissue on how "healthy" that tissue actually is. In Edinburgh, Neil notes, much of his tissue comes from distal liver sites in patients with colorectal cancer. The sites may be free from cancer but may have effects from earlier chemotherapy and other systemic challenges. Scott wraps up this conversation with the story of a patient where pathologists captured tissue "far away" from the site of a neuroendocrine tumor. Pathologists believed the tissue was healthy, but single cell sequencing revealed a "hugh neuroendocrine cell population." Such is the value of the new technologies and the challenges they face for researchers to improve other elements of the process.
Professors Scott Friedman and Neil Henderson join the Surfers (including the returning Stephen Harrison) to discuss some truly exciting advances in the basic science and technology of defining, diagnosing and treating NAFLD and NASH. This conversation focuses largely on the implications of potentially exciting future technologies such as the mRNA/CAR-T therapy described in Conversation 17.1 on NASH drug development today.
After the earlier discussion of the potential future mRNA/CAR-T therapy, Scott Friedman turns to Neil Henderson and asks this question: "What cell type and what receptors on those cells do you hone in on or do you do more than one? And how do you use single cell genomics to help you sort through that complex question?"
Neil immediately connects the question and the technology to the need for precision medicine in NASH. He points out that one challenge with NASH is hitting a single target is always challenging, particularly when the target is as "evolutionarily conserved" as fibrosis. To Neil, this suggests that if the mRNA/CAR-T therapy comes to fruition, it will become one element -- an important one, but not the only one -- in what he describes as "multimodal combinatorial therapy" which combines medicines and technology to attack fibrosis, perhaps all at once or possibly in stages.
Stephen Harrison says this information leaves him feeling like he is "very much at the very tip of the archeological dig" into what we know about treating Fatty Liver disease. He points out that one rule in drug development today is "if you get rid of the fat, the liver will take care of itself." Following this logic, he suggests the best place for something like the mRNA/CAR-T approach might be in cirrhotic or pre-cirrhotic patients with the goal of regressing fibrosis sufficiently that other more metabolic drugs might become appropriate and adequate as therapy
Scott points out that 90% of all fatty livers never go on to develop cirrhosis. Given this fact, one key focus of learning must be determine why it is that some livers progress and others do not. This would allow us to develop therapies targeted at the livers that progress and the cellular or genetic factors that lead them to do so. This, Scott points out, leads us back to the question of how we can use single cell technologies to learn the role that each cell type plays at different points in disease progression. This leads to a discussion between Neil, Scott and Stephen about the specific challenges of obtaining the liver tissue necessary for these kinds of assessments.
Professors Scott Friedman and Neil Henderson join the Surfers (including the returning Stephen Harrison) to discuss some truly exciting advances in the basic science and technology of defining, diagnosing and treating NAFLD and NASH. This conversation focuses largely on mRNA/CAR-T anti-fibrotic therapies.
Scott Friedman starts this conversation by reviewing the historical sequence that led to the development of an mRNA vaccine that can create CAR-T cells in mice for the express purposes of attacking fibrotic tissue.
Originally, CAR-T was developed to create cells that kill certain lymphomas. In the original design, white cells were extracted from the patient's body and modified via DNA to include a special type of receptor on the cell. This receptor can target tumor cells and destroy them. Late in the last decade, researchers at Memorial Sloan Kettering in New York and the University of Pennsylvania published work demonstrating that when appropriately modified, CAR-T cells could destroy fibrogenic cells in mouse models, both in the liver (MSK) and the heart (UPenn).
Two challenges with current CAR-T therapy is that cells must be removed from the patient's body to create the CAR-T cells (costly and carrying some risk) and that the original genetic material has been found in some patients' bodies as long as a decade after therapy. A third challenge revolves around the high percentages of patients (12-20%) exhibiting Level 3 or higher Cytokine Response Syndrome (CRS) as an effect of therapy.
The UPenn group addressed the first two of these challenges by adapting mRNA technology (which underlies the Pfizer/BioNTech and Moderna COVID-19 vaccines) to modify white cells in the body to attack fibrogenic cells in the heart, with similar effect to the externally generated cells. This addresses the first challenge because you can take "off the shelf" mRNA proteins and inject them into any patient's body and expect highly consistent results (similar to the COVID-19 vaccine). It addresses the second challenge because mRNA is a protein packet that, after completing its work, dissolves into the body and is excreted.
While there are still many vital questions to be answered (CRS issues and transferability from mouse models to humans, to name two), this technology can provide a uniquely powerful way to regress late-stage NASH fibrosis and cirrhosis.
Before this conversation ends, I raise the point about impact on CRS (no answer at this time) and Jörn Schattenberg asks Neil Henderson which cell type and receptor this therapy should address (and whether there are more than one). This question arises in the next discussion.
Professors Scott Friedman and Neil Henderson join the Surfers (including the returning Stephen Harrison) to discuss some truly exciting advances in advanced NASH omics, including work on mRNA/CAR-T anti-fibrotic therapies.
There is not enough room to capture this entire conversation in a summary. It's a lot, but really eye-opening and exciting. Take the time to listen to the entire episode, even if in bite-sized pieces.
This episode starts with bonhomie and humor as the group congratulates Professor Friedman on being honored with a Lifetime Achievement Award from the faculty at Mt. Sinai, and then listens as Professor Henderson relates one of the most truly unique "one thing you wouldn't know about me if I didn't tell you" in the history of the podcast.
The science portion of the podcast starts with Scott discussing a fantastic series of advances in basic science, wherein researchers have begun to evaluate CAR-T therapy, which was originally developed to treat lymphomas and other blood dyscrasias, to attack the surfaces of fibrogenic cells in the liver (MSK, New York) or, separately, the heart (University of Penn). Today, we create CAR-T cells by taking cells from the diseased patient, re-engineering them and injecting them back into the patient. This approach is associated with high rates of Level 3+ cytokine response syndrome (CRS). It has also been found to leave this engineered CAR-T material in the patient's system for at least a decade after therapy.
Scott goes on to explain how the Epstein lab at Penn integrated the CAR-T strategy with mRNA, the protein behind the Pfizer/BioNTech and Moderna DOVD-19 vaccines, to create a vaccine that can reprogram cells within the body to replicate the CAR-T effect. Scott notes that so far, this has only been reported in mouse models, and that there are many major issues to resolve before we know it will be safe and effective in humans. It is a staggering breakthrough nonetheless.
After a couple of questions, the group turns to Neil, who points out that this kind of finding can help "make precision medicine a reality," in part because it creates the possibility we can target multimodal therapy at the precise location it is needed. Stephen suggests that the ideal place for this kind of therapy might be in a late-stage patient where we can regress fibrosis and, once the liver is better able to function, resort to a more metabolic therapy.
Scott suggests how helpful it would be to develop insight into how different types of cells respond to different medication, which shifts the conversation toward the broader topic of single-cell genomics, and specifically, the growing utility of spatial transcriptomics in these situations. Neil provides a description of the benefits of spatial transcriptomics, and then takes the group back through a history of omic technology.
Jörn Schattenberg asks what these techniques have taught us about variability between patients. Neil discusses the congruence of individual samples. Jörn points out this would mean that we can develop robust therapies targeted at a cell type. Scott suggests that we can use these insights to standardize clinical trials, to target the specific patients with the genetic targets most likely to respond -- a large step on the path to personalized precision therapy.
In response to a question from Louise Campbell about sources for liver tissue, Neil asks for study purposes, "What is a normal human liver?" One of his major sources of tissue are distal liver sites from patients with colorectal cancer. However, even if these are cancer free, thy could be affected by chemotherapy.
As discussion winds down, the group comes to focus on the issue of why and how the liver regenerates. It raises fascinating questions: why does it not seem to "over-regenerate?" Are the regenerated cells different from pre-injury cells, and if so, how?
The conversation was originally recorded on January 27, 2022. It focuses on use of MR Elastography to diagnose, treat and monitor NASH patients in an outpatient setting through two uses of MRE -- the MAST test, which includes MRE, MRI-PDFF and AST and the basic Hepatogram test, which includes MRE and MRI-PDFF, or, as Mazen Noureddin describes it during the conversation, MREFF.
This conversation is too long and detailed for a typical section-by-section synopsis, so this write-up will summarize the major elements. After introductions and icebreakers, Mazen Noureddin starts the conversation by discussing MAST and how he came to develop the test. Fundamentally, Mazen saw this as a way to capitalize on and improve what researchers found while constructing and testing the FAST score. His basic logics was "if FAST can produce valuable results and MREFF produces more granular and consistent results than FibroScan, why don't we evaluate the idea of a test that relies on MREFF?" The resulting study produced several promising outcomes: good NPV, "reasonable PPV," higher Area Under Curve than with FAST and a multiple logistic regression analysis identifying MRE as the most powerful predictive factor, followed by PDFF and only then AST (AST was a powerful factor in similar FAST analysis).
The next stage of the conversation addresses practical short- and long-term issues around MRE use in the community. Scott Reeder discusses the practicality and economics of community MRE testing: a one breath-hold test can produce MRE, PDDD and liver iron concentration (LIC), which leads Mazen to describe the new test as "MREFFLIC." Scott goes on discuss how he came to use MRE in Fatty Liver initially (pediatric NASH), to note that capital enhancements for MRE are low and that insurance reimbursement runs ~$300 test (later, Kay will estimate $170 - $200.) Kay continues to estimate that there are ~1,000 MRE machines in us in the US today.
Stephen Harrison follows Kay, discussing the likelihood that FDA will approve MRE in place of biopsy over time, and going on to discuss why MRE will probably turn out to be superior to biopsy. A major factor: MRE looks at the whole liver (which is a heterogenous organ), while biopsy looks at a slice that might be no greater than 1/700,000th of the liver. Scott notes that imaging studies with MRE are showing treatment effect and hypothesizes this might be the reason why. The conversation wraps up with 10 minutes looking at the practical benefits and challenges us using MRE today and how these might resolve over time.
This conversation is sponsored by Resoundant, a Mayo Clinic company and the developers of Magnetic Resonance Elastography. MRE is widely available with over 2000 locations worldwide, and can be done as a low-cost, rapid exam in just 5 minutes. Together with PDFF, this quantitative exam is called an Hepatogram – a powerful non-invasive alternative to liver biopsy in many cases. For more information, visit www.resoundant.com on the web.
This conversation starts by focusing on issues related to diagnostic testing and what we attempt to detect or prove with each test. It starts with Roger Green noting the challenge of widespread population testing for fast progressors: the easy, inexpensive test for widespread 1st-line population testing is FIB-4, but FIB-4's lack of positive predictive value makes it a poor test for assessing this question, besides which, as Alina Allen notes, FIB-4 will increase with age.
Chris Estes comments that modeling costs of a given approach must not only take into account the actual cost of an intervention (a drug, or surgery), but also the costs of testing, false positives, failed therapies and everything else that is part of patient diagnosis, treatment and monitoring. This leads into a brief detour on expected rates of adherence to pharmacotherapy for different types of medications.
The final portion of the main episode explores how costs are likely to change over time and the value of interventions like a sugar tax of soft-drink cup size restriction. This section includes some specific modeling challenges coupled with a general recognition that prevention is less expensive in the long-run than treatment but more difficult to fund and support in the short run. In the end, the group agrees on the need to keep collecting data and maintain a holistic perspective on NAFLD and NASH in the overall context of metabolic disease. As Chris points out, the economic effects on NASH of an effort to reduce Type 2 Diabetes are likely to be extremely powerful.
This conversation is sponsored by Resoundant, a Mayo Clinic company and the developers of Magnetic Resonance Elastography. MRE is widely available with over 2000 locations worldwide, and can be done as a low-cost, rapid exam in just 5 minutes. Together with PDFF, this quantitative exam is called an Hepatogram – a powerful non-invasive alternative to liver biopsy in many cases. For more information, visit www.resoundant.com on the web.
This conversation explores the impact some suggestions and questions that arose at Liver Connect might have on data modeling. Roger Green starts by mentioning that the Liver Connect panels felt that waist circumference measurement might be a better treatment/diagnostic metric than BMI, since it reflects both fat distribution within the body and region of the world. The group generally agreed that while waist circumference has value in diagnosing and treating individual patients, it's relative scarcity of data and inconsistent administration from one practitioner to another (key question: exactly how consistent in the definition of "waist"?) made it a weaker metric than other obesity measures for data modeling.
From there, Alina Allen raised the issue of increased alcohol use and its impact on obesity (not yet measured, but likely to be a serious trend over time with negative impact on longevity and quality of life). During this conversation, the group also explores the value of regressing fibrosis levels vs. simply halting progression (thought: goals should vary based on patient age, fibrosis level and co-morbidities).
Finally, the conversation turns to the idea of "fast progressors," with Alina and Jörn Schattenberg stating that slow progressors should be the research priority because they are so much more common. Alina suggests that what we call ""fast progressors" might in fact simply be people diagnosed late in the course of disease. As Chris notes, the overall pattern of disease, with its period of dormancy and spontaneous regression, makes this issue a challenge to model. The final comment comes from Roger, who points out that patients during fast progression or rapid decline are the most attractive patient targets economically, since per capita spend will be higher and will continue to increase in later stages of disease. However, he adds, we will need to track patients far more frequently than we do now to confirm or disprove any of these hypotheses about the nature of fast-progressing disease and the proportion of patients who are actual fast progressors.
This conversation is sponsored by Resoundant, a Mayo Clinic company and the developers of Magnetic Resonance Elastography. MRE is widely available with over 2000 locations worldwide, and can be done as a low-cost, rapid exam in just 5 minutes. Together with PDFF, this quantitative exam is called an Hepatogram – a powerful non-invasive alternative to liver biopsy in many cases. For more information, visit www.resoundant.com on the web.
This conversation starts with Chris Estes describing the processes he and his colleagues at the Center for Disease Analysis Foundation have used to build a disease model for NAFLD and NASH prevalence in 15 countries. Chris discusses some of the unique challenges that modeling NASH presents. Among other items, these include (a) spontaneous regression of disease; (b) "excess" mortality (mortality not from liver disease where NASH is a contributing factor); and (c) interplay of demographics (gender, age, race, etc.) and co-morbidities (most notably Type 2 diabetes) with disease.
When Chris ends his initial comments, Jörn Schattenberg asks about the viability of using obesity as the anchor for increasing prevalence estimates instead of diabetes, noting the varying definitions of BMI across countries. Chris notes that obesity is imperfect but adds that we have robust, stable, long-term obesity data bases in most countries, whereas diabetes estimates are newer and many people with diabetes to not recognize they have the disease.
The last element in this conversation starts with Alina Allen noting that for clinical trial development, researchers test patients with a range of diagnostics. As a result, they do not need to develop estimates based on (or even linked directly to) obesity or diabetes. Alina asks what models can tell us that can help bring down high placebo rates in double-blinded, placebo-controlled clinical trials. Chris mentions meta analyses as recently as seven years ago that exhibited negative disease progression over time and adds that any assessment of F3 (or even F2) fibrosis is affected by concomitant disease.
This conversation is sponsored by Resoundant Resoundant, a Mayo Clinic company and the developers of Magnetic Resonance Elastography. MRE is widely available with over 2000 locations worldwide, and can be done as a low-cost, rapid exam in just 5 minutes. Together with PDFF, this quantitative exam is called an Hepatogram – a powerful non-invasive alternative to liver biopsy in many cases. For more information, visit www.resoundant.com on the web.
This conversation starts with Chris Estes describing the processes he and his colleagues at the Center for Disease Analysis Foundation have used to build a disease model for NAFLD and NASH prevalence in 15 countries. Chris discusses some of the unique challenges that modeling NASH presents. Among other items, these include (a) spontaneous regression of disease; (b) "excess" mortality (mortality not from liver disease where NASH is a contributing factor); and (c) interplay of demographics (gender, age, race, etc.) and co-morbidities (most notably Type 2 diabetes) with disease.
When Chris ends his initial comments, Jörn Schattenberg asks about the viability of using obesity as the anchor for increasing prevalence estimates instead of diabetes, noting the varying definitions of BMI across countries. Chris notes that obesity is imperfect but adds that we have robust, stable, long-term obesity data bases in most countries, whereas diabetes estimates are newer and many people with diabetes to not recognize they have the disease.
The last element in this conversation starts with Alina Allen noting that for clinical trial development, researchers test patients with a range of diagnostics. As a result, they do not need to develop estimates based on (or even linked directly to) obesity or diabetes. Alina asks what models can tell us that can help bring down high placebo rates in double-blinded, placebo-controlled clinical trials. Chris mentions meta analyses as recently as seven years ago that exhibited negative disease progression over time and adds that any assessment of F3 (or even F2) fibrosis is affected by concomitant disease.
This conversation is sponsored by Resoundant Resoundant, a Mayo Clinic company and the developers of Magnetic Resonance Elastography. MRE is widely available with over 2000 locations worldwide, and can be done as a low-cost, rapid exam in just 5 minutes. Together with PDFF, this quantitative exam is called an Hepatogram – a powerful non-invasive alternative to liver biopsy in many cases. For more information, visit www.resoundant.com on the web.
In Episode 13, we explored ways that data modeling can inform a deeper understanding of the value of community and primary care VCTE screening for NAFLD and NASH. This week, we ask Chris Estes, lead modeler at the Center for Disease Analysis Foundation, what guidance data modeling can provide about diagnostic and drug development.
The episode is a cross between a discussion and an interview-type program. It starts with Chris explaining how he derives models, which variables he selects as proxy measures, why he chooses those, and where shortcomings exist in the data that is available for him to use in populating models. For much of the rest, the other panelists -- Alina Allen, Louise Campbell, Jörn Schattenberg and Roger Green -- either ask questions about how Chris's models work or what we can learn from them, and Chris answers. Beyond that, panelists share their own observations based on research and patient treatment experiences and Chris responds. The group covers a virtual shopping list of topics, including: underreported and misreported diseases; which proxies are more reliable when modeling disease (and which are less so); gaps in current data; positives, negatives and challenges in using obesity as the proxy variable for NAFLD instead of diabetes; the case for treating F2 agents with drugs when they become available; countries most at risk in the coming global NASH pandemic; the need to forecast pediatric NAFLD and NASH better; impact of alcohol consumption on NAFLD or NASH patients; and the situations where regressing fibrosis is pivotal vs. others where simply stopping progression might be a sufficient goal. In the end, this conversation offers a better understanding of how complex modeling is and how remarkable that people like Chris produce results that bear up so well over time.
After the episode, keep listening for an "extra-sode," originally recorded on January 27, 2022, focusing on the practical value and uses of MRE in day-to-day practice. In addition to Louise Campbell and Roger Green, the panel for this extra-sode includes Stephen Harrison, Mazen Noureddin, Kay Pepin from Mayo Clinic and Resoundant, and Scott Reeder from the University of Wisconsin. This discussion, which appears as stand-alone conversation S3 E16.4, addresses the uses of MRE in community settings and the unique benefits MRE can bring as a standalone test and combined with MRI-PDFF in a test/reporting structure known as an hepatogram.
This episode is sponsored by Resoundant, a Mayo Clinic company and the developers of Magnetic Resonance Elastography. MRE is widely available with over 2000 locations worldwide, and can be done as a low-cost, rapid exam in just 5 minutes. Together with PDFF, this quantitative exam is called an Hepatogram – a powerful non-invasive alternative to liver biopsy in many cases. For more information, visit www.resoundant.com on the web.
Last weekend, over 400 liver disease stakeholders gathered in Scottsdale, Arizona for the 2nd Annual Liver Connect Conference, sponsored by the Chronic Liver Disease Foundation (CLDF). The main meeting ran Friday and Saturday and was preceded on Thursday by a half-day session devoted exclusively to NASH (NASH Connect). Episode 15 and its conversations capture some of the thinking that went into the program design and some highlights of the NASH-related sessions.
This conversation starts by focusing on how the meeting was organized. As President Zobair Younossi first explained in Conversation 15.1, CLDF opted for a design that was heavy on group discussions among leading KOLs, light on scientific presentations. In 15.2, Mazen Noureddin talked about having to get through 42 slides in 12 minutes, which left little time for commentary and no time for jokes. So, SurfingNASH asked, how well did the format work.
In the eyes of the panelists (all of whom except Louise Campbell and Roger Green were panelists at the meeting as well), it worked quite well. Marcelo Kugelmas puts it best when he says, "Most of the people that came to the meeting knew what we were talking about, and rather than being put to sleep by a long lecture, they were stimulated by the conversations and back and forth and point counterpoint of those experts that were involved in the different sessions. And I think it happened in pretty much every session."
From there, Roger Green notes that this conference and NASH-TAG, while quite different, "book end" the first quarter quite nicely and then asked what panelists wanted to see as next year's focus. The consensus: drugs if we have approvals (unlikely that quickly); non-invasive tests if not (and then drugs the following year). As the conversation ends panelists appear upbeat both about the conference they just finished and, more important, the future of Fatty Liver disease.
This episode and conversations are sponsored by Madrigal Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company pursuing novel therapeutics for NASH. Madrigal’s lead candidate, resmetirom, is a once daily, oral, thyroid hormone receptor (THR)-β selective agonist that is designed to target key underlying causes of NASH in the liver. Resmetirom is currently being evaluated in two Phase 3 clinical studies, MAESTRO-NASH and MAESTRO- NAFLD-1, designed to demonstrate multiple benefits in patients with NASH. For more information, visit www.madrigalpharma.com.
Last weekend, over 400 liver disease stakeholders gathered in Scottsdale, Arizona for the 2nd Annual Liver Connect Conference, sponsored by the Chronic Liver Disease Foundation (CLDF). The main meeting ran Friday and Saturday and was preceded on Thursday by a half-day session devoted exclusively to NASH (NASH Connect). Episode 15 and its conversations capture some of the thinking that went into the program design and some highlights of the NASH-related sessions.
This conversation continued on the issue of pediatric NASH and NAFLD. Naim Alkhouri discusses the urgent need to include pediatric and adolescent patients in clinical trials, while Louise Campbell asked whether we could possible get results soon enough to help today's youngsters with NAFLD or NASH. Marcelo Kugelmas stated his firm conviction that we need to prove safety and efficacy available, but that there are many other steps we can take (lifefstyle modficiation, for one) if we have adequate commitment. This led Roger Green to note government action in the UK to improve the informational quality of food and fast-food restaurant advertising and to ask whether something similar could happen in the U.S. This led to a discussion about food labelling in the UK, Michele Obama's program in the US, the impact of sugar taxes and food advertising bans during certain times of day, and the overall potential for government activities to succeed. In the end, the group agreed that with money, an advertising campaign to back these kinds of issues might have an excellent result.
The conversation ended with the beginning of a shift to the Saturday session, but first Mazen added a comment about how fantastic it was to have Harvey Alter kick off our Friday morning session.
This episode and conversations are sponsored by Madrigal Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company pursuing novel therapeutics for NASH. Madrigal’s lead candidate, resmetirom, is a once daily, oral, thyroid hormone receptor (THR)-β selective agonist that is designed to target key underlying causes of NASH in the liver. Resmetirom is currently being evaluated in two Phase 3 clinical studies, MAESTRO-NASH and MAESTRO- NAFLD-1, designed to demonstrate multiple benefits in patients with NASH. For more information, visit www.madrigalpharma.com.
Last weekend, over 400 liver disease stakeholders gathered in Scottsdale, Arizona for the 2nd Annual Liver Connect Conference, sponsored by the Chronic Liver Disease Foundation (CLDF). The main meeting ran Friday and Saturday and was preceded on Thursday by a half-day session devoted exclusively to NASH (NASH Connect). Episode 15 and its conversations capture some of the thinking that went into the program design and some highlights of the NASH-related sessions.
This conversation is the full body of a 1:1 interview with Dr. Zobair Younossi, President of CLDF, and SurfingNASH host Roger Green. After Zobair shares information about his background and "fact no one would know if you didn't tell them," the body of the conversation starts with a discussion of what CLDF sought to achieve when the organization started Liver Connect in the first place. After the broader discussion, Zobair went on to discuss why CLDF focused the NASH Connect session Thursday morning on Health Disparities, the importance of non-invasive testing and care pathways and the importance of evidence-based approaches in stratifying patient risk and developing treatment guidelines. Dr. Younossi is a world leader on all these topics, particularly when we focus on public health and epidemiology. This conversation provides a window into his thinking on what we need to do and where NAFLD treatment and advocacy are going.
This episode and conversations are sponsored by Madrigal Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company pursuing novel therapeutics for NASH. Madrigal’s lead candidate, resmetirom, is a once daily, oral, thyroid hormone receptor (THR)-β selective agonist that is designed to target key underlying causes of NASH in the liver. Resmetirom is currently being evaluated in two Phase 3 clinical studies, MAESTRO-NASH and MAESTRO- NAFLD-1, designed to demonstrate multiple benefits in patients with NASH. For more information, visit www.madrigalpharma.com.As much info here as you want
Last weekend, over 400 liver disease stakeholders gathered in Scottsdale, Arizona for the 2nd Annual Liver Connect Conference, sponsored by the Chronic Liver Disease Foundation (CLDF). The main meeting ran Friday and Saturday and was preceded on Thursday by a half-day session devoted exclusively to NASH (NASH Connect). Episode 15 and its conversations capture some of the thinking that went into the program design and some highlights of the NASH-related sessions.
This conversation reviewed Thursday's NASH Connect meeting, which focused on Health Disparities. Panelists discussed their roles in the Thursday presentations and rehashed stories from the other speakers who were on on the podcast. The first part of the NASH Connect program focused on epidemiology by region. The second part of the program centered around talks by Mazen Noureddin, who was part of the podcast, and Stephen Harrison, who was not, on implications of these disparities on testing and treatment. As the group reviewed the program, panelists asked questions about regions or issues they wanted to explore more deeply. Toward the end of this conversation, the talk turned to the high-and-increasing rates of NAFLD and NASH in children and adolescents, what they portend for patients' health as they get older and the value of educating families in reducing the youth Fatty Liver rate.
This episode and conversations are sponsored by Madrigal Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company pursuing novel therapeutics for NASH. Madrigal’s lead candidate, resmetirom, is a once daily, oral, thyroid hormone receptor (THR)-β selective agonist that is designed to target key underlying causes of NASH in the liver. Resmetirom is currently being evaluated in two Phase 3 clinical studies, MAESTRO-NASH and MAESTRO- NAFLD-1, designed to demonstrate multiple benefits in patients with NASH. For more information, visit www.madrigalpharma.com.
Last weekend, over 400 liver disease stakeholders gathered in Scottsdale, Arizona for the 2nd Annual Liver Connect Conference, sponsored by the Chronic Liver Disease Foundation. The main meeting ran Friday and Saturday and was preceded on Thursday by a half-day session devoted exclusively to NASH (NASH Connect). This two-part episode captures some of the thinking that went into the program design and some highlights of the NASH-related sessions.
The episode begins with a 1:1 interview with Zobair Younossi, President of CLDF and Surfing the NASH Tsunami Host Roger Green. This discussion starts with Zobair describing the goal of Liver Connect: to serve as vehicle between different medical specialties, between medicine and industry, and even between both groups and patients, in terms of practical issues in treating the most important liver diseases. The discussion pivots to the question why the NASH Connect session was devoted to global Health Disparities and the multiple factors that drove the decision. The last reason Zobair gave was the low level of NAFLD awareness and activity around the world, which transitioned into a discussion about the need for stronger programs in virtually every country and the parallel need to appreciate that we need the entire spectrum of relevant providers -- dieticians, nutritionists, primary care physicians among others -- to engage in fighting this coming pandemic. In the end, Zobair stated his belief that we will accumulate evidence on how to proceed and that good evidence will define our path forward.
The rest of the episode is a panel session with CLDF Vice President Marcelo Kugelmas, event speakers Naim Alkhouri and Mazen Noureddin, Louise Campbell and Roger Green. The group reviews the Thursday Health Disparities session, which included one discussion global disparities in regional disease burden and another on global disease epidemiology and another on disparities in the source of disease and treatment and testing results. Panelists followed this by reviewing the Saturday session, which included two large group discussions. one on non-invasive testing and another on treatment.
The Liver Connect conference was an opportunity to discuss trends in thinking and explore common perspectives. This episode incorporate the same vision into an invigorating discussion.
This episode is sponsored by Madrigal Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company pursuing novel therapeutics for NASH. Madrigal’s lead candidate, resmetirom, is a once daily, oral, thyroid hormone receptor (THR)-β selective agonist that is designed to target key underlying causes of NASH in the liver. Resmetirom is currently being evaluated in two Phase 3 clinical studies, MAESTRO-NASH and MAESTRO- NAFLD-1, designed to demonstrate multiple benefits in patients with NASH. For more information, visit www.madrigalpharma.com.
The episode and this conversation is sponsored by HistoIndex. This specific conversation focuses on ways and AI-assistive technologies and analyses can improve our abilities to assess efficacy in drugs that treat advanced fibrosis and cirrhosis.
For this extrasode, HistoIndex Chief Scientific Officer Dean Tai joins Quentin Anstee, Mazen Noureddin, Joern Schattenberg and Roger Green to discuss how AI-based algorithms can support improved analysis of ballooned hepatocyte changes both in advanced fibrosis and cirrhosis patients.
The rest of the conversation probes how this work will affect diagnosis and drug development, what other tests panelists can foresee and areas where Histoindex is looking to create new algorithms and improve existing ones.
This conversation starts with Histoindex Chief Scientific Officer Dean Tai discussing the approach his company takes to AI-assisted hepatopathology. Dean starts by discussing briefly how staining, which is extremely helpful when the goal is to define the individual patient, becomes one more source of error in the more quantitative approach necessary for drug trials. He goes on to point out that while they can achieve 90% success in reproducing an individual coder's result using AI, their goal is to achieve 99% success. He finishes by defining the goal as "majority-agreed hepatocytes," hepatocytes where 5 or more of the 9 pathologists in the initial exercise agreed that a hepatocyte had ballooned. As Dean puts it, with ballooned hepatocytes, "you are really trying to identify bad apples from all apples," not "oranges from apples."
In explaining the Histoindex approach, Dean describes some pathologists as "under-callers" who identify relatively few ballooned cells and others as "over-callers" who identify far more cells. The primary difference between the two groups was how large they needed a cell to be before they classed it as "ballooned."
Because these differences were systematic and structural, Quentin questions whether we can ever "train" consistent responses. He suggests that consistency will grow for a while but then coders will revert more to their historical patterns. In response to a question from Mazen, Quentin goes on to note that the number of pathologists necessary to validate a ballooned cell will vary inversely with the number of cells identified. For example, a model based on 7-member agreement produces results that are more specific, less sensitive. A model based on 3-member agreement would produce more sensitivity, less specificity. As a result, the team settled on 5 (majority of 9) as the best-rounded number. Mazen responds that for drug trials, being more specific is preferable because it creates a better chance for the drug to appear efficacious when it is.
The panelists go on to note that this tool is extremely helpful today in Phase 2, but not in Phase 3 and Dean explains some of the concepts Histoindex is working on to support future use in Phase 3 trials.
At that point, the conversation shifts to having Mazen discuss his work in cirrhosis. Going back through historic work, and particularly separate work from Drs. Garcia-Tsao and Younossi, Mazen identified three features to track: septal thickness, nodular features and fibrosis area (the SNOF score). Using these metrics Mazen sought data from the Galectin trials because these were among the few trials that measures portal pressures. The Galectin data allowed researchers to correlate these kinds of measures to a 20% change in portal pressures. This score wound up being reliable in detecting portal hypertension and in two particularly pivotal measures: detecting presence of varices and changes of greater than 20% in portal pressures.
One major discussion at NASH-TAG this year was about the inconsistency in ballooned hepatocyte identification and how this inconsistency inflates screen fail rates and possibly placebo response across studies. This conversation is part of a thorough exploration of this issue.
This conversation starts with Roger Green wrapping up the earlier discussion of the relationship between holistic NASH assessment and ballooned hepatocyte scoring by saying it is not surprising that fibrosis is an element in ballooned cell scoring, given that pathologists start with a holistic assessment and work back from there.
Jörn Schattenberg asks Quentin Anstee to comment on Stephen Harrison's proposal to use 3 slides for H & E reads. After discussing a different strategy ("keep reading until you see enough cells"), Quentin suggests a protocol with a constant, relatively small number of slides for each case. Roger then asks Quentin how many ballooned cells might appear on a single slide; Quentin answers that this is a challenging question but on the slide where everyone saw the most ballooned cells, the number scored by an individual pathologist ranged from 45 to 225. After Louise Campbell comments on the need to make the best possible use of tissue out of respect to the patient who is donating the biopsy, Roger asks a final question: a year or two from now, what is likely to be different and what can we aspire to be different as a result of this study. Quentin would like to see ballooned hepatocyte assessment move from a "Yes/No" assessment to a continuous assessment of volume and would like to see regulators recognize the role and value of AI-assistive technologies in drug development. Mazen Noureddin concurs and goes on to ask what we might expect in terms of changes in the screen fail rate. In different ways and with different nuances, Jörn, Louise and Roger concur as well.
The episode and this conversation are sponsored by HistoIndex. Conversation 14.5 is a discussion of how artificial intelligence driven assistive technology can improve the consistency of ballooned hepatocyte scoring in advanced fibrosis and support development of robust outcomes for fibrosis studies.
One major discussion at NASH-TAG this year was about the inconsistency in ballooned hepatocyte identification and how this inconsistency inflates screen fail rates and possibly placebo response across studies. This conversation is part of a thorough exploration of this issue.
This conversation starts with Roger Green asking Stephen Harrison how clinical trial analysis might change for the better pending implementation of what researchers learned in this study. Stephen suggests that the area in greatest need of improvement is efficacy analysis at the back end of clinical trials. Specifically Stephen notes that variability in placebo response rates is the single largest factor determining which Phase 2b and Phase 3 trials are deemed success or failure.
He asks whether there is a way to correlate the AI assessment of ballooned hepatocyte improvement to changes in fibrosis and, separately, whether we should be looking at more tissue. Stephen notes that the present approach has led us to kill good drugs due to analytical error. Louise Campbell agrees and makes a different point, which is that over time, exhaustion leads to consistent changes in the ways experts evaluate data.
Quentin takes Louise's point as an interesting question about controlling for intra-rater variability. After some interplay, Stephen discusses how he was trained to read slides (by Dr. Brunt, lead author on this paper). He was taught first to get an overall feel for whether the slide architecture looks like NASH before scouring for ballooned hepatocytes. Quentin notes that the AI methodology (qBallooning2) incorporates some assessment of fibrosis into the identification of balloon cells.
The episode and this conversation are sponsored by HistoIndex. Conversation 14.5 is a discussion of how artificial intelligence driven assistive technology can improve the consistency of ballooned hepatocyte scoring in advanced fibrosis and support development of robust outcomes for fibrosis studies.
One major discussion at NASH-TAG this year was about the inconsistency in ballooned hepatocyte identification and how this inconsistency inflates screen fail rates and possibly placebo response across studies.
This conversation is part of a thorough exploration of this issue. It starts with Mazen Noureddin raising two questions about the entire subject of ballooned hepatocyte scoring in NAS assessment: should we use it at all, and if we should, should we move immediately to AI as the key to analysis?
Quentin provides nuanced answers to both questions. On the issue of ballooned hepatocytes, he notes that these were originally designated to characterize individual patients, not to create semi-quantitative scores. Today, he notes, we are asking far more of ballooned hepatocyte assessment than it was designed to do. On the issue of AI, Quentin notes his care to use the phrase "AI-assisted tehcnology," that we need pathologists to confirm that what the patient has is, in fact, NAFLd instead of, for example, autoimmune hepatitis. Once that is proven, then we can ask AI to provide a more quantiatively consistent assessment.
Jörn Schattenberg begins his comments by noting and agreeing with the idea that we are asking more of ballooned hepatocyte assessment than it was designed to do. He proceeds to ask whether we can augment hepatocyte analysis with a liquid biomarker or with a different stain.
Quentin suggests that the solution will not lie in stains. The idea or liquid biomarkers is more promising, but first we will need to reduce error in the assessment and then focus our attention on biomarkers (he mentions NIS-4) that were designed to assess hepatocytes.
Roger Green finishes this conversation by noting the the phrase "semi-quantitative" itself invites analytical error. We power studies assuming that the important error is statistical and can be resolved by sample size, whereas the bigger challenge is in the qualitative assessment of the slides. If qualitative variability is dramatic, as it is here, it will dwarf statistical error and mean that all samples are underpowered. Roger concludes by asking whether we should forestall major shifts until we understand how much we can reduce analytical error through AI assistance. Quentin concurs.
The episode and this conversation are sponsored by HistoIndex. Conversation 14.5 is a discussion of how artificial intelligence driven assistive technology can improve the consistency of ballooned hepatocyte scoring in advanced fibrosis and support development of robust outcomes for fibrosis studies.
One major discussion at NASH-TAG this year was about the inconsistency in ballooned hepatocyte identification and how this inconsistency inflates screen fail rates and possibly placebo response across studies.
This conversation explores that issue in detail. It begins with Quentin Anstee eloquently laying out the challenge that led to this study and the approach it took.
The challenge: recent studies have produce Kappa values for coding NAS scores in the 0.55 - 0.60 range. These scores suggests a level of error-related noise that might swamp a signal that a drug actually works.
The solution: nine of the world's leading hepatopathologists (who, Quentin notes, were "amazingly generous with their time") scored ten different liver biopsies by drawing circles around the slides they determined were ballooned cells and then repeated the process 90 days later in a different order, with some mirrored or rotated.
First finding: Concordance was "relatively modest." There was only one slide in the entire exercise where all nine pathologists found a ballooned hepatocyte. This clearly suggested that relying on a measure of the number of ballooned cells on a slide as a measure of disease was likely to produce inconsistent results due to what Quentin describes as "the lack of a common vocabulary" or vision between the pathologists.
After noting how small a sample a single cell was, Stephen Harrison asks whether we would be served better if we evaluated the volume of ballooned cells on a slide, rather than the absolute number.
As the conversation ends, Quentin notes analyzing a slide looking for ballooned cell is a much more complex procedure than nonhepatologists previously appreciated. He suggests that if we are looking for an analysis that is quantitative and consistent, volume may provide more robust results than looking at an actual number.
The episode and this conversation are sponsored by HistoIndex. Conversation 14.5 is a discussion of how artificial intelligence driven assistive technology can improve the consistency of ballooned hepatocyte scoring in advanced fibrosis and support development of robust outcomes for fibrosis studies.
One major discussion at NASH-TAG this year was about the inconsistency in ballooned hepatocyte identification and how this inconsistency inflates screen fail rates and possibly placebo response across studies. This episode explores that issue in detail.
The episode is sponsored by HistoIndex. At the back of the episode is a discussion of how artificial intelligence driven assistive technology can improve the consistency of ballooned hepatocyte scoring in advanced fibrosis and support development of robust outcomes for fibrosis studies.
This conversation includes three of the paper's authors, including last author Quentin Anstee. The conversation starts with Professor Anstee discussing how the paper came to be. He quickly jumps into the meet of the discussion, which is the relatively low concordance between highly skilled world class hepatopathologists over how many ballooned hepatocytes they see on a slide of a patient who might have NASH. The results suggested significant differences between two world-class hepatopathologists looking at the same slide in terms of the presence and significance of hepatocytes.
The next stage of the episode consists of other panelists praising the study while asking questions about its implications. Stephen Harrison asks how we can take these findings into drug development. Mazen Noureddin asks whether these results suggest either that we should question using ballooned hepatocytes in drug development or, more likely, we should shift immediately to an AI-mediated solution to get more consistent results. Jörn Schattenberg asks whether liquid biopsies would improve prediction and, presciently, whether we are asking more from liver histology than it can deliver.
This points to a pivotal issue: liver histology was developed initially to characterize individual patients qualitatively. Today, we call these findings "semi-quantitative" and use them to analyze trial results.
Two problems: the error embedded in the differences between how two pathologists would interpret the same slide is far greater than the sampling error, leading us to undersample and overinterpret. Second, we try to "prove" the value of blood-based biomarkers and AI-based assistive technologies by comparing them to something that is deeply flawed in the first place.
The extrasode discusses how HistoIndex used created the qBallooning2 analysis to improve the common identification of ballooned hepatocytes in patients with advanced fibrosis. In addition, Mazen Nourediin discussed his AASLD Poster of Distinction from 2022, which looks at ways that artificial intelligence techniques can support more robust analysis of improved outcomes in patients with cirrhosis.
In the end, though, no 4,000 character summary can do this episode justice. To fully get the impact of this critically important discussion, plan to listen at least twice. Listen to the first part to comprehend the scope of the issue around ballooned hepatocytes and the challenges it causes, and the second part to learn how inventive data scientists can create better solutions by processing large amounts of data and being willing to challenge historical assumptions.
NOTE: HistoIndex is sponsoring a complementary webinar, Deciphering NASH: Fibrosis Dynamics in Cirrhotic Patients and Insights into Ballooned Hepatocytes using AI, at 11:00 am Eastern Daylight Time on Tuesday, March 23. For more information, visit the event website athttps://www.global-engage.com/event/nash-data-on-fibrosis-and-ballooning-using-ai/.
Episode 13 looks at the NICE Draft Guidance Evaluating FibroScan use in Community and Primary Care settings. This conversation focuses on underlying tensions between a methodology designed to assess big-ticket spending on critical moments of disease and a population screening approach that centers on wellness care more than illness care.
This conversation starts with Roger Green noting an inherent tension between short-term health economic tests driving a decision not to compensate and longer-term healthcare priorities that rely on patients who cannot afford the test being able to take it. Ian Rowe describes this as a tension inherent in the UK system and therefore, not a "real issue." In contrast, Jörn Schattenberg notes a significant structural issue in that, as Ian noted earlier, NICE relies on companies to provide the necessary data, but the costs of providing that data might be excessive for a small diagnostics company like Echosens, although not for a major drug company. Jörn goes on to raise the issue of reimbursing wellness vs. illness; this is an economics of illness analysis done for a process that enhances wellness. Louise Campbell suggests a parallel analysis of the cost of expensive HCC drugs like sorafenib that are highly costly but provide only 3-6 months added longevity. In the end, Roger Green asks one thing each participant would like to see vs. something they are confident they will see. Answers vary, but they suggest that the current system is not a particularly effective way to assess this kind of analysis and that, beyond that, this specific analysis might benefit from some different looks at data. In the end, Louise Campbell notes that the comment period ends on March 9 and invites as many people as possible to comment before then.
Episode 13 looks at the NICE Draft Guidance Evaluating FibroScan use in Community and Primary Care settings. This conversation focuses on the real impact of a decision not to compensate at this time, with most discussion centering in some form around the idea that a positive NAFLD screen leads to what Chris Estes of the Center for Disease Analysis Foundation describes as a "Cascade of Care."
Jörn Schattenberg leads this conversation by asking whether we can use an entry test or some other method to enrich the test and thereby speed development of the data necessary to answer the question. Chris Estes points out that the right analysis will require assessment of the entire care cascade, with all its tests and care for people who test positive. Roger Green asks Chris whether such data exists in another setting where we can extrapolate to this situation, to which Chris notes that the FibroScan studies are fairly early and done only in tertiary care centers. Louise Campbell asks Chris whether any post-COVID modeling has been done given that the downstream burdens COVID is placing on the healthcare system due to diseases being diagnosed later in course of disease. Chris refers to some viral hepatitis analysis that suggests that while analysts initially assumed a two-year lag in care due to COVID, the actual impacts on care and costs appear to last far longer. The rest of the discussion bounces back and forth between the question how to apply data that lead to clear inferences but is not directly applicable to this case and the lack of the continuum of data necessary to make clean comparisons. At the end, Louise Campbell suggests that a decision not to compensate will way most heavily on economically burdened and rural patients. Roger Green asks whether this becomes one more health burden on people who already have not received enough care and Chris Estes describes this combination of inability to travel and incur costs of care with COVID, the dramatic increases in opioid addiction in this population, and well-noted increases in drinking and obesity to create a "perfect storm" of risk factors.
Episode 13 looks at the NICE Draft Guidance Evaluating FibroScan use in Community and Primary Care settings. This conversation focuses on some of the data issues surrounding this evaluation, ranging from the lack of the long-term data necessary to make the wellness case to narrower, more case-specific flaws in how costing data was developed.
The previous conversation looks at how NICE analyzes procedures and ways this approach might conflict with the economics of NAFLD screening. This conversation starts with Ian Rowe noting that NICE depends on the manufacturer to provide data for the analysis, but Echosens only presented one year data. Louise Campbell asks if advocates could put forward some of the Hepatitis C data to address the issue, but, as Ian points out, FibroScan is the index diagnostic for NAFLD; in contrast, it was used for disease staging in Hep C. Jörn Schattenberg joins the conversation to note ways in which Germany and the UK are similar in terms of the relationship between reimbursement and use and other ways in which they are different. Eventually, Jörn points out, we will have 10-year data, but he asks how this can benefit patients today. Louise suggests that data and analyses exist in other settings that can help address these issues for NICE, particularly if we consider biopsy (and its costs) as the option. Ian Rowe asks "a couple of questions from the NICE perspective," which make the point that this kind of screening probably is desirable but must be carefully managed because once tests are made available more widely, people will sign up quickly, backlogs will ensue and practices will be challenged and may wind up needing to add staff. Louise acknowledges all this and notes that this analysis places a higher training burden on the manufacturer than Phillips or GE face with ultrasound.
Episode 13 looks at the NICE Draft Guidance Evaluating FibroScan use in Community and Primary Care settings. This conversation focuses on the basic way that NICE approaches issues like this one and tensions between that approach and the health and wellness outcomes this kind of screening might provide.
As Roger Green mentions when starting this conversation, Surfing the NASH Tsunami usually advocates for early prevention and wellness care as key strategies for fighting the coming NASH pandemic. The issue is that NICE answers relatively specific questions using rigorous cost analyses. At this point in time, the caliber of longitudinal data necessary to make the optimal case for FibroScan simply does not exist.
After Roger describes the underlying issue, Ian Rowe focuses the conversation by discussing the approach that NICE takes to health economic analysis. Along the way, he notes that in cases like this one, the correct application of this generally valuable analysis might not lead to the best outcome in terms of the health of patients. Louise Campbell goes on to discuss three ways that this particular analysis fails to capture the situation accurately: (i) the test was viewed in a vacuum instead of in the context of the care it would trigger; (ii) the testing frequency was based solely on tests done in radiology departments, which appear to account for a small percentage of all FibroScan tests done in the UK; and (iii) it assumed uniform costing for FibroScan tests done in a radiology department, whereas Louise was able to point through personal experience to the deviations (both from the analysis and from each other) from the numbers used in the analysis. This conversation ends with Chris Estes discusses the idea that this should be a model of long-term inputs and outputs reflecting not only the cost of the test but also the costs and benefits of the downstream care that would result from testing.
The UK's National Institute for Health and Care Excellence (NICE) issues health economics-based decisions on whether therapies and diagnostics should be reimbursed by the British government. In a recent draft guidance titled FibroScan for assessing liver fibrosis and cirrhosis outside secondary and specialist care, NICE has stated that "there is not enough certainty for [using FibroScan to assess liver fibrosis or cirrhosis for adults in primary or community care] to recommend it as a clinically effective and cost saving option for routine use." This episode centers around understanding the draft guidance and what it means for out of hospital screening.
In addition to Louise, Jörn Schattenberg, Ian Rowe and Roger, this panel includes a first-time: lead modeler and epidemiologist Chris Estes of the Center for Disease Analysis Foundation. Chris has been lead modeler on some of the 2015-2030 projects previously discussed on the podcast.
The question driving this episode is: what about the NICE decision makes sense and what might not. Ian started by providing context about NICE: its mission is to "allow 'rational' in inverted commas decisions to be made about health care spend, mostly from a cost effectiveness and clinical effectiveness perspective." He noted that this decision revolves around a fairly narrow target: FibroScan in a community or primary setting, as compared to its delivery or secondary care. Ian goes on to note that two sets of data that would help drive a decision are scarce: how well the test works and, separately, how well learning test results causes patients to improve their health. Against that backdrop, he noted that a decision not to fund might be "regrettable" and not in the interest of patients, but a logical outcome of the presenting question, organizational mission and lack of existing data.
Louise Campbell followed Ian and question some specifics of how the analysis was conducted and the source and nature of cost data NICE used. On the "nature of data" issue, she noted that the NICE review team presented FibroScan costs as a single, fixed variable, whereas in the "real world," the ways and amounts that different institutions charge vary widely.
Roger Green then broadened the question to ask what the outcome might be with a broader question or approach the economics of the situation. Chris Estes discussed the direct and indirect costs that would go into a complete calculation and then to note that if you could prevent disease before it began (by addressing obesity or early NAFLD, this would be the most cost effective strategy. Ian noted it was also one on which the manufacturer seemed unable to provide data.
The rest of the episode focused on issues such as how this question would be treated differently in Germany, what data sources or facts might drive a different decision and how to research or acquire this data. Louise noted several examples of areas where she felt the costing analysis might not have reflected the realities of the market and patient care cases. The conversation jumps from one topic to another. Toward the end, Jörn notes that while our primary focus should be to support wellness, the easier economics to evaluate are those of treating illness and it becomes clear that this tension between illness that provides hard data and wellness that is a softer measure but clearly of greater benefit to society is a significant source of friction that tends to undercut long-term thinking.
Throughout this podcast, panelists uncovered a large set of actions that might improve NASH care for those Black Americans who have the disease while suggesting a range of solutions, some more realistic or faster to achieve than others. In this conversation, each panelist is asked to mention one thing they believe might actually improve within the next year. A few focus on 3-5 year fixes, but most offer a progress steps that can be attainable within the next year if enough of the right people dedicate focus to them.
Suggestions include: looking at epigenetics to determine whether there are non-Hispanic Black American families with genetic markers for disease and how these may be addressed through diet and other lifetsyle issues (Zaki Sherif); organizing a disciplinary group inside NIH to fund a multi-center study on this issue (Donna Cryer); ensuring that NAIL-NIT and other trials that are currently in recruitment phase include a large enough subsample to study this population (Louise Campbell); developing and beginning to implement plans for specific activities that will reduce health inequity (Ani Kardashian); separately, (i) for drug companies to invest in learning the specific issues related to NASH that affect this community and (ii) empowering patients through education and outreach (Yani Adere); and enable Global Liver Institute and other organizations to become "clearinghouse[s]" for good ideas to flourish in efforts that attract groups with common interests and focus to this larger conversation (Roger Green).
With so many major clinical trials for Fatty Liver drugs recruiting over the next couple of years, we have an opportunity to study effects on Black Americans from inception, instead of assuming these drugs work the same in different racial groups only to find, some years later, that we were wrong.
This conversation explores historical reasons for underrepresentation and shares possible reasons or steps to remedy this issue in a timely fashion. It starts with Ani Kardashian echoing points that other panelists made earlier in the episode about the need to enrich clinical trials with larger shares of non-Hispanic Black patients so that we can learn about how the disease is different in this group than in other sub-populations. In response to a question from Roger Green, Donna Cryer traces a chain of actions to address the issue: corporate drug developers ask their CROs how to ensure large enough representation in the sample. CROs reach out to community groups that have credibility with community leaders and members to recruit. "People who look like me" take researchers into their communities to certify the researchers' credibility. Louise Campbell confirms this vision by discussing research with Aborigines in Australia. The rest of the conversation centers around three topics: (i) the role International NASH Day can play in providing education on this issue, (ii) the challenges that occur because front-line physicians in hospitals with large proportions of non-Hispanic black patients do not screen patients for Fatty Liver, and (iii) challenges, opportunities and strategies involved in attempting to screen patients for Fatty Liver when they visit hospitals and clinics for other diseases.
Factors that make treating NASH and NAFLD a unique challenge for non-Hispanic Black Americans range from Social Determinants of Health (SDOH) to omics suggesting that the disease in Black Americans may be different than in Caucasians or a range of behavioral elements (for example, smoking) that are more closely associated with Black Americans.
This conversation begins with Stephen Harrison noting that a combination of lower incidence of Fatty Liver disease within this population and an historically appropriate trust deficit that non-Hispanic Black Americans feel toward medical trials leads to study samples without enough sample to tell us whether a given diagnostic or course of therapy works better or worse in a non-Hispanic Black American population. As a result, he notes, we do not know how negative health behaviors like smoking or alcohol, genomic patterns and comorbidities affect liver health in this population. Later on, Zaki Sherif notes that in omics work in HCC, he and colleagues identified metabolites that upregulated in Caucasians and down-regulated in Blacks. All this culminated in Donna Cryer's point that this is an historic moment to enrich non-Hispanic Black American populations in these trials so that from the moment we begin using these drugs in the general population, we will know how these drugs work among Blacks instead of simply "assuming" they work as they do with other racial groups, only to lear 5-10 years later than this is wrong.
How do you discuss a disease with no history during Black History month? Surfing the NASH Tsunami asked, "What challenges exist for non-Hispanic Black Americans in the areas of NAFLD and NASH, given how low incidence is?" In this conversation, a corporate executive, not-for-profit patient champion and academic researcher discuss some of the reasons it is so important to identify and address these issues today.
Yani Adere, NASH MSL at Novo Nordisk and the person who pitched the episode idea to Roger Green, kicks off this conversation by discussing issues that concern and motivate her, She notes that even with lower incidence than other racial groups, NASH is still the second leading cause of liver transplant in non-Hispanic blacks and that the course of the disease is similar in black and Caucasians. Next, Global Liver Institute Founder and CEO Donna Cryer notes that since NASH is a disease without much history, we can make Black History in realtime by introducing clinical trial protocols, treatment modalities and population screening programs that address specific challenges facing that community. Next, Dr. Zaki Sherif of Howard University notes that end-stage liver disease in non-Hispanic Black communities has two challenges: faster progression from cirrhosis to HCC than other groups and lower likelihood to receive a liver transplant. During the rest of this conversation, Dr. Ani Kardashian of the Keck School of Medicine at USC, Zaki and Donna comment on several addressable issues that explain why liver outcomes are lower for non-Hispanic Blacks than for other racial groups.
In recognition of Black History Month, SurfingNASH looks at how the impact of NASH on non-Hispanic Black Americans differs from other groups. The episode includes Key Opinion Leaders not only in Fatty Liver disease but also, more broadly, social determinants of health like food insufficiency and clinical trial participation.
This episode was originally suggested by Dr. Yani Adere, a Medical Science Liaison at Novo Nordisk and long-time SurfingNASH listener. Yani set the stage for this conversation by noting that while incidence of NASH and NASH cirrhosis may be relatively low among non-Hispanic Black Americans, those who get the disease progress at the same rate as other ethnic groups and, in fact, Fatty Liver is the 2nd leading cause of cirrhosis in this population. She concludes by noting that Social Determinants of Health (SDOH) create undue burdens for Black Americans with liver disease as with other diseases.
Donna Cryer, Founder and CEO of the Global Liver Institute followed Yani. First, she noted that since NASH has a limited history as a disease, it offers the chance to create history by building health equity into clinical trials and patient treatment as initial protocols and guidelines come into force, "instead of waiting 5-10 years" as with other diseases.
Dr. Zaki Sherif of Howard University raised an important point about Liver Disease in this community: while non-Hispanic Black Americans progress from liver to cirrhosis slowly (as do other groups), the speed at which they progress from cirrhosis to HCC is faster...and Black Americans are less likely and slower to receive liver transplants.
Dr. Ani Kardashian of USC, a transplant hepatologist and national leader on the issue of food insufficiency, began her comments by nothing that while Fatty Liver disease is not as common in Black Americans, outcomes are poorer. Ani raises the issue that some of the poorer outcomes might result from lower levels of patients in clinical trials, which is a challenge with many diseases.
From here, the discussion heads off in several different directions, all of which confirm the point that the intersection of relatively low incidence, other diseases with higher prevalence and severe outcomes and the range of SDOH issue leads to a situation where patients receive less treatment and support than other sub-populations. The group discusses some of the major challenges and posits possible solutions.
This wrap-up conversation of our NAIL-NIT episode provides greater detail on NAIL-NIT's research plan. The plan itself includes two elements: a retrospective analysis of data collected to date by drug developers in their own clinical development programs and a six-year prospective study currently estimated to include 1,000 - 1,300 patients, with major adverse liver outcomes (MALOs) anticipated to report in four years and final results in six.
In response to a question, Mazen Noureddin suggested that we might see some significant guidance to drug developers and manufacturers within a year on the topic of screen failure rates. Over time, the retrospective data will also afford the opportunity to test some of the newer composite test measures like FAST and MAST against larger samples of patients. Sen Sundaram expressed a different target for one-year results: guidance from one or more regulatory agencies about how many patients they will want to see in key clinical trial patient cohorts and sub-populations.
In terms of the prospective studies, Louise Campbell asked whether certain segments of patients who had screened out of previous studies would be appropriate for the prospective sample. Stephen Harrison noted that one particular clinical trial, North Sea Therapeutics, included over 100 patients with F3 and NAS of 3 but no balloon hepatocytes. He also noted that by using the Summit Clinical Trial network to recruit a significant share of patients, they would be recruiting a significant share of patients through community trial sites, which can produce patients faster than academic sites. In response to the closing question, NAIL-NIT panelists made a plea for more companies to join this effort.
The conversation looks at how the NAIL-NIT program design improves on the quality of insight provided by the NAS score, both in terms of drug development and treatment of individual patients. Also, note that during this conversation, Mazen Noureddin thanks a relatively large group of individuals and companies supporting this project.
The first section focuses mostly on what we can and cannot learn from a NAS score, and implications of its shortcomings on the drug development process. After this, Stephen Harrison notes the complex role the liver plays in energy transfer throughout the entire metabolic process. This suggests that the effects of Fatty Liver disease vary among individual patients and, as a result, drug development and patient diagnosis and treatment should provide sufficient insight to optimize each patient's therapy. As the conversation closes, Mazen Noureddin is responding to a question from Louise Campbell about what we will learn about optimal testing strategy. Mazen suggests there is unlikely to be a single "winning" test but, instead, a combination of NITs probably will be necessary to answer all the questions necessary to optimize therapy.
NAIL-NIT is both a response to the challenges of histopathology and an effort to create a different vision of testing liver patients.
This episode starts with Stephen Harrison describing the events that came to demonstrate how challenging current histopathology approaches: a series of drug development failures that reflect shortcomings in methodology rather than in the developmental drugs themselves. Sen Sundaram notes that the difference between the NAIL-NIT approach and that of other consortia is that NAIL-NIT seeks to link NITs directly to outcomes rather than correlating them to histopathology-based measures. Mazen Noureddin discussed the frequency at which patients with obvious NASH and fibrosis fail to screen into studies due to inability to find balloon hepatocytes in the biopsy-derived slides and raises the human ethical implications of excluding these patients. Amy Articolo encourages us to envision a future in which drugs are available to treat patients and make sure we have the best possible testing to diagnose and prescribe the proper therapeutic regimens to patients. From there, the discuss shifts as Stephen Harrison and Sen Sundaram discuss the quality of data existing today that links NITs directly to outcomes. Sen notes that "if we think about the amount of data that we have" for NITs and outcomes, "we probably have more data now than is cited to support histopathology in a current guidance."
NAIL-NIT is a new NAFLD consortium dedicated to exploring the direct relationship between non-invasive testing (NITs) and outcomes in Fatty Liver disease. In this opening conversation, study co-directors Stephen Harrison and Mazen Noureddin are joined by Steering Committee members Amy Articolo, Medical Director for NASH at Novo Nordisk and Senthil Sundaram, CEO of Terns Pharmaceuticals.
One at a time, the four panelists describe their motivations for forming and becoming a part of this consortium. Mazen Noureddin talks about the group's common goal to produce data that will shape a shift from biopsy-derived drug approval analyses to NITs. Stephen Harrison describes the group's strategy and two main efforts: retrospective analysis of the significant amount of available data that link NITs and outcomes, and a prospective study to be conducted over the next 4-6 years designed to establish correlations and links to outcomes not only for individual tests, for also for combinations of NITs. Sen Sundaram discussed his earlier work with a similar consortium that asked the same kinds of questions about PBC and demonstrated that alkaline phosphatase could provide the analyses necessary for drug approval. Finally, Amy Articolo starts by noting that she has transitioned from a full-time treating OB/GYN to a corporate executive and brought with her a "passion" for "patient-driven, patient-centric care" and several ways that supporting analysis driven entirely by NITs can support support that passion.
The NAIL-NIT initiative has potential to transform how we evaluate drugs for approval and patients throughout the course of their disease. This is an important episode (and conversation) for anyone with a personal or professional stake in simplifying the NASH/NAFLD drug development process while simultaneously improving the quality of data for regulators and treating physicians alike.
Co-director Mazen Noureddin and Steering Committee members Amy Articolo of Novo Nordisk and Senthil Sundaram of Terns Pharmaceuticals join the Surfers (Stephen Harrison is also a co-director) to discuss the NAIL-NIT Consortium, an ambitious effort to link non-invasive testing (and specific tests) directly to outcomes.
NAIL-NIT's activities include a prospective six-year study of 1,000 - 1,300 patients and, separately, retrospective analysis of thousands more cases to establish the best ways to make use of the growing array of non-invasive testing methods in the treatment, diagnosis, and monitoring of NASH patients.
Participants in this episode anticipate that the retrospective element will start generating elements within one year, and the prospective within four years. They describe the program's goals as being practical and business-like (better drug and NIT development), but also profoundly human (never denying a patient with clear F3 fibrosis access to a trial because the pathologist could not find a balloon hepatocyte on the cell.
Episode 10 dives into recent NAFLD and NASH Prevalence studies in the US, UK and Germany and explores what this can tell us about who to screen for NAFLD and NASH, when to screen first and how often to screen after that.
This wrap-up conversation wrestles with the question who to screen, when to start and how to reckon with the dual challenge that the early effects of Fatty Liver disease are more about metabolism than liver per se and that there are not enough hepatologists to treat everyone with Fatty Livers. The group's conclusion: we need to test more and earlier, but do not have enough data yet to tell us exactly how to implement this very, very high level statement.
Episode 10 dives into recent NAFLD and NASH Prevalence studies in the US, UK and Germany and explores what this can tell us about who to screen for NAFLD and NASH, when to screen first and how often to screen after that. This conversation asks what we can learn from trial results and, separately, the clinical experiences of practitioners and patients about the value of early testing and also testing in the context of education vs. medical care.
A brief introduction cannot do this short conversation justice, but the key point is not a surprise: patients who engage in testing based on education are more engaged in results and different kinds of therapy (including lifestyle) than those who go to the doctor, do bloodwork and learn they have a problem.
Episode 10 dives into recent NAFLD and NASH Prevalence studies in the US, UK and Germany and explores what this can tell us about who to screen for NAFLD and NASH, when to screen first and how often to screen after that. This conversation focuses on the paper Screening for undiagnosed NAFLD and NASH: A population-based risk factor assessment using Vibration-Controlled Transient Elastography (VCTE), which was published last November in the refereed journal PLOS ONE.
Lead author Wayne Eskridge describes the study and presents key findings. In this conversation, two of the striking points he raises about the study are: (1) that relatively high percentages of study participants, volunteers with no previous history of liver disease, exhibited different levels of liver fat and even disease; and (2) that many of these were patients in their 40s as compared to the 50s and 60s where we more conventionally think about disease. After the group shared some concepts and numbers, participants agreed that the number of adults exhibiting some level of fatty liver with an accompanying metabolic challenge is 3 in 8.
Episode 10 dives into recent NAFLD and NASH Prevalence studies in the US, UK and Germany and explores what this can tell us about who to screen for NAFLD and NASH, when to screen first and how often to screen after that. This conversation focuses on the paper Prevalence and Risk Factors of Advanced Liver Fibrosis in a Population-Based Study in Germany, which was published last Saturday in Hepatology Communications.
Last author Jörn Schattenberg presents results of the paper, after which panelist Ian Rowe and Wayne Eskridge ask the role that FIB-4 played in the study and analysis and Roger Green asks Professor Schattenberg what significance to apply to a Fatty Liver Index >60 in 3/8 of the sample.
This episode looks at four different sources of data estimating NASH and NAFLD prevalence in population subgroups the US, UK and Germany. All four suggest that the share of people living with NAFLD might be as high as three in eight. This is far too high a screening burden for the hepatology community to manage on its own. However, it should have broader implications for overall treatment pathways.
If the liver is the "canary in the (metabolic) coal mine," as Stephen Harrison frequently argues, then everyone in the metabolic disease cascade should be interested in screening patients to prevent the various metabolic diseases before they manifest as serious conditions.
The data sources include a German population study that was accepted for publication last week (Jörn Schattenberg, last co-author), the SUNN study that Wayne Eskridge has shared previously on this podcast, and data and insights from Ian Rowe's extensive study of the Leeds, UK population. Also, Louise Campbell discusses some raw data she has compiled from Tawazun work and Roger references the two studies that Stephen and colleagues conducted at the San Antonio Medical Military Center.
This conversation explores the need for and value of patient education in the NASH Patient Care process. It starts with almost a tangential request that some of the money budgeted for expensive systemic HCC therapies in the UK be rededicated to patient education earlier in the treatment process.
It starts with almost a tangential request that some of the money budgeted for expensive systemic HCC therapies in the UK be rededicated to patient education earlier in the treatment process. From there, the conversation shifts to consider the value of the need for early-stage treatment strategies in poorer countries that are never likely to be able to afford the expense of drugs or treatment modalities. In the end, each panelist describes a change she would like to see in the next 2-3 years.
This conversation explores the different challenges that liver nurses and advanced practitioners face when providing NASH patient education.
It starts with Stephen Harrison noting that this weeks' reported results from Madrigal's MAESTRO-NAFLD Phase 3 trial promises a day when we can reduce HCC and cirrhosis if we can counsel patients early enough in the process.
From there, the conversation shifts to consider the different specialties that can play a role, including not only hepatologists and nurses, but also podiatrists, bariatricians, endocrinologists and gynecologists. The rest of the conversation covers an array of prospective educational tools and the need for specific education that hits specific key points.
This conversation explores the different challenges that liver nurses and advanced practitioners face when providing NASH patient support.
It focuses on issues including health discrimination, the general challenges in deploying nursing care early in the disease progression and the mismatch of needs and resources. In the end, we learn about nurses who make their own recordings and encourage patients to create their own discussion groups in the medical office.
Episode 9 asks the question, "Are We Taking Full Advantage of the Skills and Knowledge that Liver Nurses and Advanced Nurse Practitioners Bring To NASH Patient Care and Education?"
In this conversation, we meet the four key nursing opinion leaders who have joined Louise Campbell and Stephen Harrison for the full episode. You will get to meet Kathryn Jack, Michelle Clayton, Pam O'Donoghue and Patrizia Kunzler and learn about the broad sets of skills and experiences each brings to this episode.
At the start of the episode, Stephen Harrison responds to a question that a patient e-mailed to SurfingNASH.com during the previous week.
Louise Campbell convenes liver nursing and nurse educator experts Kathryn Jack, Michele Clayton, Pam O'Donoghue and Patrizia Kunzler to consider where liver nurses and advanced nursing practitioners should fit into treatment and communication paradigms and what support they will need. Stephen Harrison joined to offer a different viewpoint.
Timestamps:
2:42 – Roger introduces session
4:07 – Louise starts discussion
5:37 – Stephen reviews patient case
12:10 – Panel introductions
22:33 – FIRST QUESTION: health discrimination and quality of care
24:58 – Michele: 2012-3 report stated that patients admitted with alcohol-related liver disease lacked HEP access, received poor treatment. We have made some progress but see similar issues today with COVID-19
27:59 – Patrizia: in Switzerland, liver patients come to care late in disease. Nurses provide excellent care but are not involved in prevention. Doctors drive the entire decision hierarchy
29:24 – Michele: Similar issue in UK; where nurses need decision input and greater investment in specialists, particularly in rural areas
31:47 – Kate: Agreed. We lose too many opportunities for nurses to inform and educate
32:40 – Pam: HCC patients on wards present "extremely unwell", in late stages. Nursing “short-staffed.” Not enough time to coach patients.
33:43 – Pam: I did recordings so I could work with one patient while another consumed recording. We also worked with patients in groups
36:06 – Stephen: We’re getting closer to our first NASH drug, which will reduce frequency of NASH-HCC if we can treat early enough in disease progression. Also, we need to create a communication model that combines nurses and doctors
37:33 – Stephen: Another target: podiatrists. They check patients' liver enzymes before Lamisil therapy, see dysfunction and don’t know what to do. And which other specialties? Obesity? Cardiology? ENDO? GYN? KEY: two “foundational pillars of education” - doctors and nurses - working collectively to develop and share content
39:38 – Pam: This requires trust between doctors and nurses. Trust takes time
41:24 – Kate: In prisons, once patients are diagnosed, we arrange conversations in person or video. Harder to build rapport without in person. With rapport, everything flows smoothly
43:15 – Kate: We have a system for GPs to refer patients for FibroScan, which is an excellent communication opportunity for nurses
44:58 – Michele: Some UK universities offer liver education, most do not. This is a global challenge
47:07 – Pam: We should invest some of this billions we spend on HCC systemic therapies in education before and early in disease progression
48:43 – Michele: Liver "blindsided" countries and planners who focused on renal, CV and cancer
49:34 – Louise: We spend heavily on expensive late-stage drugs but lack funds to locate and educate at-risk people early in process or steer them to clinical trials
50:39 – Louise: How can we use the Lancet Commission's competency documents better?
51:15 – Michele: Others have local competency documents in their own languages
53:25 – Patrizia: Not certain about Swiss association
54:15 – Stephen: Not aware of a common framework in US
57:48 – FINAL QUESTION: something you would like to see in next 2 years
58:46 – Michele: More global action from/for nurses
58:58 – Kate: Engage other specialties. New UK competency criteria around Fatty Liver
1:00:07 – Kate: More inclusive trial recruitment based on communication in patients' own languages
1:03:14 – Patrizia: Collaboration matters, but support/fund nurses today in research and publication
1:04:18 – Pam: Encourage British Liver Trust to be more aggressive; they can be quite effective
1:05:10 – Louise: Bring all the liver disease competencies we have to bear on NAFLD
1:06:53 - Business report
The Innovations in NAFLD Care 2022 Series includes a recent webinar and a hybrid meeting planned for Barcelona in May. This new event is a key new element in the effort to drive more holistic multi-specialty approaches toward diagnosis, treatment and management of patients with NAFLD and NASH. In this conversation, Stephen Harrison, Louise Campbell and Roger Green join Professors Schattenberg and Lazarus to consider innovative elements for this and future programs and to discuss the outcomes they would like this program (and others like it) to produce.
The Innovations in NAFLD Care 2022 Series includes a recent webinar and a hybrid meeting planned for Barcelona in May. This new event is a key new element in the effort to drive more holistic multi-specialty approaches toward diagnosis, treatment and management of patients with NAFLD and NASH. In this conversation, Stephen Harrison, Louise Campbell and Roger Green join Professors Schattenberg and Lazarus in discussing structural issues and social determinants of health that are shaping the growing Fatty Liver pandemic and why education is so important to combatting the pandemic.
The Innovations in NAFLD Care 2022 Series includes a recent webinar and a hybrid meeting planned for Barcelona in May. This new event is a key new element in the effort to drive more holistic multi-specialty approaches toward diagnosis, treatment and management of patients with NAFLD and NASH. In this conversation, Stephen Harrison, Louise Campbell and Roger Green join Professors Schattenberg and Lazarus in reviewing the program scope and agenda elements with an eye toward the most important ways to increase patient awareness of NAFLD and NASH.
The Innovations in NAFLD Care 2022 Series includes a recent webinar and a hybrid meeting planned for Barcelona in May. This new event is a key new element in the effort to drive more holistic multi-specialty approaches toward diagnosis, treatment and management of patients with NAFLD and NASH. In this 10-minute conversation, Professors Schattenberg and Lazarus outline the social and health system factors that motivated them to create this program.
Program co-chairs Jeff Lazarus and Jörn Schattenberg join the Surfers to discuss their "Innovations in NAFLD Care 2022" series and how it promotes the broader NAFLD Public Health Agenda.
This far-ranging discussion focuses on the Innovations in NAFLD Care 2022 webinar and event series with the goal of understanding what makes this series special and why it is so important today. The NAFLD Public Health Agenda is challenged with high prevalence levels, year-on-year double-digit increases in the number of newly-diagnosed cirrhosis patients, worsening of diets and exercise regimens brought about by the COVID-19 pandemic and an array of issues stemming from the lack of efficacious and tolerable medicines approved for this indication.
Roger Green assemblies audio clips from Surfing the NASH Tsunami's coverage of NASH-TAG 2022 to reveal an evolving view of the role combination therapies will play in treatment and management of NASH patients.
Discussion about "combination therapies" typically focuses on the idea of multiple agents prescribed concurrently to address a medical condition when monotherapy will not achieve desired goals. At NASH-TAG 2022, the concept of combination therapies took some interesting directions:
- Longitudinal drug combinations -- initial intervention designed to cause fast reversal of fibrosis or defatting of the liver, followed by a longer term therapy (mono or combination, but not with the first-round agent) designed to provide longer-term, more complete metabolic benefits in a regimen that is safer, more tolerable, less expensive, or some combination of these.
- Longitudinal diagnostics -- an early, inexpensive "rule out" test like FIB-4, followed by a liquid or machine based test that provides more accurate disease staging.
- Logical combinations -- so far, most drug combination trials have resulted from a manufacturer trying to resuscitate a developmental agent that missed endpoints in monotherapy trials. It would be more logical to design combinations based on complimentary modes of action.
This episode explores these and other combination therapy issues using quotes from the NASH-TAG 2022 coverage and Roger's commentary.
Global Liver Institute Founder and CEO Donna Cryer and Key Opinion Leader Professor Scott Friedman joined Roger Green at NASH-TAG 2022 for a far-reaching conversation on drug development and scientific advances in Fatty Liver disease.
This episode includes the entire discussion, plus a shorter one with Roger and SurfingNASH co-host Louise Campbell on some of the lessons emerging from NASH-TAG's first day.
Timestamps:
2:17 – Roger Green introduces the agenda for today’s episode
5:42 – Donna Cryer: “Favorite phrase” from the NASH-TAG Day 1 is “lessons learned”
7:02 – Scott Friedman on NASH-TAG Day 1: equal parts sobering and promising, with a major conceptual change
7:34 – Scott’s “sobering” points: highly anticipated clinical trials “did not pan out;” “we don’t know where this disease starts” or where to start treating it; and “we tend to approach the disease as one size fits all”
9:06 – Scott’s “promising” points: digital histopathologies, gene regulation and epigenetics, diagnostics, organoid technologies and more
11:33 – Roger: We need to think of “combination” treatment strategies not only as static same-time combinations but also sequencing of medications as replacements or add-ons
12:58 – Donna: To de-risks trials, include patients throughout objective setting and trial design
14:42 – Roger: Patient feedback may provide greater value to smaller companies with less margin for error
15:28 – Scott: Another consideration is patients’ disappointment "when things don’t work.”
16:20 – Donna: Patients realize the first drug “doesn’t have to be perfect”
17:13 – Donna: Interdisciplinary discussions at NASH-TAG are a very hopeful development
18:04 – Scott: We have a great deal to learn about underlying biology, but the efforts to do so make me hopeful
19:10 – Scott: Weight loss reverses a biology we can’t seem to accomplish with NASH drugs, which is promising
20:18 – Donna: We need multidisciplinary, multifaceted complete care approaches that do not rely on patients’ willpower and work for different types of patients
22:24 – Scott: “Personalizing” is not just about therapy, but also how the patient copes with the disease
23:02 – Donna: I remember early in my care being jealous of cancer patients for the holistic care they were able to receive that liver patients weren’t
25:55 – Donna: Will pruritis continue to be an ultra-rare indication when it exists with so many liver diseases?
26:25 – Scott: New, more elegant biologic definition of pruritis processes should lead companies to develop better therapies
28:59 – Donna: When they are approved, NASH drugs will be prescribed in as polypharmacy. Patients have multiple healthcare costs. I hope manufacturers will act responsibly
30:14 – Donna: Pricing for pruritis agents might inspire a backlash. Patient advocates will not support current pricing
31:01 – Roger: Keep in mind that modeling comes from finance departments and targets cash management and budgeting issues
31:34 – FINAL QUESTION: What do you believe will change and hope will change in the next year?
31:40 – Scott: Hope to see a drug trial result that will points to approval. Expect to see advances in NITs and digital histopathology
32:41 – Donna: Hope and expect two things: alignment between advocates, researchers, manufacturers and regulators on what mark we need to hit and what will happen once we hit it, and clarity around best use of NITs
33:31 – Roger: Expect to see adoption of digital histopathology in 23, maybe even end of next year. Hope to see widespread acceptance that stabilizing fibrosis is a perfectly acceptable clinical outcome for drugs
34:33 – Scott: We’ve known all along that FDA considers non-progression from advanced fibrosis to cirrhosis an acceptable endpoint
36:03 – Louise and Roger chat about fine points from NASH-TAG sessions and the first part of S3 E2
45:55 – Business Sect
Last weekend's NASH-TAG 2022 was the best attended event in the conference's six-year history, and probably the one that will have the greatest long-term impact on diagnosis, treatment and monitoring of Fatty Liver patients. In this wrap-up conversation, our seven-person panel (including two Pharma execs and one diagnostics entrepreneur) discusses strategies for improving cost-efficiency and patient participation in clinical trials.
As this conversation starts, Stephen returns to the "3 H&E" idea, mentioning that this will provide 60mm of tissue for review, instead of the current 20mm. Erin asks whether we should be looking at histopathology at all in view of the dismal (writer's word) balloon hepatocyte findings, but Stephen reminds the group that for studies that have already begun, they will have to use histology data as the core endpoint measure. Erin expresses the concern that various patients might look at the data and its challenges and question whether or not they even want to take the drug, but Louise and Stephen suggest that differ patients will react differently. The group kicks around more issues, concerns and possibly solutions around patient engagement and trial recruitment. In the end, the group expresses hope and expectation for what will have changed by NASH-TAG 2023. There is general hope and belief around having a positive set of Phase 3 results to review and some belief that digital histopathology will have made inroads in diagnostic algorithms and processes.
Last weekend's NASH-TAG 2022 was the best attended event in the conference's six-year history, and probably the one that will have the greatest long-term impact on diagnosis, treatment and monitoring of Fatty Liver patients. In this wrap-up conversation, our seven-person panel (including two Pharma execs and one diagnostics entrepreneur) considers how two key stakeholders -- FDA regulators and patients -- might respond to changes in clinical trial protocols that remove or de-emphasize biopsy-generated data.
This conversation is a continuation of 4.2, which focused on the NASH-TAG "fireside chats." This one starts with Erin Quirk's observation that events of the past year (presumably COVID-19 approvals) demonstrate that FDA is not slow to act when presented with clear need and high-quality data. Erin goes on to confirm that the statements FDA made during the fireside chat demonstrated a "real openness" to dialogue, which is what agencies do to signal that they consider it important to improve processes and/or solutions. Next, she suggests that a patient representative should be on future years' panels. FInally, she harkens back to Dr. Toerner's referral to HIV as a model for relatively fast, data driven change. The conversation shifts to focus on competing views on how to act in the patient's interest, with Erin, Ian and Amy all expressing points of view. Toward the end of the conversation, Roger shifts to discuss the practical implications of Stephen's suggestion that studies should review 3 H & E slides per patient instead of the current number (one) and the two of them discuss practical implications on screen fail rates and its flipside, patient acceptance rates in terms of study cost, timeliness and ability to standardize and simplify placebo response analyses.
Last weekend's NASH-TAG 2022 was the best attended event in the conference's six-year history, and probably the one that will have the greatest long-term impact on diagnosis, treatment and monitoring of Fatty Liver patients. In this wrap-up conversation, our seven-person panel (including two Pharma execs and one diagnostics entrepreneur) discusses reactions to the closing conference session: two one-hour "fireside chats" exploring the potential to improve clinical endpoints for non-cirrhotis Advanced NASH and NASH cirrhosis clinical trials.
This conversation focuses on the two "fireside chats" that served both as climax and denouement to NASH-TAG 2022. The first fireside chat started with a presentation from Stephen Harrison titled, "Non-cirrhotic Trial Endpoints-Is It Time to Pivot?" and proceeded to discuss proper clinical endpoints for Advanced NASH trials. The second chat started with a presentation from Vlad Ratziu titled, "Cirrhotic Trial Endpoints-Are We Ready for NITs?" and focused on different strategies for endorsing clinical trial endpoints for cirrhosis trials. The first question to group members was about how optimistic they felt coming out of that session and why. The three commercial panelists all rated themselves "5" on a six-point scale, while Ian, the academic, rated himself "4" or perhaps even "3." The commercial panelists focused on the value of having all key stakeholders, including FDA, in the same conversation and on the group's practical problem-solving approach. Ian based his lower score on practical problems he anticipated in developing data that would move the field ahead quickly and confidently. Stephen noted that while we will need to rely on histopathology in the short run, FDA signalled clearly that they are open to data and suggestion on how to use these data more consistently and reliably in pursuit of drug analysis. He suggested first that researchers come forward with guidelines recommendations consistent with what FDA requested and also descried the importance NAIL-NIT initiative in "breaking down the stovepipes" between companies to create a large, integrated data set for large, complex analyses.
Last weekend's NASH-TAG 2022 was the best attended event in the conference's six-year history, and probably the one that will have the greatest long-term impact on diagnosis, treatment and monitoring of Fatty Liver patients. In this wrap-up conversation, our seven-person panel (including two Pharma execs and one diagnostics entrepreneur) identifies what each participant considered the high-impact presentations of the conference.
This conversation is triggered by Roger Green's question, "What was the one thing about NASH-TAG that most surprised you." All group members mentioned the incredible passion and energy that fueled the meeting, but there were other, more specific mentions as well. Rachel Zayas mentioned a study presented at the meeting in which nine pathologists reviewed 80,000 cells looking for balloon hepatocytes. 1,138 of these cells (~1.5%) were identified by at least one pathologist as having a balloon hepatocyte, but only ONE (!) of these was identified by all nine. Clearly, this raises questions about whether the balloon hepatocyte is a robust enough metric to play such a pivotal role in steatosis scoring. Erin Quirk commented on a point Michael Charlton made during his presentation, that we neither control nor know enough about the dietary habits of respondents, even though a disparity between cells has the potential to confound results. From there, the group switched to discuss high-impact papers and concepts ranging from single cell transcriptomics to consider collagen control as a balance between reducing fibrosis and leaving sufficient collagen for hepatic self-repair. Toward the end of this discussion, two more ideas gained traction: Michael Charlton's focus on how to develop the optimal combination therapy and Erin Quirk's general observation on how gratifying it was to see big and small pharma working together.
SurfingNASH invited four attendees to the NASH-TAG wrap up (three first-timers, two corporate executives) to focus on presentations and discussion from the fireside chats. Highlights include:
4:20 – Introduction of first-time panelists Amy Articolo (Novo Nordisk), Erin Quirk (Terns Pharmaceuticals), Rachel Zayas (AGED Diagnostics) and the returning Ian Rowe (University of Leeds)
12:55 – Opening question: what about NASH-TAG 2022 surprised you most?13:04 – Consensus: energy and passion. Rachel mentioned the vast divergence in balloon hepatocyte readings
16:19 – Led by Stephen, group discusses powerful single slides22:51 – Question: What single presentation had a real impact on your thinking?
23:04 – Rachel: Single Cell Transcriptomics, which can identify disease drivers.
25:53 – Ian: Scott Friedman’s point about the need to balance blocking fibrosis with maintaining sufficient collagen for scar healing.
27:16 – Amy: Talks about upstream effects resonated because Novo Nordisk works to develop combination therapies.
28:53 – Erin: One “pleasant takeaway” was big companies sharing findings “shoulder to shoulder” with smaller ones.
30:04 – Roger: Rate reaction to fireside chats using 6-point scale. Erin, Amy, Rachel all say 5. Liked diverse viewpoints, high energy level. Ian says 4, maybe 3. Fears that following the path laid out in meeting will lengthen drug development.
36:06 – Stephen: We need to improve use of histopathology, design and implement a multi-year path to NITs as outcome drivers and develop NAIL-NIT, a multi-company, “agnostic” data repository to utilize everyone’s data to “ask the big questions” and drive large prospective trials. Also, we should provide analytics and perspective on unresolved issues that are delaying final FDA guidance document
47:02 – Amy: Key is to impact patients’ lives, which is more “function and feel,” less survival. We’ll look back on this as "The moment of change”
48:59 – Roger: FDA has becoming more open and encouraging since 01/21 webcast
50:33 – Roger: Stephen’s push to lower screen fail rates from 80% to 50% will drive 2.5x increase in eligible patients, thus shortening trials, reducing costs
52:35 – Stephen: This can also reduce placebo response rates, which are a major issue in interpretation
54:27 – Erin: Should we even be looking at liver tissue when pathologists are so mislaligned on balloon hepatocytes? Stephen: Eventually, perhaps not. But the ongoing trials today have to rely on histology55:02 – Erin: Are we creating medications that patients actually will want to take, given that many choose not to participate in trials? Louise: Decision is individual, but those who take time to make it wisely have the greatest prospects for success57:14 – Ian: Findings from trial populations and natural history populations can vary widely. Also, the NITs we use in trial need to work financially for the larger population
59:20 – Amy: Expanding trial population into primary care or OB/GYN would broaden target dramatically
1:01:02 – Question: something you hope to see that is different in a year and something you believe you will see1:01:14 – Louise: Patients and advocates at future Fireside chats
1:01:29 – Rachel: Tests that look separately at the different NAS elements instead of creating composite scoring
1:02:02 – Erin: A positive Phase 3 study result
1:02:31 – Amy: Solid and actionable programs to create solutions to issues identified this past weekend
1:03:03 – Ian: Expect positive Phase 3 data. Hope to see discussion around NITs that correlate consistently with histology and drive changes in outcomes
1:03:21 – Stephen: Hope to report positive Phase 3 trial
1:05:04 – Roger: Believe AI histopathology will play larger role; hope this entails more than simply emulating human brain
1:08:03 – Busines
SurfingNASH is covering each day of NASH-TAG 2022. This episode is a "morning after" conversation with Stephen Harrison, Louise Campbell and Jörn Schattenberg reviewing key points of the Day Two discussions, with particular focus on the two "fireside chats" that wrapped up the program.
Day Two of NASH-TAG included presentations of new data on wet markers, imaging and combination therapy, discussion of novel targets and advances in our understanding of basic science. All this led up to the meeting's climax + denouement: David Shapiro's talk on why the current trial and approval system is unsustainable and places unnecessary burden on patients, developers and investors, followed by two "fireside" chats that were, in fact, calls to action to rethink the appropriateness of clinical trial endpoints driven by so-called "semi-quantitative" histopathology reads driven by liver biopsy.
The day produced bold arguments, exceptional images, and some compelling new facts and perspectives. It was also long: Roger, Stephen and Louise started with a 6:15a MST SurfingNASH recording session and went through until the 8:15p MST program adjournment (for Louise in the UK, the cirrhosis fireside chat ended after 3:00a Sunday morning!) The next morning, the group met to review the speeches, slides and impassioned moments of a compelling, powerful day.
In the process, they revisited some of the day's high points, culminating in powerful statements on the problems with current clinical trial endpoints articulated by Stephen Harrison for non-cirrhotic trials and Vlad Ratziu for cirrhotic trials and supported by a powerful statement by Global Liver Institute Founder and CEO Donna Cryer focusing on how the current trial endpoint system places patients under undue burden and unnecessary, sometimes mortal, risk.
SurfingNASH is covering each day of NASH-TAG 2022. This episode includes two separate conversations, with Stephen Harrison, Louise Campbell, Mazen Noureddin and Quentin Anstee in the first and Donna Cryer and Scott Friedman in the second. Several common themes emerged in the two conversations, including the ideas that the future of NASH therapy lies in combination therapies and how impressive the field's advances in basic science are.
This episode includes two separate conversations. In the first, the group focuses on some of the specific presentations and topics covered on Friday: the emerging consensus that the future lies in combination therapies, the ways in which NIMBLE and LITMUS data (and differences between them) are instructive, and the dramatic advances in utilization of artificial intelligence. The second conversation included more patient perspective. It will take thousands of words to capture the depth of this episode in adequate detail and even then we couldn't do it justice.
In advance of NASH-TAG 2022 this weekend, Jörn Schattenberg joins the Surfers to answer a key conference question: are we ready to pivot toward non-invasive tests and better uses of histopathology? The group explores a range of questions and ideas that are likely to emerge during Saturday night's fireside chats.
The group explores a range of questions and ideas that are likely to emerge during Saturday night's fireside chats.
Highlights include:
7:03 – Stephen Harrison begins to discuss NASH-TAG 2022
7:45 – Jörn Schattenberg: we’re not ready to move beyond biopsy in 2022. Hope that we will bring forward the right program by end of year
8:31 – Roger agrees
8:43 – Stephen agrees, but looks to determine how to resolve pivotal challenges
9:46 – Stephen lists discussants for the fireside chats, including regulators, researchers and industry representatives
10:30 – Stephen lists key topics for his talk on non-cirrhotic trial endpoints
11:37 – Stephen lists “hurdles” biopsy "needs to overcome"
12:40 – Stephen’s key issue for histopathology : why we only score one H&E and one tri-chrome read per sample. He suggests three H & E and promises to reveal data on this in his talk.
15:08 – Jörn: "Why three?”
16:08 – Stephen: no magic, three non-contiguous reads “just makes sense.” The goal is to is to find ballooned hepatocytes or clustering, which might not appear in one slide but will frequently elsewhere in the sample.
18:11 – Stephen: choose the slide with the strongest presence of disease
18:47 – Key benefit: we screen fail fewer people on ballooned hepatocytes
19:59 – Potential secondary benefit: reducing resolution scores in the placebo group
21:09 – Stephen: three companies looking at this. All see a major difference.
21:29 – Stephen: there are commercial issues as well: high screen fail rates inflate costs and take lots of time. This approach will save money and time.
24:13 – Stephen: I like Jörn’s idea about using AI here. It will enhance reproducibility.
24:52 – Stephen: another issue is the shift from one to multiple pathologists. Multiple pathologists turns out to drive screen fail rate higher. We need something to counter that.
26:49 – Louise Campbell: getting more tissue is beneficial for the patient
27:52 – Louise: a lot of NIT evaluation comes from pairing to biopsy samples. The more samples, the more opportunity to test NITs.
29:14 – Stephen shifts to getting beyond the biopsy. FDA issue: link an NIT to outcome. The cirrhosis chat gives us our first shot on goal.
30:55 – Stephen: one challenge with non-cirrhotics is that NITs are not included in the major Phase 3 trials
32:07 – Jörn: this is a pivotal issue and NASH-TAG is the right place to discuss it
33:33 – Louise: consider quality-of-life as a high value outcome measure
33:57 – Jörn: how do we explore stabilization of disease with NITs?
34:31 – Stephen: all these are reasons to “set the stage” with cirrhotic cohorts first, learn the lessons, then extend to non-cirrhotics
37:56 – Closing question: what will make 2022 successful to you in terms of moving this agenda forward?
38:17 – Jörn: data from the consortia
38:50 – Stephen: a clear idea of what will get us to a surrogate endpoint with NITs. Until then. improve histopathology practices.
39:54 – Louise: anything with histopathology that leads us toward NITs is good. Also, we will need to do more remotely as long as COVID keeps rearing its head.
40:51 – Roger: let’s learn more and make two cases one on economics and the other on data quality
41:17 – Stephen: one more thing: better economics and stronger data will motivate Big Pharma to invest
43:53 – Stephen: at the end of the day, it’s all about economics
44:53 – Roger: burnt money feels wasted, makes study investment feel like an expense
46:09 – Stephen: listen for more Saturday night
47:16 – Business report
This conversation is part of SurfingNASH's 2021 NAFLD Year-In-Review. Andrew Scott, Global Policy Lead for the Global Liver Institute joins Louise Campbell and Roger Green to discuss the growing energy and impact of NASH patient advocacy.
This episode focuses on the steps that have increased reach and effectiveness of NASH patient advocacy dramatically in 2021. Andrew starts by noting some of the pivotal steps this year through which patient advocates began or expanded collaborations with the medical community in 2021, and then describing the activities that resulted from these collaborations: Global Liver Institute's (GLI) US NASH Action Plan, the range of guidelines and recommendations emerging from medical societies, the externally-led Patient-Focused Drug Development (PFDD) meeting with FDA, and a range of legislative initiatives in the US Congress and many states. Andrew notes that much of this activity emanated from decisions GLI took in 2017 to promote the importance of NASH in the constellation of liver diseases. Also, he notes the importance of discussing not only Fatty Liver disease but also the constellation of non-communicable metabolic conditions linked to it.
Today, GLI focuses on providing appropriate therapeutic options and support for every stage of NAFLD. Activities like the PFDD meeting focus on the need for drug development and approvals. Others, like GLI's collaboration in building and promoting a nutrition app, focus on earlier stage disease and helping patients live healthier lives before they experience disease. All activities address the needs to educate stakeholders and develop products to support, diagnosis, treatment and management at every stage of disease progression.
The conversation shifts to the need to conceptualize Fatty Liver in a broader context. Louise notes the statement that the liver is a mirror on the metabolism, or perhaps the patient. Andrew states that GLI will increasingly focus on the idea that LIVER HEALTH IS PUBLIC HEALTH and on overall wellness.
This leads Roger to wonder why other patient advocacy organizations silo patients so that the focus is on an individual disease as compared to overall patient wellness. Andrew observes that focusing narrowly on a single disease and serving as advocate for patients with that disease has been extremely effective for some patient advocacy groups in fund raising and public clout. However, Andrew notes, we are coming to a place in society where we need to view many of these issues in a more integrated way.
Louise observes from experiences in the UK that organizations competing for funds will not collaborate if they foresee an economic or PR downside. Andrew acknowledges this possibility, but reports that GLI has found success by collaborating with community liver groups to help them raise more money. This engenders good will and strengthens bonds within the community.
Roger shifts the conversation in the direction of metrics to point out that we do not yet have a concise, widely used and accepted test or metric to indicate success in slowing or stopping the growth in NASH. Andrew agrees and notes this is a particular challenge on Capitol Hill, where legislators are looking for hard numbers to demonstrate the need for (and later success of) programs. The GLI-supported NASH Care Act, which was initially entered in 2021 and will hopefully be passed this year, creates a Task Force charged with determining what the national metric(s) should be.
The next phase of this conversation reverted to broader issues around the liver as part of a holistic health system. Andrew's key points: (i) GLI recognizes that given the diverse levels and settings in which it operates, there is no viable "one size fits all" approach; and (ii) GLI is finding effective strategies for working more closely with government regulators.
Finally, Andrew's goal: To get a vote on the NASH Care Act sometime this year.
This conversation is part of SurfingNASH's 2021 NAFLD Year-In-Review. Professor Jeffrey Lazarus of ISGlobal and the University of Barcelona joins Louise Campbell and Roger Green to discuss the emerging NAFLD public health agenda.
Jeff Lazarus comes to the effort to create a global NAFLD Public Health agenda from his experiences spearheading similar efforts in HIV and Hepatitis C. The conversation begins with Jeff describing the path by which he shifted focus from each liver disease to the next. Just as reduction in HIV transition rates revealed the high level of Hepatitis C infections among HIV patients (particularly intravenous drug users), the reduction in Hepatitis C incidence following advent of the direct-acting antivirals revealed still-significant levels and growth rates of liver cirrhosis. This in turn revealed the degree to which NASH is driving the continuing growth of cirrhosis in the global population. It also revealed the degree to which efforts to reduce or eliminate NAFLD were lacking a strategy, an idea of the burden or sense of economic consequences.
From here, the discussion shifts to looking at similarities and differences between HIV and Fatty Liver Disease. One key similarity: a patient can have this disease for a long time before having to address it. A key difference: the steps one takes to combat infectious disease vs. what is more of a "lifestyle" disease.
Next, the group discussed Jeff's path to help shape a global consensus around the need to treat Fatty Liver and an action plan regarding how to do so. The first key was to determine how many countries are prepared to deal with NAFLD. Answer: out of 102 the group explored, none were prepared. This led to a two-year process with 218 global stakeholders to develop a global consensus statement on goals and actions, which we discussed on S2 E59. With these pieces in place, the global stakeholder group is working on a framework of sustainable development goals.
In response to a question from Louise regarding the impact of COVID-19 on these efforts, Jeff stated public leaders have not and will not educate the public on the impact of diet and exercise on the disease.. As a result, NAFLD Public Health advocates need to educate leaders on why public safety and nutritious diets are goals for fighting Fatty Liver.
NOTE: It emerges that the countries with the best public preparedness for NAFLD are those that take guidance from hepatologists.
In response to a question from Roger, Jeff suggested the attitude that bad health behavior is an individual right but paying the costs of the result disease is a social cost is not new. Specifically, he noted that this attitude is not different from what we see with tobacco or alcohol. He went on to discuss the importance of promoting public health, not only as a way to improve individual behaviors but also to create and focus advocates. Today, he states, we are failing both to diagnose the disease earlier and to invigorate providers, patients and social actors to behave in ways that reduce the rate and severity of what is in many ways a lifestyle disease.
A comment by Roger about the relationship between urgency and action leads Jeff to discuss the "terribly unsexy"attribution fraction, a statistical analysis that estimates the percentage of severe liver outcomes that are attributable to a specific disease (for example, NAFLD vs. Hep C.)
As the conversation closed, Jeff discussed his priorities for 2022: (i) to create and work with partnerships to take actions that give life and substance to the consensus recommendations; and (b) to create more consensus opportunities around the work of Wilton Park and possibly a similar meeting in the Americas.
This conversation is part of SurfingNASH's 2021 NAFLD Year-In-Review. Co-host Dr. Stephen Harrison joins Louise Campbell and Roger Green to review five key NASH themes that emerged in 2021, while simultaneously discussing the year for Surfing the NASH Tsunami.
It seems fitting that the first SurfingNASH event of 2022 should include Stephen, Louise and Roger. In this thoughtful, fast-moving conversation, Stephen identifies what he considers five key areas where the Fatty Liver community has progressed in the past year:
1. Call to action -- 2021 saw two separate, vitally important calls to action to share the scope of the upcoming NASH pandemic with the medical community at large and begin to create forums and processes to develop an agenda and care practices that would reach far beyond hepatolotgy all the way to primary care and other specialties that have historically had little to do with the liver. Jeff Lazarus work with colleagues at Wilton Park and in over 100 countries to evaluate the current status of NASH diagnosis, treatment and screening around the world and to being developing a public health agenda. At around the same time, a multidisciplinary panel of US opinion leaders organized by AGA published a general call to action and a specific Clinical Care Pathway, starting at diagnosis, that included multiple specialties and, for the first time, set out to define a way specialties can work together in identifying patients at risk, screening them for disease, and then treating as appropriate.
2. Natural History -- 2021 saw publication of two major papers on the natural history and progression of the disease. One paper produced by Stephen, Naim Alkhouri and a range of associates, evaluated a large group of seemingly healthy middle-aged men who receive treatment at the San Antonio Military Medical Center and mirrored a smaller study 10 years earlier. The two studies were fairly consistent in determining that slightly over one adult in three has demonstrable NAFLD and one in seven or eight has documentable NASH. The difference in the populations was that while approximately 2% of the 2011 sample exhibited F2 or F3 NASH, that number almost tripled ten years later. These papers and Dr. Arun Sanyal's work published later in the year in the New England Journal of Medicine indicated that we can project a steadily increasing trend line for cirrhosis cases, with growth in most major markets at 10-12% per year.
3. Drug Development --news here was mixed, although Stephen points out that we have learned from each failed trial. SurfingNASH discusses this topic frequently, so suffice it to say that as the year ends, three medications recruiting or conducting Phase III trials and several other exciting, innovative agents have already demonstrated some positive Phase II results.
4. Weight loss surgery -- Stephen feels that the SPLENDOR study, which we discussed recently on the podcast (S2 E60), merits notice because of what it suggests about the ability of dramatic weight loss to halt or reverse cirrhosis. There are drugs in development right now that appear capable of producing the same levels of weight loss shown with bariatric surgery, which provides hope that we can eventually stabilize and perhaps regress fibrosis levels in cirrhotic patients.
5. Non-invasive testing -- Several different modes of non-invasive testing have made progress during the year, ranging from liquid tests that received FDA approval and/or enhanced their commercialization capabilities to published research suggesting that MR Elastography (MRE) has compiled much of the data necessary to prove outcomes with greater clarity and confidence than biopsy. Stephen shared his belief that 2022 will be the year when academics, drug developers and regulators begin to align around a strategy to move beyond biopsy with deliberate speed.
None of these items are new, but the way Stephen organizes them is clearly worth a long listen.
The last half of December marks our annual NAFLD Year-in-Review. Episodes 62-64 each include ~20 minute segments of longer interviews with Stakeholders who have made a dent in Fatty Liver disease in 2021.
In this episode, Louise Campbell and Roger Green are joined by Stephen Harrison, Jeff Lazarus and Andrew Scott. Conversation topics vary widely, with Stephen describing on what he sees as the five key themes in his NAFLD 2021 Year-in-Review, Jeff focusing largely on the public health agenda and Andrew discussing the steps by which patient advocacy is becoming an increasing force in public and private Fatty Liver disease discussions. Each guest is a leader in his topic. Each brings intellect, insight, experience and energy to the topic and this interview. Each is worth a serious listen...
The conversation with Stephen also provides the three weekly episode co-hosts an opportunity to look back on the breakthrough year for Surfing the NASH Tsunami in 2021.
This vacation is posting after SurfingNASH.com shut down for a year-end break, so timestamps will be coming early the first week in January.
This conversation is part of SurfingNASH's 2021 NAFLD Year-In-Review. Professor Jörn Schattenberg of the University of Mainz joins Louise Campbell and Roger Green to discuss research and insights regarding NASH cost effectiveness studies and related issues of quality of life.
Jörn Schattenberg begins our discussion simply by reviewing some of the year's highlights. His "proof of momentum" statement is unique and dead-on at the same time: Fatty Liver topics were addressed in three New ENgland Journal of Medicine articles this year despite not having a new drug approval. When discussing the Liver International paper on which Jörn was first author (and Vlad Ratziu was the last author), he noted two key non-economic issues. First, countries tabulated and manage patient populations differently. Second, Jörn notes that most countries underdiagnose NASH and NAFLD and spend most of the money with end-stage disease. Roger and Louise both suggest that we might be able to save much of the late-stage money with better early diagnosis or, as Louise puts it, "early opportunity to stop something." Jörn expands on the point by noting that Fatty Liver is a mirror on the entire metabolic system, so early diagnosis of Fatty Liver has benefits far beyond impact on the liver end point. Louise continues to drive a spirited discussion about the importance of early diagnosis, at one point noting that her car gets a complete check-over but our bodies don't. As the conversation continues to cover a broad landscape, Jörn notes the well-documented links between fibrosis stage and quality of life and that the economic benefits of high quality of life are well known. Roger raises Alina Allen's suggestion of using AI to analyze Electronic Health Records, after which Jörn expresses his appreciation for the efficiency and data richness of this idea. The group continues to review different metrics (age, which is more common, dental care, which are less so). The conversation continues to move quickly, shifting from global screening to German medical studies teaching health and diet in public schools to the non-productive (perhaps even counter-productive?) budgeting practices of the NHS. In the end, the group comes back to Louise's fascinating vision of the body as an integrated system.
This conversation is part of SurfingNASH's 2021 NAFLD Year-In-Review. Professor Kenneth Cusi of the University of Florida joins Louise Campbell and Roger Green to discuss the NASH multidisciplinary initiative organized under the aegis of AGA the resulting paper of Clinical Care Pathways.
In 2021, Ken Cusi played an integral role in the NASH Multidisciplinary initiative fostered under the aegis of the American Gastroenterological Association (AGA) and leading to the paper "Clinical Care Pathway for the Risk Stratification and Management of Patients With Nonalcoholic Fatty Liver Disease," originally published in "Gastroenterology". This conversation begins with Ken mentioning some of the motivations and sources that led to the creation of the multidisciplinary group behind the Clinical Care Pathway paper and the earlier "Preparing for the NASH Epidemic: A Call to Action." Ken starts this conversation by discussing the momentum that is building around taking a disciplined, multidisciplinary approach to the emerging NASH pandemic. He cites recent US publications based on the NHANES database and work done in Europe by Jeff Lazarus and Wilton Park as being major driving forces. The discussion moves on to Ken's prediction that 2022 will be a "great year" based on new or updated guidelines from AASLD, AACE and the American Diabetes Association plus Phase 3 studies coming forward for semaglutide, lanifibranor and resmetirom. Louise Campbell notes that not only are medical groups collaborating, but in the UK, food companies have requested more robust food labeling guidelines from the government there. Ken goes on to predict "a convergence of awareness" around the clinical care pathway and using FIB-4 as a first stage test. He notes that ELF and ProC3 will become commercially available, which will augment testing capabilities and goes on to discuss some larger studies taking place to better define risk for different elements of the population. Louise Campbell asks what is likely to change over the next 2-3 years, at which point Ken discusses the increasing momentum he believes will lead to more testing, increased data generation and studies and a broader awareness of the role the liver plays in overall metabolic health. Roger asks how the new testing and patient vigilance will fit into an already overcrowded patient visit workload. Ken suggests that placing FIB-4 results and guidance on electronic medical records will increase primary care awareness and action by itself. This energy is offset somewhat by a lack of compensation for primary care and endocrinologists who identify patients with cirrhosis and also by the emotional exhaustion of treating patients through the COVID-19 pandemic. From here, the group goes on to discuss the processes through which screening and diagnosis are likely to become more widespread and treatment will become better integrated. In the end, Ken discusses the reasons he is highly optimistic about where the entire NASH field is heading in the years to come.
This conversation is part of SurfingNASH's 2021 NAFLD Year-In-Review. Professor Manal Abdelmalek of Duke University joins Louise Campbell and Roger Green to discuss the use of older drugs to treat cirrhosis patients today and her views on where NASH drug development is heading.
Manal begins by discussing the inherent tension between the research world, which reveals several promising modes of action and drugs in development but are unlikely to yield a first approval less than two years from now, compared to patient treatment, where people living with cirrhosis are looking for help today. Her talk focuses on the value of stabilization as a goal for cirrhotic patients being treated today and in part on the advances in basic disease knowledge and specific drug and diagnostic development will empower HCPs to prescribe the exact drug therapy that is right for the individual patient.
The last half of December marks our annual NAFLD Year-in-Review. Episodes 62-64 each include ~20 minute segments of longer interviews with Stakeholders who have made a dent in Fatty Liver disease in 2021. In this episode, Louise Campbell and Roger Green are joined by Manal Abdelmalek, Kenneth Cusi and Jörn Schattenberg.
Highlights:
3:26 – Manal Abdelmalek introduction and discussion: opportunities in the new drug pipeline and ways to treat using older agents until new agent arrive
5:06 – Manal: urgent to treat cirrhosis when it appears. Reversal may not be “achievable;” but blunting progression can provide stability
9:51 – We learn more about heterogeneity of cirrhosis patients all the time. Some day, genetics will pinpoint each patient's outcome to avoid so we can treat accordingly
12:20 – Louise: would a combined database of multiple cirrhosis drug study patients provide richer insights?
14:05 – Manal: let’s “shelf,” not "trash," drugs that had promising NIT results but missed in Phase 2b or 3 histology
18:57 – Louise: Manal does well to remind us how to use older drugs to stabilize cirrhosis patients.
21:05 – Manal: until new drugs become commercially available in 2-5 years, using older drugs better will be key
23:07 – Ken Cusi introduction and discussion: development of multi-disciplinary activities and clinical care pathways
24:10 – Ken: New data on prevalence and etiology of NASH cirrhosis spurred multi-specialty activities
24:41 – Key insight drivers: NHANES analyses, endorsements from medical societies and global journals, work of Jeff Lazarus and Wilton Park
27:01 – 2022 a “great year:" new/updated guidelines, major Phase 3 trials progressing
30:00 – Louise: AGA critical care pathway work and collaboration among specialties pivotal, positive and extending to related consumer industries
31:26 – Ken: 2-3 years from now, foresees “convergence of awareness” to expand FIB-4 and other simple tests to more patient risk subgroups.
33:25 – Study in progress: screening large number of patients to determine NASH prevalence among non-diabetic patients
35:34 – There was significant debate whether to include screening for T2D patients in the 2018 AASLD guideline recommendations
37:03 – Louise: Fatty Liver disease has far broader implications than simply for the liver
38:41 – Roger: asks how liver testing and vigilance will fit in schedules and practices of already overburdened providers
39:55 – Ken: requires a of simple, inexpensive, easily accessible Stage 1 tests like FIB-4, was key to its selection
42:22 – Jörn Schattenberg introduction and question: how are cost effectiveness analyses progression
44:25 – Jörn: 2021 has been “an exceptional year” for NASH
46:04 – Collaborated with Vlad Ratziu and others to produce cost of illness study published in Liver International in 2021
49:39 -Louise: why does it feel like we study cost effectiveness only for expensive new drugs and never measure cost effectiveness of inaction?
50:38 – Jörn: value of monitoring relies on measuring related risks from cardiovascular and other systems
52:22 – Roger: re Louise’s question, most cost effectiveness work evaluates a specific new expenditure, not a global “what if”
55:44 – Jörn: quality-of-life, which has clear economic costs, strongly associated with NAFLD
57:14 – Roger: Using HER to identify patients at risk might be a more palatable way to target education and information
59:50 – Jörn: An Optum database algorithm built by NIDDK provides a look at how to target
1:01:09 – Episode ends
This conversation is part of SurfingNASH's 2021 NAFLD Year-In-Review. Fatty Liver Foundation Founder and President Wayne Eskridge joins Louise Campbell and Roger Green to discuss the recently-completed SUNN study that was initiated and shepherded by FLF. Wayne discusses study results and the challenges for an orgganization like FLF in conducting this kind of study.
Wayne focuses intently on what the study tells us about prevalence of disease in the US. Like the San Antonio Military Medical Center research that Stephen Harrison et al. authored in 2011 and 2021, the study suggested a far higher rate of NAFLD and NASH than typical estimates project, with a NASH rate of 17% in the study population! He also discusses frustrations with the existing order and prior estimates that motivated him to champion the study and some specific issues in actually conducting, analyzing and publishing it. Finally, he discusses the far larger, more ambitious SUNN 2 study currently in the works.
This conversation is part of SurfingNASH's 2021 NAFLD Year-In-Review. Professor Alina Allen of the Mayo Clinic joins Louise Campbell and Roger Green to discuss the rapid progress the profession has made in improving user-friendliness and ease of interpretation of MRE and the coming expansion in the role that non-invasive liver testing will play in the years to come.
Alina notes some specific new information about MRE and other non-invasive testing methods that have come to light in the past year. Key new points about MRE include (1) Alina's statement that "we an actually diagnose NASH" using MRE and MRI-PDFF, (2) Alina's comment that we can execute MRE in a five-minute session, and (3) there are demonstrated correlations and precision prediction data for MRE and cirrhosis. The predictive power of MRE on likelihood of progression allows a way to match pairs in clinical trials more accurately by adding the act of pairing by active and control groups. Alina also notes that the same probability metrics that allow researchers to match pairs in a trial will also power the treating physician to schedule the next MRE in 1-5 years depending on relative risk of progression. In the end Alina suggests that we do not need MORE biomarkers, but instead we need to determine the best way to explore the ones that have been developed in the last few years.
If you listen closely, you will hear Alina discuss some questions that will be answered and data that will be presented at NASH-TAG 2022.
This conversation is part of SurfingNASH's 2021 NAFLD Year-In-Review. Dr. Mazen Noureddin, Director of the Fatty Liver Program at Cedars Sinai, Los Angeles, joins Louise Campbell and Roger Green to discuss advances in AI in histopathology.
Mazen Noureddin notes that while non-invasive tests are important and likely to become more so over time, drug development today will need to rely on AI to interpret and ultimately improve histology reads. One benefit he notes is the ability of AI reads to reveal differences between cirrhosis patients in terms of percentage of liver that is F4 vs. F3. In one study, AI also reduced the percent efficacy in a placebo group when compared to human readers. Mazen raises the pivotal question, "When are we going to use these AI techniques in clinical trials?" He and Louise Campbell suggest that we might have enough confidence today to analyze via AI, if only to compare results to what traditional, error-ridden approaches. He notes thats Louise suggests strongly that adopting the Ishak score might be a good way to go. Ultimately, Mazen suggests we can detect more liver features and also clarify unclear results.
The last half of December marks our annual NAFLD Year-in-Review. Episodes 62-64 each include ~20 minute segments of longer interviews with Stakeholders who have made a dent in Fatty Liver disease in 2021. In this episode, Louise Campbell and Roger Green are joined by Mazen Noureddin, Alina Allen, Wayne Eskridge.
Highlights:
7:51 – Mazen Noureddin begins talking about AI and histopathology by pointing to recent review papers listeners should read, one from Mayo Clinic and another from Mazen and colleagues.
8:21 – AI tools: machine learning and deep learning. Key AI targets: non-invasive testing and histology. More recent progress in histology.
10:09 – History of why histology in NASH has become increasingly controversial over time and how the challenge will grow. AI can address many of these controversies.
12:42 – Paper earlier this year: three expert pathologists working in tandem can strengthen reliability AND their results correlated with PathAI. AI also provided more granularity on specific disease levels within a cirrhotic liver and reduced placebo success rate.
17:10 – Louise: Should Intercept use AI methods in their re-read of 18-month biopsy data? Mazen: yes. We need a path to get regulators to accept AI this way.
19:40 – Louise: Why don’t we use Ishak instead of Metavir for cirrhosis coding? Mazen: another great question!
22:01 – Alina Allen begins
23:20 – In the past year, we have learned that not only is MRE the most accurate estimator of fibrosis, but we can diagnose now based on liver stiffness (LSM) + PDFF, all in an automated 5-minute process.
24:51 – Mayo CGH study (2021) proves we can correlate LSM today with five-year outcomes. Provides far better trial screening and matching data than simple biopsy.
27:07 – Roger: how can this change how we coach and advise patients?
29:04 – Alina: we can use LSMs today to inform patients better, improve their care and allocate use of expensive tests more properly.
30:55 – Roger: how does this fit into a Critical Care Pathways world. Alina: we can improve 1st-line granularity via AI analysis of patient’s medical history. If this filters more people out, it makes elastography or a blood-based biomarker more efficient, therefore more affordable,.
33:07 – Roger notes that sounds more like common commercial uses of AI than the AI-based histology reading we discussed with Mazen.
35:43 – Louise: if you had a magic wand, what model would you create to make MRE available when appropriate. Alina – first, teach people it is not too expensive or difficult, then create regional centers of excellence by putting software on existing MRI machines. Finally, educate patients and physicians.
38:10 – Alina: you do not need a full 45-minute MRI to get an MRE, but only a 5-10 minute process. thereby saving time and money.
41:03 – Wayne Eskridge begins
42:35 – Wayne: decision to start the SUNN study borne of dissatisfaction over recommended standard NOT to screen for NAFLD.
43:35 – Study pitch received unexpectedly positive reception from industry but learning about IRBs and trial management was a “real education.”
46:12 – Wayne: point of study was to go outside medical system to asymptomatic, uninformed people, in the belief they had underlying health concerns and would tbe motivated to learn.
47:48 – Louise: "Amazing" study identified potential clinical trials candidates. Why does SUNN show far higher levels of fibrosis than the other studies?
48:56 – Wayne: this is not a general population study, numbers probably are higher.
52:19 – Peak age of 40-50 is younger than with most studies; we know it progresses steadily. Message: we should be screening high-risk patients younger.
55:14 – Wayne: Hard cost was ~$120. Took 8 months to complete running heavy patient loads.
SPLENDOR lead author Ali Amirian, the Surfers and audience member Shardool Jain of Altrix Bio debate whether and when bariatric surgery might become first line therapy for multi-morbid metabolic patients.
Dr. Jain takes the position that for many patients with metabolic co-morbidities, drugs tends not to work over time, so why not go to bariatric earlier in therapy...even in first line? Panelists disagree to varying degrees. After Dr. Jain leaves, the group answers Roger's question about what they anticipate might be long-acting effects of this pivotal study.
A question from Ali Aminian leads the group to ponder whether cirrhosis can truly be regressed. The consensus is that many good things can happen (for example, fibrosis can be regressed) but that platelet levels never rebound.
From there, the panel considers the likely effect of the later-generation GLP-1s like semaglutide or tirzepatide, which report 10-15% overall weight loss, on MACE and MALO, as well as the in-development double and triple-agonists that report weight loss >20% in early studies.
The Surfers, joined by SPLENDOR lead author Ali Aminian, broaden their discussion into considering MACE and MALO patients into clinical trials.
After Roger Green notes that the percentage reductions in MACE (7.2%) and MALO (7.3%) were virtually identical, the group returns to explore the question of including co-morbid metabolic patients in clinical trials. To spur the discussion forward, Ali shares some additional insights on differences in how the bariatric surgery group performed in SPLENDOR vs. the group that did not receive surgery.
Lead author Ali Aminian shares key findings from SPLENDOR on the impact of bariatric surgery on Major Adverse Cardiovascular Events (MACE) and Major Adverse Liver Outcomes (MALO).
Top-line: over a ten-year followup period, bariatric surgery led to a fourfold decrease in MALO and almost a twofold decrease in MACE. This led Stephen Harrison to ask whether it makes sense to combine MACE and MALO as an endpoint in future studies and to comment on the oddity that most specialties seek to include patients with relevant co-morbidities in their clinical drug development trials but NASH drugs seek to exclude them.
Lead author Dr. Ali Aminian of the Cleveland Clinic joins the Surfers to discuss the recent SPLENDOR Study, which focuses on the effects of bariatric surgery on Major Adverse Cardiovascular Events (MACE) and Major Adverse Liver Outcomes (MALO).
Stephen Harrison and Roger Green are joined by Fatty Liver Foundation President Wayne Eskridge.
9:02 - Ali Aminian begins to discuss the SPLENDOR study
11:38 - Ali explains the dual study outcomes
13:31 - Wayne has the first comment, then Stephen asks about sub-populations. Ali notes that the small sample size of events limits the ability to do so.
16:25 - Stephen asks whether it will be a good idea to analyze for MACE and MALO together, rather than separately, and describes the large shift in trial enrollment thnking this might cause.
17:53 - Stephen asks whether study explored renal disease in a cardio-hepatic context. Ali discusses why not
20:20 - Roger notes virtually identical declines in MACE (7.3%) and MALO (7.2%), asks whether patients in the trial exhibited both
23:30 - Ali shares preliminary analyses (not ye released) about the impact of bariatric surgery on disease outcomes. (CAN'T MISS)
24:35 - Stephen notes that these numbers look similar to the placebo group in the cenicriviroc trial
26:19 - Ali comments that having 100 F4 patients does not provide much power for analysis. Stephen says it might be "25 times" what anyone else has.
28:51 - Ali asks Stephen whether he can envision new agents having the potential to drive regression in cirrhosis patients.
30:02 - Stephen describes a small, recently reported efruxiferman trial that appears to do so,
goes on to hypothesize that over time we will find a strategy
35:13 - Wayne worries whether "the siren song of surgery" will stop people from doing the hard behavioral work
35:59 - Ali: the problem is 40% obesity, 10% severe and until recently, no way to treat it. Expresses optimism and hope for semaglutide and the GLP-1s to come
38:10 - Roger asks how the coming double and triple agonists that report 20+% weight loss will compare to surgery in outcomes
38:49 - Ali: we need to do trials, but effect should be the same. Stephen agrees
40:31 - Shardool Jain, Director of R&D at Altrix Bio, joins from audience to ask if members can envision a time where bariatric surgery becomes first line therapy for extremely obese patients
42:40 - Ali suggests it may make sense for severely obese patients with multiple weight-related morbidities, not otherwise
44:50 - Stephen asserts we do not have enough surgeons in the US to execute the strategy. His preference: solve challenges that will reduce adherence with the new weight loss medicines
46:29 - Roger makes three points. 1 - surgery in cancer is not an early-stage strategy as Shardool suggests; 2 - from his own experience, diet and exercise can be exceptionally effective in the motivated patient; 3 - you get one shot at surgery, many at medication
47:31 - Diet conversation continues...
50:57 - Shardool and Stephen exit
51:04 - Ali addresses NIT issue by noting that when data for these first patients were generated in 2004, there were no practical NITs available
51:43 - Last question: the most powerful long lasting effects of SPLENDOR
52:03 - Ali: 1. Obesity is the main driver in Fatty Liver Disease. 2. Well populated, well-followed populations may provide unique insights
53:29 - Wayne: "the guidance that the heart-liver axis can be affected so dramatically is something we can use" with patients
54:12 - Roger: 1. Forecaster says investment in the double agonists and triple agonists becomes more attractive. 2. Advocate notes that weight loss can help patients all along the NASH spectrum
56:22 - Business section
NASH-TAG 2022 takes place in Deer Valley Utah and on-line from January 7-8, 2022. Join Surfing NASH to learn about the last three sessions of the meeting, which include multi-stakeholder "fireside chats" about how to make progress in non-invasive testing for non-cirrhotic NASH and NASH cirrhosis.
Co-chair Stephen Harrison leads the panel through key sessions from NASH-TAG. This conversation starts with a review of Session 7, which features presentations on PNPLA3 and HSD17B13 knockdowns and a range of novel targets. Discussion proceeds to Session 8, which includes presentations on several key basic science topics ranging from transcriptomics to integrin. Finally, Stephen leads the group through discussion of the two fireside chats, where collections of governmental, commercial and academic stakeholders discuss how to make progress in using novel tests for products designed to treat patients with non-cirrhotic NASH and, separately, NASH cirrhosis.
NASH-TAG 2022 takes place in Deer Valley Utah and on-line from January 7-8, 2022. Join Surfing NASH to learn about important updates from the three consortia (LITMUS, NIMBLE and the NIH Cirrhosis Network), "new news" in wet biomarkers and combination therapy and a stimulating session with PathAI and Histoindex covering artificial intelligence.
Co-chair Stephen Harrison leads the panel through key sessions from NASH-TAG. This conversation starts with a review of Session 4, in which Quentin Anstee presents updates from the LITMUS consortium, Arun Sanyal presents updates from NIMBUS, and Vijay Shah provides information about the NIH Cirrhosis Network. From there, Stephen reviews Session 5 with its focus on artificial intelligence leaders PathAI and Histoindex. The conversation concludes by reviewing the eclectic and intriguing Session 6, "What's New Out There and How To Interpret What It All Means," which has talks on the AASLD NASH Task Force, news on wet biomarkers and an update on combination therapy.
NASH-TAG 2022 takes place in Deer Valley Utah and on-line from January 7-8, 2022. Join Surfing NASH to learn about the important and innovative drug development and basic science talks in the meeting.
Co-chair Stephen Harrison leads the panel through each of the sessions during the conference's first morning. The session starts with Michael Charlton's annual "Year in Review" talk, includes discussions on an array of drug classes and ends with a session on the biologic basis of NASH progression. He pauses at the end of his review of each session, thus leaving Steering Committee member Jörn Schattenberg and Surfers Louise Campbell and Roger Green to comment on favorite presentations, ask questions and place this information in the context of what we are learning elsewhere about Fatty Liver disease and the drugs that are being developed to treat it.
NASH-TAG 2022 Co-chair Stephen Harrison and Steering Committee Member Jörn Schattenberg review the upcoming conference, focusing on major issues in NAFLD and NASH diagnosis, staging, treatment and monitoring.
NASH-TAG 2022 faculty, format and schedule suggest that this conference will produce breakthroughs in knowledge and consensus about NAFLD therapy. This week, NASH-TAG 2022 Steering Committee member Jörn Schattenberg joins the Surfers to discuss key presentations and critical issues in the conference. NASH-TAG co-chair Stephen Harrison walks the panel and audience through the entire NASH-TAG agenda, with Jörn, Louise Campbell and Roger Green contributing questions and comments throughout the session.
Highlights from the program:
8:54 – Stephen provides a little background on NASH-TAG
9:44 – Stephen begins to discuss Friday morning program
10:34 – Describing the first session, “A one-stop shop”
13:10 – Jörn Schattenberg comments on Session One
14:09 – Roger Green comments on Session One
15:10 – Louise Campbell comments on Session One
15:26 – Stephen discusses Sessions Two and Three, with comments on the oral presentations thrown in
18:24 – Louise comments specifically on the talk about why NASH-related HCC is resistant to treatment; Stephen agrees and amplifies
19:02 – Jörn comments on Sessions Two and Three
20:19 – Stephen discusses the break session and goes on to discuss Session Four
23:18 – Roger asks about which oral presentations will appear at the conference, Stephen demurs
23:55 – Jörn expresses enthusiasm that the LITMUS, NIMBLE and the NIH Cirrhosis Network
25:15 – Stephen discusses Session 5
26:43 – Roger expresses enthusiasm for the entire afternoon program (Sessions 4 and 5)
27:09 – Stephen discusses the scope and scale of the efforts LITMUS and NIMBLE are making, and goes on to discuss recent progress against cirrhosis in the context of mentioning the cirrhosis network
28:29 – Jörn expresses positive outlook on the Path AI and HistoIndex presentations
29:05 – Stephen begins review of Day Two, Session Six.
]31:14 – Stephen: “This may be one of the most intriguing sessions”
32:25 – Roger begins comments on Session Six
33:02 – Louise comments on Session Six
35:07 – Stephen begins review of Session Seven
36:24 – Louise begins comments on Session Seven
37:06 – Stephen begins discussion of the second evening with Session Seven
37:56 – Jörn comments on Session Seven
38:22 – Stephen discusses the last two hours of the meetings – “fireside chats” with governmental, corporate and academic stakeholders about whether it is time to pivot away from semi-quantitative biopsy-based endpoints toward NITs.
40:04 – Roger agrees with Stephen’s exceptional excitement about the potential of the fireside chats; Stephen elaborates on what will make the chats so special
42:23 – Final question: one more thing each panelist would like to point out in the agenda?
42:34 – Jörn praises “great program,” wonders whether the fireside chats should have included a patient representative
43:04 – Louise echoes Jörn’s comments on program quality and wish for a patient representative in the fireside chats
43:50 – Roger asks whether talks on the PNPLA3 and HSD17B13 knockdowns presage a longer-term future for therapies
44:42 – Stephen is partial to the fireside chats, expresses belief that researchers will take away from this meeting something they can use in research
454:52 – Business section
Lead author Jeffrey Lazarus and co-author Jörn Schattenberg join Stephen Harrison, Louise Campbell, and Roger Green to discuss the groundbreaking paper "Advancing the Global Health Agenda for NAFLD." This conversation starts with Roger discussing the recent Episode 49, in which Kenneth Cusi presented the multi-specialty clinical care pathway approach fostered by the American Gastroenterological Association in harmony with other specialties and Scott Friedman's comments in Episode 55 about NASH as an environmental disease caused by changes in global diets and their effect on the liver through the microbiome.
Jeff notes that he sees working in parallel with environmental and active lifestyle advocates as a cause for hope. The conversation shifts to the growth rates for cirrhosis in countries around the world and what that implies in terms of how fast the patient load will double or triple. This will cause increases in cost and worker demand nations are not prepared to address. The final question asks the group where panelists believe they can have the greatest impact, which leads to a follow-up question from Roger about whether stating aggressive incidence numbers might scare off payers, particularly private payers in the US. Jeff agrees this might be a risk as the session ends.
Lead author Jeffrey Lazarus and co-author Jörn Schattenberg join Stephen Harrison, Louise Campbell, and Roger Green to discuss the groundbreaking paper "Advancing the Global Health Agenda for NAFLD." This conversation focuses on what will happen now, why NAFLD is "the canary in the coal mine," and how we can combine strengths in different parts of the world to make all of our programs more robust.
For Jeff Lazarus, "what's next" includes a third, smaller Delphi study as well as a greater focus on Sustainable Development Goals (SDGs) around the environment and possible diet. As it continues, Stephen Harrison discusses ways to persuade patients (and perhaps societies?) to change habits, practices, and beliefs radically to fight this disease. Louise Campbell returns to the issue of SDGs to discuss how advocates can leverage the increasing volume of liver cancer patients to represent larger related issues, which leads Jeff Lazarus to comment on how prevalent and costly liver cancer is today, compared to other cancers. In the end, Stephen Harrison recommends a two-item impact strategy: clear messages supported richly through large, high-impact multimedia campaigns.
Lead author Jeffrey Lazarus and co-author Jörn Schattenberg join Stephen Harrison, Louise Campbell, and Roger Green to discuss the groundbreaking paper "Advancing the Global Health Agenda for NAFLD." This conversation centers largely on the issues of prevalence and cost data and the challenges of explaining the impact of NAFLD to non-stakeholders before Jeff ends with a remarkable anecdote.
This conversation kicks off with Stephen discussing the need for robust prevalence data. Jeff agrees but notes that past data in HIV and Hepatitis C have led to challenges and overconfidence after initial estimates were proven high. That said, Jeff notes that prevalence data will be key to accurately estimate the cost of what will be an extremely expensive disease in every world market. Louise amplifies Jeff's point on cost and Roger discusses the idea that NAFLD/NASH are different diseases at different fibrosis stages. Finally, Jeff tells a story about how all the Nature Reviews disease-specific journals coalesced around these recommendations in record time.
Lead author Jeffrey Lazarus and co-author Jörn Schattenberg join Stephen Harrison, Louise Campbell and Roger Green to discuss the groundbreaking paper "Advancing the Global Health Agenda for NAFLD." This conversation focuses on study methodology, what it felt like to participate, and the NAFLD Global Health Agenda from a physician's point of view.
In this conversation, Jeff describes the rigorous and ambitious process for conducting the study and analyzing results, Jörn describes what it meant to him to be part of the process, and Stephen Harrison takes a physician's perspective, noting how valuable this paper is and discussing how the way medical practice is structured in the US will make its implementation more challenging here.
Jeff also discusses some key findings and lessons, including the low level of preparedness across the globe to deal with the coming increase in cirrhosis cases and the World Health Organization's failure to recognize liver disease in some pivotal publications, while Stephen focuses on how patient practice visits are structured to achieve HEDIS scores but not necessarily help patients fully.
Lead author Jeffrey Lazarus joins the Surfers to discuss Advancing the Global Public Health Agenda for NAFLD, the major article recently published in Nature Reviews Gastroenterology and Hepatology. The article reports the results of a study with 218 Fatty Liver stakeholders in over 95 countries. Jörn Schattenberg, who participated in the entire exercise, joins Stephen Harrison, Louise Campbell and Roger Green to discuss the process, the insights and what comes next.
8:55 - Jeff Lazarus begins discussion by discussing Delphi process and scope
13:13 – Jeff reports: No country scored over 50 on preparedness for the NAFLD pandemic and goes on to list the eight core issue areas for this initiative
14:49 – Jörn Schattenberg discusses his reactions as a participant in the process
16:29 - Stephen Harrison says clinicians will support document, then goes on to describe how healthcare practices in the US militate against thoughtful patient care
18:45 – Stephen’s wish: more data so we can provide stronger insights on prevalence
19:55 – Jörn elaborates on how an agreed public health agenda and care models could streamline diagnostic and treatment processes
20:35 – Jeff: we are a long way from strong global data…and we need that data to demonstrate the current and future cost of disease to policymakers
22:22 – Stephen: we know enough today to target post-menopausal females with marginally controlled diabetes
23:25 – Louise Campbell sees various systems' weaknesses and strengths as source for planning
25:01 – Louise: “I can’t fathom” the potential cost savings of earlier screening and treatment
25:45 – Jeff discusses his Hepatitis C experience to say “This is how we start”
26:21 – Roger Green comments the dual awareness challenge: physicians do not think of NASH as even one disease when in fact it is two: a metabolic NCD in F2 vs. serious liver disease in F4
28:13 – Jeff describes the strong positive reaction of the Nature Reviews journals and others toward this paper
29:15 – Jörn: this kind of awareness will help us raise public and not-for-profit funding for related research initiatives
29:50 – Discussion shifts to “What comes next?”
30:01 – Jeff discusses ways the collaboration continues and notes that the liver community needs allies to make this happen
34:36 – Stephen: we need one messages to motivate patients to improve behavior and another to compel governments to spend
36:07 – Jeff: we need governmental structures to support individual activities
36:20 – Louise: we need to increase education and focus on small behavioral steps people can achieve
40:11 – Stephen’s key place for impact: a simple global message for frontline providers that looks forward to when NITs become accepted and drugs are available
42:44 – Roger asks how this effort relates to the US multi-specialty Clinical Care Pathways initiative
44:06 – Jeff: Clinical Care Pathways excellent, but we still need to focus on national health systems, sedentary lifestyle and patient education
45:37 – Jeff: Center for Disease Analysis forecasts a 2x – 4x growth in NASH cirrhosis between now and 2030 in the countries they have modeled
46:12 – Louise doubts our health systems can handle that kind of growth
47:48 – Jeff: cirrhosis will “sneak up” on global health authorities
49:49 – Final question: one place we can have impact quickly
50:02 – Jörn: working with policy makers in Germany to develop a national strategy
50:26 – Louise: educating policy makers in the UK
51:18 – Roger: develop a message that conveys the "two disease" idea
52:05 – Jeff: longer term modeling to demonstrate scale of problem
53:10 – Roger asks, if incidence estimates are too high, will anticipated costs scare off US and other payers
54:11 – Jeff sees overestimation as a potential problem
56:03 – Business section
This episode follows S2 E43 in discussing the possible role of NASH cirrhosis clinical trials in the transition from biopsy as gold standard to a post-biopsy world. Terns Pharma CEO Sen Sundaram joins this conversation from the audience to ask whether the term "cirrhosis" is medically helpful or might warrant replacement with "end stage liver disease." After vigorous discussion on this point, Sen departs and Stephen Harrison leads the group through a review of four ongoing NASH cirrhosis trials. The discussion veers into the issue of which analytics methods designers are specifying and why. At one point, Naim Alkhouri, frequent guest and principal investigator on the Gilead combination agent trial before the session ends. His specific contribution: MRE was not included in the Gilead trial largely for cost reasons.
The most striking fact to emerge from this conversation relates to the "beyond the biopsy" question. MRE is emerging as a highly reliable NIT that appears to produce reliable results regardless of mode of action and is generating correlations and ratios to fibrosis level decreases and other key metrics, yet it is not included in the designs of any ongoing NASH cirrhosis trial. Stephen describes this as the "stovepiping" of data. Companies consider the data they need, not ways it can be aggregated with other trials to solve larger issues. This issue bears further exploration in later episodes.
This episode follows S2 E43 in discussing the possible role of NASH cirrhosis clinical trials in the transition from biopsy as gold standard to a post-biopsy world. Stephen Harrison starts this conversation by reviewing a post hoc analysis of Phase 2 belapectin data from Galectin Therapeutics, followed by a review of the FALCON 2 stud of pegbelfermin in NASH cirrhosis, sponsored by Bristol Myers Squibb. Jörn Schattenberg, Mazen Noureddin and Roger Green add their perspectives to the conversation.
Stephen's primary point from the belapectin post hoc analysis is a practical one: the high correlation between an AST:ALT ratio>1 and HVPG levels can help clinicians suspect which patients have cirrhosis and possibly define candidates for NASH cirrhosis clinical trials. Mazen states that given the lack of trial data in this area, any secondary data that can be interpreted or integrated into a broader analysis is exceptionally helpful. Stephen asks what the ideal design would be for a NASH cirrhosis trial starting today. While answers vary, they all rely heavily on non-invasive tests to provide richness to the data and possibly set a foundation to become primary endpoints over time. This leads Roger to observe how much more complex and disease-focused trial design discussions have become over just the past two or three years.
This episode follows S2 E43 in discussing the possible role of NASH cirrhosis clinical trials in the transition from biopsy as gold standard to a post-biopsy world. Stephen Harrison starts this conversation by discussing why we focus on NASH cirrhosis and goes on to review the recent presentation of results from the REVERSE study on obeticholic acid. Jörn Schattenberg and Mazen Noureddin add their perspectives to the conversation.
In this conversation, Stephen starts by pointing out that non-cirrhotic NASH trials and NASH cirrhosis trials differ significantly in goals, endpoints and patient severity. From there, he dives into the NASH cirrhosis trial group with his review of REVERSE, which Vlad Ratziu presented at AASLD. Jörn Schattenberg and Mazen Noureddin also comment on design of this trial. Conversation focuses on two issues: who is the optimal patient for a NASH cirrhosis trial and what is the most appropriate attainable endpoint and, therefore, clinical design? On the optimal patient issue, the group agrees the ideal patient is a well-compensated cirrhotic, because the presence of portal hypertension makes the entire healing issue so much more complex. There was less agreement on the optimal design question.
Manal Abdelmalek, Jörn Schattenberg and Ian Rowe join regulars Stephen Harrison, Louise Campbell and Roger Green to recap NAFLD and NASH-related insights from the 2021 , the AASLD annual liver meeting. This conversation focuses on complexities and challenges NAFLD drug development and patient treatment will face in the future and ends with predictions about the biggest stories of the 2022 Liver Meeting (hopefully hybrid instead of only digital!).
The specific complications include microbiome, which has the potential to add a regional (or even individual) component to our understanding of NAFLD. Stephen Harrison speculates on how the scarcity of MRE machines will affect patient diagnosis if MRE becomes the dominant method for diagnosing/staging NASH and Roger Green notes that the advances in disease analytics and modeling have all resulted from continuing improvements in the quality and cost effectiveness of generating and analyzing data. Finally, panelists state when they expect to be the big story of the 2022 TLM, with the group divided evenly between those looking to Phase 3 results from ongoing trials and those who believe that the increasing presence of the patient viewpoint will drive significant changes in every element of how we diagnose, stage and treat patients in the future.
Manal Abdelmalek, Jörn Schattenberg and Ian Rowe join regulars Stephen Harrison, Louise Campbell and Roger Green to recap NAFLD and NASH-related insights from the 2021 TLMdX, the AASLD annual liver meeting. This conversation focuses how to make NITs the "gold standard" of drug development instead of biopsy.
The guests is Antaros Medical Chief Scientific Officer and recent SurfingNASH (S2 E50) panelist Lars Johansson, who joins the discussion from the audience to ask about use of spleen volume as a surrogate measure in F2 and F3, the value using AI models to re-evaluate old imaging data and the universality of the emerging NITs. Stephen Harrison praises the concept of going back into old imaging studies while Jörn Schattenberg cautions not to make the task of getting a drug improved even more challenges by bringing other organ systems into the core analysis. After Lars leaves, Manal Abdelmalek identifies genomics as another key item in the TLMdX agenda and Louise Campbell, who mentioned genomics in her "big dent in Fatty Liver" response, identifies three papers from the conference that collectively make compelling points about why and how genomics will shape the future of NASH drug development and, in special situations, patient treatment.
Manal Abdelmalek, Jörn Schattenberg and Ian Rowe join regulars Stephen Harrison, Louise Campbell and Roger Green to recap NAFLD and NASH-related insights from the 2021 TLMdX, the AASLD annual liver meeting. This conversation focuses on crafting the most robust efficient pathway to shift the gold standard of drug development from semi-quantitative biopsy reads to intelligent use on non-invasive techniques.
Opinions diverge about everything from how easy it will be to replace biopsy to exactly what that pathway might look like. What is clear is that everyone in this discussion believes with a hot passion that biopsy is a critical impediment to getting drugs approved.
Manal Abdelmalek, Jörn Schattenberg and Ian Rowe join regulars Stephen Harrison, Louise Campbell and Roger Green to recap NAFLD and NASH-related insights from the 2021 TLMdX, the AASLD annual liver meeting. This conversation focuses on what we have learned about NITs and clinical development testing that will, in the words of Stephen Harrison, "put a big, fat dent in Fatty Liver disease."
The conversation starts with the group congratulating Manal Abdelmalek on her wrap-up NAFLD talk at the 2021 TLMdX. From there, the group focuses on the shortcomings of using biopsy as the clinical trial gold standard and how strategic clinical trial design and interpretation of existing NIT data can build a bridge from biopsy through MRE/biopsy correlations to a total NIT future.
Manal Abdelmalek, Jörn Schattenberg and Ian Rowe join regulars Stephen Harrison, Louise Campbell and Roger Green to recap this week's just-concluded TLMdX 2021, the AASLD annual liver meeting.
When AASLD announced that the 2021 TLMdX would be held as a purely virtual meeting, attendees and observers feared a loss of focus and the kind of amplifying energy that comes from being with colleagues. That did not happen. Instead, the breadth, quality and novelty of the meeting's presentations generated exceptional positive energy despite the virtual setting.
4:10 - Roger starts by saluting Manal for giving the NAFLD Wrap-up Talk at TLMdX 2021, then introduces other panelists
6:58 - Icebreaker question: Where did this meeting "make the biggest dent" in Fatty Liver disease?
12:21 - Manal discusses how she organized and prepared for talk and describes "somewhat surreal" feeling of seeing semi-quantitative histology fail in trials where so many non-invasive markers suggested proof of efficacy
16:13 - Jörn points out the inherent tension between needed accelerated endpoints and being tied to a severely flawed "gold standard" of biopsy
17:15 - Stephen's simplest solution: capitalize on existing study results to link MRE, fibrosis and outcomes
18:56 - Manal counters: this assumes biopsy is the gold standard, when we know it is seriously flawed
21:02 - Stephen: it's time to "reach a common ground on what it takes to achieve replacement of histology with an NIT"
24:02 - Ian suggests that the FALCON trial history will strengthen FDA's attachment to biopsy
26:13 - Stephen's key to moving beyond biopsy: strengthening the data that supports credibility of NITs
28:13 - Jörn: having a combination of NITs that each reflect different elements of the disease makes effort easier and more credible
28:45 - Ian: controlled cirrhosis studies might allow quick validation and acceptance
29:35 - Manal: we know how to design better trials now, cites story of ALPINE 2/3 as proof
32:17 - Stephen: the path to the data-driven future explodes when the first drug is approved
33:32 - Lars Johansson (Antaros Medical) joins from audience to ask Stephen whether we can reanalyze spleen volumes from old trials and reanalyze imaging data possibly with AI
34:52 - Stephen salutes Lars's "very good insight" about the potential to reanalyze the "huge" bodies of data from older trials
35:54 - Jörn agrees, but cautions that we need to keep primary focus on getting a drug approved
38:41 - Lars returns to audience
39:25 - Manal returns to Louise's thought that one thing coming from meeting has to do with genomics, citing Million Veteran database
40:16 - Manal describes how single cell RNA data will shape the future of diagnostics and treatment in Fatty Liver diseases
41:10 - Louise refers back to various talks involving the patient-treatment impact of genomics and others implicating genetics as a possible reason for high variability in placebo response between trials.
43:42 - Stephen raises the diversity inherent in microbiome data as playing a role in making Fatty Liver so complex to characterize and treat
45:10 - Jörn points out that any drug that can "elevate above all these thresholds" and complexities will have to be "quite robust"
46:23 - Stephen envisions the day when drugs are approved based on MRE and the scarcity of MREs around the world creates a new set of challenges
47:37 - Manal observes that "precision medicine has been hot and heavy," which spurs Roger to note that all the key advances mentioned in the meeting are tied to advances in computing and modeling power
48:12 - Closing question: The biggest story a year from now? Stephen, Manal and Ian focus on "Phase 3 results." Jörn, Louise and Roger focus on ways patient empowerment will focus attention on better patient solutions.
57:05 - Business section
Drs. Michael Charlton and Mazen Noureddin and Global Liver Institute Director of Global NASH Programs Jeff McIntyre join Dr. Stephen Harrison, Louise Campbell and Roger Green to review some of the most important and exciting presentations from the final two days of the 2021 TLMdX, the annual meeting of AASLD.
Each panelist chose 1-2 presentations or posters from the 2021 TLMdX from AASLD that they thought conveyed a major topic or question in the meeting. The group discussed each paper, sometimes moving far afield the original topic. As usual with SurfingNASH, conversations were interspersed with challenging insights and comments, debate and laugher.More additional info about this episode?
Highlights include:
3:31 - Introducing tonight's panelists
17:51 - Michael Charlton and Mazen Noureddin kick off reconsideration of "Efficacy and Safety of Pegbelfermin in Patient with NASH and Stage 3 Fibrosis: Results from the Phase 2b FALCON 1 study" (Late Breaker 1.) Group discussion ensues throughout this section
35:21 - Mazen discusses "PROXYMO Demonstrates Safety and Efficacy of Cotadutide, a novel Incretin Co-Agonist in Biopsy-Proven Non-Cirrhotic NASH with Fibrosis" (Late-Breaker 1)
43:09 - Group discussion
48:36 - Stephen Harrison discusses "Vonafexor, a FXR Agonist, Induced Hepatic and Renal Improvement in the Randomized, Double-Blind, Placebo-Controlled LIVIFY NASH Trial" (Late-Breaker 1)
55:36 - Group discussion
1:03:12 - Louise Campbell discusses "Impact of Modest Weight Reduction on Serum Markers, Liver Histology and Disease Progression in Patients with Advanced Fibrosis Due To Nonalcoholic Steatohepatitis (NASH)" (Parallel 29)
1:09:12 - Group Discussion
1:15:13 - Louise Summarizes "The Fibrosis-4 Index and Severe Liver Disease Outcomes in Primary Care: a Stratified Cox Analysis" (Parallel 29)
1:20:29 - Group discussion
1:21:59 - Michael discusses "ARO-HSD, an Investigational RNAi Therapeutic, Demonstrates Reduction in ALT and Hepatic HSD17B13 mRNA and Protein in Patients With NASH or Suspected NASH" (LP11)
1:26:23 - Group Discussion
1:28:16 - Jeff McIntyre discusses "Lifestyle Management of NAFLD with Obesity" (Emerging Trends Symposium, "Tailoring NASH Therapy"
1:39:11 - Group discussion
1:46:08 - Final question: "What's the one thing that you hope that the part of the community that you touch most directly is going to take out of this meeting?"
Profs. Scott Friedman and Michelle Long, Dr. Naim Alkhouri and Global Liver Institute DIrector of Global NASH Programs Jeff McIntyre join Louise Campbell and Roger Green to review some of the most important and exciting presentations from the first three days of the 2021 TLMdX, the annual meeting from AASLD.
Description: Each panelist chose 1-2 presentations or posters from the 2021 TLMdX from AASLD that they thought conveyed a major topic or question in the meeting. The group discussed each paper, sometimes moving far afield the original topic. As usual with SurfingNASH, conversations were interspersed with challenging insights and comments, debate and laugher.
Highlights include:
5:27 - Introducing tonight's panelists
15:27 - Naim Alkhouri discusses "The Prevalence of Alcoholic and Nonalcoholic Fatty Liver Disease in Adolescents and Young Adults in the US" (Parallel 5)
20:33 - Group discussion
28:56 - Louise Campbell discusses "An advanced practice provider (APP) pathway achieves more effective weight loss in NAFLD patients compared to standards of care" (Parallel 2)
37:40 - Group discussion
46:28 - Scott Friedman discusses "The influence of host genetics on liver microbiome composition in patients with NAFLD" (Poster #`1654)
48:39 - Scott transitions to "The influence of host genetics on liver microbiome composition in patients with NAFLD" (Poster #1781)
50:31 - Scott ties these two results together in addressing the importance and complexity of microbiome: "I say that ...in part based on the work of Marty Blazer...an infectious disease doctor, who's sort of convinced me that epidemiologically it's very hard to explain how a disease showed up on our radar screens in a 20 to 30 year period, uh, that didn't exist before...Certainly our genes haven't changed over hundreds, if not thousands of years, to any extent. And so something external has changed. It comes back to the environment," and dietary changes.
52:53 - Group discussion
58:48 - Michelle Long discusses "Longitudinal association between MRE and liver-related events and CV events in NAFLD" (Sunday Presidential Plenary session)
1:07:56 - Group discussion
1:09:08 - Group discussion shifts toward the question of whether and when FDA might move away from biopsy as the requisite endpoint in drug trials
1:15:03 - Roger shares audience question on probiotics and NAFLD. Scott provides primary answer
1:16:37 - Jeff discusses Donna Cryer's talk on "Grit, Grace, Gratitutde and Resilience: What You Wish Your Doctors Knew about You" (Sunday Patient Forum)
1:22:53 - Group discussion starts by considering the best word to describe the optimal provider:patient interaction ("partnership" emerges as preferred choice)
1:28:23 - Roger discusses "Topline Results from the Alpine 2/3 Study," a Phase 2b trial evaluating 3 doses of the FGF19 Analogue Aldafermin,(Sunday Presidential Plenary session) and "Efficacy and Safety of Pegbelfermin in Patient with NASH and Stage 3 Fibrosis: Results from the Phase 2b FALCON 1 study." He connects these results by saying "What was striking is that if all you were doing was scoring the balls and strikes, then you'd say that those were both the same thing because neither one of them was going to point to a commercial success in launch." However, he continues, "the differences between the two vastly outweigh the similarities" in that pegbelfermin demonstrated minimal ability to differentiate from placebo while aldafermin clearly differentiated from placebo but might not have presented a strong enough commercial profile given other drugs in development.
1:33:07 - Group discussion
1:36:25 - Scott adds one comment on the importance of digital pathology if we are to continue relying on biopsy.
1:37:04 - Final question: "What's the one thing that you hope that the part of the community that you touch most directly is going to take out of this meeting?"
Global Liver Institute Founder, President and CEO Donna Cryer and her fellow patient and patient advocate Terri Milton join Stephen Harrison, Louise Campbell and Roger Green to discuss the ground-breaking NASH Patient-Focused Drug Development meeting held on November 4, 2021 and the advocates' priorities -- both those who spoke in the PFDD session and others like our panelists -- for changes in regulatory policy and programs.
In this conversation, the Surfers and the patient/patient advocate guests share divergent opinions about relative value of drug development vs. support for non-invasive testing as the top advocacy priority. The group wraps up the episode (and this conversation) by discussing the one message each person hopes regulators took from the Patient-Focused Drug Development meeting.
Global Liver Institute Founder, President and CEO Donna Cryer and her fellow patient and patient advocate Terri Milton join Stephen Harrison, Louise Campbell and Roger Green to discuss the ground-breaking NASH Patient-Focused Drug Development meeting held on November 4, 2021 and the advocates' perspectives that individuals brought to the meeting.
In this conversation, Global Liver Institute Founder, President and CEO Donna Cryer describes the history of the basic Patient-Focussed Drug Development concept and this particular Fatty Liver event. Patient and patient advocate Terri Milton discusses the message she hoped regulators would take away from this session and why she believes the group may have succeeded. Finally, the group discusses why regulators and advocates vary so greatly in terms of how they view the efficacy:safety tradeoff for first-in-class drugs.
Global Liver Institute Founder, President and CEO Donna Cryer and her fellow patient and patient advocate Terri Milton join Stephen Harrison, Louise Campbell and Roger Green to discuss the ground-breaking NASH Patient-Focused Drug Development meeting held on November 4, 2021 and some personal experiences that made PFDD such a priority.
In this conversation, patient and patient advocate Terri Milton shares her 20-year experience with NASH, cirrhosis, HCC (hepatocellular carcinoma) and how related effects like hepatic encephalopathy and the issue of waiting for a liver transplant affect her life. Stephen Harrison laments that he was not Terri's physician and describes the phenomenon of "peak and shriek" when a surgeon opens a patient's midsection and finds previously unknown evidence of cirrhosis. Finally, Louise Campbell discusses the story of Keiron Dyer, a former English national team player currently awaiting a liver transplant for primary sclerosing cholangitis.
Jörn Schattenberg and Mazen Noureddin join the Surfers to discuss five recently-reported or ongoing clinical trials in NASH cirrhosis. The reviews focus on study findings and their implications, but also on the methods used to conduct each trial and the implications of these designs on generalized learning and ability to move beyond the biopsy.
Stephen Harrison leads the group in discussing recent results from NASH cirrhosis trials, including the REVERSE trial with obeticholic acid, the FALCON 2 trial with pegbelfermin and a post-hoc analysis of Galectin Therapeutics' Phase 2 trial for belapectin. The group also discussed ongoing trials including the FGF-21 efruxifermin, the FGF-19 aldafermin, the Galectin-3 inhibitor belapectin and the combination agent trial from Gilead Sciences. Along the way, Terns Pharma CEO Sen Sundaram joins from the audience to ask whether the name "cirrhosis" is the most appropriate way to define the disease, given all that we are learning. This session takes a deep look at cirrhosis, with focus on clinical trials, disease pathology and patient management.
Global Liver Institute Founder, President and CEO Donna Cryer and her fellow patient and patient advocate Terri Milton join Stephen Harrison, Louise Campbell and Roger Green to review the ground-breaking NASH Patient-Focused Drug Development meeting held on November 4, 2021.
This patient-focused drug development meeting could be viewed as the culmination of seven years of effort by Global Liver Institute to encourage regulators and other stakeholders to think differently about NASH. In this episode, one post-transplant patient (Donna) and another patient living with disease while awaiting a transplant (Terri) share the comments and perspectives they brought to the November 4 patient-focused drug development meeting, while Stephen, Louise and Roger share their own points of view, which vary somewhat from the patients and each other. This is less scientific than the typical SurfingNASH session, but far more important in reminding all of us who we are here to help and what their goals for therapy are.
Highlights include:
2:51 – Roger Green introduces patient and patient advocate Terri Milton
3:11 – Terri tells her 20-year story of living with NAFLD, NASH, cirrhosis, HCC and other related health challenges
6:23 – Roger comments on “Dr. Google” and Stephen Harrison discusses Terri’s treatment history
8:19 – Terri finishes her story by discussing her own accountability for her health going forward and shares “one fact you wouldn’t know”
12:29 – Icebreakers from the panelists start with Louise Campbell discussing a high-profile UK athlete needing a liver transplant at a young age due to PSC
20:38 – Donna Cryer kicks off by discussing the history of Patient-Focused Drug Development
22:10 - The inception of Global Liver Institute and its work on policy in regulatory science for liver disease
24: 50 – Co-development of Patient-Focused Drug Development meeting under the aegis of GLI in collaboration with FDA
27:19 – Terri describes the messages she hoped to deliver to FDA, those she has delivered to researchers and her favorite moment of the NASH Patient-Focused Drug Development event
29:17 – Donna describes the pivotal points FDA officials experienced in the NASH Patient-Focused Drug Development meeting
30:08 – Roger’s surprise that FDA has not learned that patients value stopping disease progression as an end goal
30:48 – Louise: Does it matter that NASH is “a catalog of…system and health failures” when patients progress to cirrhosis?
32:07 – Donna on how she has lived with her IBD and how this applies in NASH
33:30 – Terri raises her Primary Care MD’s awareness of the diabetes -NAFLD link
34:36 – Donna discusses challenges GLI wants to present to FDA vs. those it does not want to present
35:29 – Roger: more important to see progress made on non-invasive diagnostics or getting a first drug to market, even with a not-great efficacy:safety ratio?
36:02 – Stephen discusses his reasons for selecting non-invasive testing and the steps he is taking to drive this discussion forward
37:37 – Stephen’s thoughts on FDA and its perspective on these issues
39:02 – Louise’s perspective on Roger’s question, those with "severe disease" will take more risks
40:07 – Donna: “It’s not just people with severe disease,” but anyone who understands the disease path, complications and challenges
41:05 – Donna: the patient’s goal is to have a full life, not merely avoid negative medical events.
42:16 – Roger is struck by the “paternalism” of institutional medicine
43:42 – Louise: this reminds me of the debate around false positives in testing
45:24 – Roger’s final question: what’s the one thing each of you wants to see come out of this?
45:34 – Terri, Louise, Roger answer
48:07 – Donna answers: “It’s not the answer that people are expecting…”
50:31 – Plans for AASLD coverage and the week after that, then Business Section
In the third conversation from SurfingNASH's AASLD 2021 preview, Manal Abdelmalek, Ken Cusi and Jörn Schattenberg join Louise Campbell and Roger Green to discuss a range of issues in the later days of the conference, all loosely related to NASH Patient Management.
Jörn starts this conversation by identifying some of the important presentations on clinical trials of novel therapies. From here, the group focuses on other Sunday and Monday presentations, some with a basic science focus and others that are more patient-oriented. In the end, the group answers Roger's final question, "If there's one impression that you expect, you might walk away from this meeting with, or an area where you really feel particularly enriched, what would that be?" Not surprisingly, the diversity of opinions and perspectives of the panelists is reflected in their final answers.
Manal Abdelmalek, Jörn Schattenberg and Ian Rowe join regulars Stephen Harrison, Louise Campbell and Roger Green to recap NAFLD and NASH-related insights from the 2021 TLMdX, the AASLD annual liver meeting. This conversation focuses on what we have learned about NITs and clinical development testing that will, in the words of Stephen Harrison, "put a big, fat dent in Fatty Liver disease."
The conversation starts with the group congratulating Manal Abdelmalek on her wrap-up NAFLD talk at the 2021 TLMdX. From there, the group focuses on the shortcomings of using biopsy as the clinical trial gold standard and how strategic clinical trial design and interpretation of existing NIT data can build a bridge from biopsy through MRE/biopsy correlations to a total NIT future.
In the second conversation from SurfingNASH's AASLD 2021 preview, Manal Abdelmalek, Ken Cusi and Jörn Schattenberg join Louise Campbell and Roger Green to discuss the breadth of NASH Drug/Disease Management on the weekend agenda.
Louise starts this conversation by pointing out Saturday sessions she believes will be important to understanding Fatty Liver care delivery, including sessions addressing women's health, health service and public health. From there, Ken leads into a discussion of Saturday's post-graduate course and Manal Abdelmalek opens a discussion on Sunday's Presidential Plenary session. She and Jörn note the importance of the presentation that explores longitudinal association between MRE and various outcomes, focusing specifically on the importance of deriving cardiovascular outcomes. Jörn and Roger comment on specific issues around the design of the aldafermin ALPINE 2/3 trial and the implications of clinical vs. commercial failure. As the conversation ends, Manal and Ken identify other science-driven sessions.
In the first conversation from SurfingNASH's AASLD 2021 preview, Manal Abdelmalek, Ken Cusi and Jörn Schattenberg join Louise Campbell and Roger Green to focus on some of the basic NASH Science presentations during the first two days of the meeting.
After some preliminary comments from Roger and others about Saturday's day-long post-graduate course in NAFLD and NASH, Manal kicks this session into high gear by highlighting the Hans Popper Basic Science State-of-the-Art lecture, with its focus on single-cell genomics and its ability to transform our understanding of disease pathogenesis. As Manal points out, this becomes tremendously important because drug trials so far have achieved success in half of the patients or less...and we do now know exactly why a drug will work in some patients and not others. The group proceeds to discuss other sessions with some ability to shape NASH science around the diagnosis, staging, or management of NASH patients.
Manal Abdelmalek, Ken Cusi and Jörn Schattenberg join Louise Campbell and Roger Green to discuss key presentations at AASLD 2021 and preview SurfingNASH's coverage of the event. This virtual meeting runs from November 12-15 and is scheduled on East Coast time.
Highlights include:
9:19 – Roger begins the conversation, by describing the AASLD program elements and what SurfingNASH will cover.
10:46 – Manal Abdelmalek kicks us off by focusing on Dr. Neil Henderson’s Hans Popper (Basic State of Science) Lecture and the relevance his talk will have meaning for NAFLD and NASH.
12:53 – Ken Cusi links this talk to Monday’s Emerging Trends Symposium on “Tailoring NASH Therapy.”
15:26 – Manal identifies Friday’s Liver Cell Biology SIG, with its focus on gut-liver access and gut microbiota triggering, as another source of knowledge and insight for future potential NASH therapies
16:45 – Jörn Schattenberg raises Parallel Session 10 on Diagnostics and Biomarkers of NAFLD (Sunday, 10:00a) which will focus on LITMUS work in which he participated. He goes on to describe the research and how it can drive better patient treatment in advance of medications.
19:05 – Louise discusses the Public Health and Healthcare Delivery SIG (Friday, 5:30p). She is excited that the session will discuss the foundational role a behavioral approach health can play, particularly in the absence of medications.
19:58 – Roger, Louise, Jörn and Manal mention Friday afternoon sessions of particular interest.
22:51 – Louise identifies “a couple of really good sessions on Saturday,” the Women’s Health Program (4:00p) and Parallel Session 2 on “Health Services and Public Health” (10:00a)
23:20 – Ken Cusi summarizes some high points of the post-graduate course.
25:34 – Manal kicks off our conversation of Sunday presentations by discussing two talks from the plenary sessions: the presentation of the Alpine 2/3 results by Stephen Harrison and the longitudinal association between MRE and liver-related and cardiovascular events in NAFLD. Jörn adds a though by noting the inclusion of CVD results and then discussing their meaning.
28:03 – Manal notes the presentation from the Million Veteran program,
28:33 – Roger discusses some speculation from the podcast around the time of the aldafermin withdrawal and expresses the hope we will learn whether aldafermin was more a clinical or commercial failure. Jörn questions whether the decision to read out biopsies at 24 weeks may have been part of the reason the trial missed its primary endpoint
29:42 – Louise points out Parallel Session 17 titled “NAFLD and NASH: Predicting Outcomes and Response to Interventions” (Sunday, 4:00p) and its possible connection to some recent podcast topics
30:08 – Manal refers to the diagnosis and biomarker session Sunday as an opportunity to delve deeper into machine learning and artificial intelligence, after which Roger and Manal discuss the insights that AI improves and those it does not.
32:14 – Ken raises the joint AASLD-ALEH symposium Sunday (1:00p) as an excellent opportunity to learn more about the challenges stakeholders face in Latin and South Ameria and the southwestern US.
33:29 – Jörn notes that the panel has not discussed the sessions covering clinical trials of novel therapies and identifies some trials of interest.
36:14 – Manal mentions a paper at Parallel Session #33, Experimental Advances in NAFLD (Monday, 3:00p) that looks at single-cell RNA sequencing in mice to identify that hedgehog signaling in hepatocytes is a critical early event for NAFLD fibrosis in humans.
37:25 – Ken expresses optimism about the quality of the meeting, departs.
39:01 – Louise, Jörn and Roger identify other sessions of interest on Monday.
42:23 – Final question focuses on what panelists anticipate will be the most powerful takeaway from the meeting.
46:33 – Business Section
Alina Allen and Ian Rowe lead the Surfers in considering biopathological shortcomings in fibrosis as a solitary endpoint. Their comments stem from Alina's presentation of the recent Mayo Clinic paper, "MRE for Prediction of Long-Term Progression and Outcome in Chronic Liver Disease: A Retrospective Study." In this conversation, Alina summarizes the paper, after which Stephen Harrison asks questions about availability of subgroup analysis.
This conversation focuses on flaws in biopsy as a measurement device and also in fibrosis as a solitary endpoint.
In the rest of the discussion, the group discusses challenges in proving that NITs can accurate measure and differentiate between different drugs in terms of therapeutic efficacy. One challenge is with the current metrics. We speak frequently about the challenges with biopsy and with fibrosis being an ordinal variable, but as Alina notes, being too tied for fibrosis means we focus solely on one measure of improvement and downplay others, such as steatosis.
The conversation is too rich and nuanced to be captured in a paragraph or two. This episode is worth two or three listens to capture all its points.
Alina Allen and Stephen Harrison spearhead a discussion on how MRE results can provide a foundation for developing Subpart H Clinical Trial Endpoints from non-invasive testing data. Their comments stem from Alina's presentation of the recent Mayo Clinic paper, "MRE for Prediction of Long-Term Progression and Outcome in Chronic Liver Disease: A Retrospective Study." In this conversation, Alina summarizes the paper, after which Stephen Harrison asks questions about availability of subgroup analysis.
For NASH to move "beyond the biopsy," researchers must develop reliable clinical trial endpoints using non-invasive tests. This conversation winds up centering around MRE's ability to provide those metrics.
It starts with two different points. Ian Rowe comments on the power of message in dealing with patients. Specifically, he notes that the word "cirrhosis" does not engender strongly emotional or motivated responses whereas the word "cancer" certainly does so. Next, Stephen Harrison asks how cleanly we can translate MRE results into transient elastography readings. Ian suggests the answer is "not very clearnly."
Then the meat of the conversation starts, as Stephen asks whether MRE and LSM can lead us to a viable Subpart H surrogate endpoint. For this to work, he notes, we would have to translate LSM and/or liver function readings into a metric that then translates into an outcome. Alina Allen notes that MRE has the benefit of producing consistently read results without the reader variability issues we find with biopsy. Stephen pushes further, noting that it would be a major step to link magnitude of effect to a one-level fibrosis change, Alina reveals that the number falls consistently around 19%. Alina notes that we have no similar relationship for MELD scores, but the group agrees in the end it should be possible to design trials around MRE-based outputs.
Alina Allen and Ian Rowe discuss how Liver Stiffness Measurements (LSM) can improve individual patient treatment in pre-cirrhotic and compensated cirrhotic patients. Their comments stem from Alina's presentation of the recent Mayo Clinic paper, "MRE for Prediction of Long-Term Progression and Outcome in Chronic Liver Disease: A Retrospective Study." In this conversation, Alina summarizes the paper, after which Stephen Harrison asks questions about availability of subgroup analysis.
Ian starts this section by noting the challenges in relying on fibrosis when managing individual patients practically and wonders whether LSM might do a better job here. Alina endorses this thought emphatically. She notes that while there may be a benefit in clinical trials to separate an F2 from an F3, F levels have minimal impact on clinical recommendations for pre-cirrhotic patients. Conversely, LSM provides guidance on how quickly a patient is progressing toward cirrhosis regardless of fibrosis level, which can affect aggressiveness of recommendations and frequency of monitoring, among other issues.
During this conversation, Ian shares that he is conducting community-based research with over 3,000 patients so far in Leeds. This study is revealing similar results, with liver stiffness predicting progression up to a "tipping point" at which liver function begins to matter more. This can become germane to any specialist or primary care physician when treating patients.
Toward the end of the conversation, Louise Campbell notes that these same metrics can help identify patients who are failing sooner, which will leave more time for compassionate palliative care and end of life planning.
Alina Allen and Ian Rowe join the Surfers to discuss the recent Mayo Clinic paper, "MRE for Prediction of Long-Term Progression and Outcome in Chronic Liver Disease: A Retrospective Study." In this conversation, Alina summarizes the paper, after which Stephen Harrison asks questions about availability of subgroup analysis.
This paper was recently published in the journal Hepatology. While previous Mayo Clinic work focused solely on NASH patients, this retrospective look focused on 1,200 patients with assorted liver diseases who underwent MRE for the first time between 2007 and 2009 and tracked patients through 2020. In this analysis, MRE had strong ability to predict future outcomes, with the strongest results predicting which patients with some level of fibrosis would progress to compensated cirrhosis. In this group, every one-level increase in LSM translate into slightly more than a two-fold increase in risk of cirrhosis. MRE also provides robust prediction of progressing from compensated cirrhosis to decompensation, with every one-level increase in LSM translating to a 22% increase in the likelihood of progressing to decompensation. Prediction is lower in predicting outcomes for decompensated patients, largely because at this point liver function assumes greater relevance than stiffness. As Alina states, "this is why we use a MELD score for transplantation priorities" and similar issues.
The other important point Alina makes (and Ian Rowe has made in past episodes) is that biomarkers provide continuous numbers to plot progression over time, as compared to fibrosis level which is ordinal with four levels, or other metrics that have a high zone, a low zone and a gray zone between them. Continuous variables are easier to track for individual patients and provide richer statistical analyses.
When Alina finishes, Stephen Harrison asks questions about population subtypes in this study. Alina points out that the northern midwest is fairly homogenous demographically and the clinical charts from which researchers derived data did not have genetic information.
Professors Alina Allen and Ian Rowe join the Surfers to discuss our ability to predict long-term outcomes using MR Elastography. The conversation flows around Mayo Clinic's recent Hepatology publication, "MRE for prediction of long term progression and outcome in chronic liver disease.
The ability to predict long-term outcomes using MR Elastography (MRE) and other non-invasive testing methods will be pivotal to drug development and, separately, to diagnosing, staging and monitoring patients. Alina presents highlights from Mayo's recent CGH paper and lends her own significant experience in this area. As we learned last year, Ian leads or is involved in large population-based studies in Leeds, with considerable focus on how NITs can support patient treatment most successfully and cost effectively. This is a topic where all five panelists can contribute from unique perspectives reflecting their own experiences.
Highlights include:
8:53 - Alina Allen begins to discuss recent Mayo Clinic publication "MRE for Prediction of Long-Term Progression and Outcome in Chronic Liver Disease."
10:22 - Source of data for this retrospective analysis
11:33 - Discussion of results starts by discussing accuracy in pre-cirrhotic patients
13:05 - Key point: biomarkers can tell us more because they are continuous numbers, not two or three level models
14:08 - Stephen Harrison asks for specific numbers that listeners can use as rules of thumb for prediction
15:08 - Alina -- a 1 point increase in kPa...more than doubles the risk of cirrhosis for pre-cirrhotic patients, increases risk of decompensation by 22% in compensated cirrhotics
18:53 - Ian Rowe describes results as "great because it speaks to the development of more personal risk stratification for patients."
19:53 - Alina expands on the benefit for clinicians who need to treat and manage individual patients more intelligently and cost effectively
22:08 - Ian describes a study he and his team in Leeds are conducting that addresses similar issues.
24:09 - Alina raises question of how to monitor sub-F2 patients in hepatology and even primary care clinics
24:59 - Louise Campbell: same metrics will allow us to individualize terminal care and palliation sooner for patients whose livers will fail. Leads to a more in-depth discussion with Ian on what should happen in the UK today vs. what is happening.
27:39 - Alina describes palliative care in the US as "an area that needs a lot more work" and raises some of the challenges
30:13 - Stephen asks whether we can reverse engineer or analyze these results for FibroScan. Ian reports that his data suggests this is a more complicated challenge.
31:41 - Stephen asks about implications for endpoint designation in pre-approval outcomes studies, then suggests an alternate design with endpoints based on MRE
33:10 - Alina agrees with idea, referring to Scott Friedman's point in S2 E51 about the genesis of NAFLD activity scores and fibrosis levels
34:45 - Alina: "I think this connection between what we currently use to what we need to move in the future is starting to get made" and paints a picture for what trials might look like.
36:15 - Stephen asks whether we know enough to propose a Subpart H endpoint that is not biopsy driven. He and Alina agree we are close to having one key endpoint proven: a 20% decreasae in MRE correlates to a 1 level decrease in fibrosis.
The entire panel enters a discussion around histopathology's shortcomings, ranging from the fact that the NAFLD Activity score does not correlate with liver function to inconsistencies in reading all elements of biopsy.
This conversation revolves around the challenges posed by histopathology's flaws. Scott Friedman reminds us that NAFLD Activity scores do not correlate with outcomes, Roger Green reminds us that coder reliability scores would not be accepted in marketing research and Stephen Harrison describes the impact of these flaws on investors and drug/device companies. In the end, Scott provides a peak at some of the topics his lab is exploring and the entire panel discusses what they consider key takeaways from this engrossing episode.
Stephen Harrison and Jörn Schattenberg join the conversation with questions that focus on patient treatment and drug development.
The ultimate payoffs from Precision Medicine will come in better targeted, streamlined drug development along with improve ability to deliver the right drug to each patient. In this conversation, topics range from how cells signal distress to the value imaging can bring and, finally, how being "yoked to biopsy" holds drug development back.
Scott Friedman reprises key elements from his Paris NASH talk, focusing on Precision Medicine and some key factors that affect hepatic function that Precision Medicine must address.
Scott Friedman describes Precision Medicine as "the right treatment or diagnostic for the right patient at the right time." In this precís of his Paris NASH talk, he discusses the factors that shape Precision Medicine for hepatic function, including genetics, microbiome, human genome and CAR-T development. He concludes this opening discussion by focusing on stellate cells, starting with the history of stellate cell research and how they got their current name, and going on to discuss senescent, or aging, stellate cells, the "ultimate bad boys" of liver disease.
Scott Friedman, the "Father of Fibrosis", and Jörn Schattenberg join the Surfers to discuss Scott's recent Paris NASH and National Liver Congress talks on Precision Medicine, imaging and liver function.
Scott Friedman's Paris NASH talk on Precision Medicine made a strong impression on Stephen and Jörn, along with our listeners. The conversation summary of that talk and Lars Johansson's (S2 E46.2) is the largest conversation and third largest post in the history of the podcast.
Scott joined us to discuss precision medicine, imaging, stellate cells and an array of additional topics. Highlights include:
4:08 – Scott Friedman discusses his career in studying fibrosis, stellate cells and a range of other liver function issues
9:13 – Session icebreakers: Scott’s fun fact and everyone’s good thing from the past week
12:46 – Stephen Harrison introduces Scott by discussing what he learned at Paris NASH
16:00 – Scott begins his remarks and goes on to discuss Precision Medicine in the context of liver disease
19:02 – Why it means so much that precision medicine includes precision of therapies
19:39 – How the stellate cell got its name
21:04 –The power of technologies lies in single cell sequencing and analyses, and what it means for “us stellate cell geeks”
23:49 – The importance of senescent stellate cells
24:45 – An exciting future for CAR-T cells
25:40 – Jörn Schattenberg asks whether and how we can target drug therapies to specific patients
26:38 – Scott: Pharmacogenomics are the “known” part of how precision might affect prescribing and drug selection in the future
27:46 – The importance of endophenotypes: liver samples look the same under the microscope may reflect quite different causes of disease
28:50 – The ambitious effort to develop software that takes the mass of patient information and distills it into a clear picture and simple recommendation
30:02 – Stephen: do we know enough to target therapies to specific types of patients
31:14 – Scott: What we know about PNPLA3 cells, their variants and patient diagnosis and treatment is a good example of what we can learn over time
32:08 – Does part of the solution lie in pinpointing how a cell signals distress?
33:16 – The significant role imaging can play in improving precision
34:25 – Implications of precision medicine for drug development, and how being “yoked to biopsy” and the NAFLD Activity Score hold us back
38:18 – Should we focus our endpoints more on liver function?
39:38 – Is biopsy the “Premarin of diagnostics” – so highly and unreliably variable that we cannot replicate results?
41:04 – Getting beyond the biopsy: the imperative, the path and the two major challenges
44:02 – Putting existing tissue samples to better use: availability of sample, past discussions, potential solutions, practical considerations
48:06 – “Very cool” research “cooking” in Scott’s lab
49:02 – The importance of mentorship
49:24 – “Final question” to wrap up session
52:52 – Scott: there are good reasons for optimism in our history
55:21 – Business section
Antaros Medical's Chief Scientific Officer Lars Johansson joins Stephen Harrison, Louise Campbell, and Roger Green to reprise the key points of his recent Paris NASH talk. In this section, panel members speculate on the largest, most important conceptual changes that the new imaging approaches can drive in disease knowledge and research.
This session begins with Lars discussing the value of 3-D MRI, a technique he discussed in Paris, as well as work he did not mention in Paris that looks at spleen volume. The conversation ends with each panelist answering two questions from Roger. First, he asks the panelists to "Dare to Dream" the one most significant advance each one hopes will ensue from these imaging advances. After this, he asks two final wrap-up questions. To Lars, he asks the most important messages listeners should take from this episode. To the others, he asks the most "mind-blowing" thing they heard.
Antaros Medical's Chief Scientific Officer Lars Johansson joins Stephen Harrison, Louise Campbell, and Roger Green to reprise the key points of his recent Paris NASH talk. This conversation revolves around the implications of Lars's comment that we should track and analyze functioning hepatocyte cells as an excellent marker for liver function.
This conversation starts with a comment from Louise Campbell that this entire approach might play a significant role in moving us beyond the biopsy. Lars agrees, noting that studying fibrosis and fat reduction places too much emphasis on "what shouldn't be" in the liver instead of focusing on "what should be," which are high functioning hepatocytes. To explore hepatocyte function, he discusses use of gadolinium contrast agents, more than 50% of which are taken up by hepatocytes. This provides a setting to combine dynamic functional inputs based on hepatocyte function with static measures based on stiffness and PDFF. This provides a truly dynamic look at liver disease, which is particularly important given the liver's ability to regenerate. Stephen spends the last few minutes of the conversation by discussing the results this approach can yield and contrasting it favorably to the techniques we use today, some of which are difficult to implement and none of which provide the richness of information achievable with the imaging techniques Lars describes.
Antaros Medical's Chief Scientific Officer Lars Johansson joins Stephen Harrison, Louise Campbell, and Roger Green to reprise the key points of his recent Paris NASH talk. In this conversation, Lars and Stephen discuss the value of assessing the balance of fibrogenesis and fibrosis in healthy and unhealthy livers.
Introducing our guest surfer, Stephen Harrison describes Lars Johansson's Paris NASH talk as "remarkable and intriguing." Lars begins his comments by discussing the use of PET tracers to target fibrosis through Collagen Type I cells as well as hepatic stellate cell activation through PDGFR beta. He and Stephen go on to discuss two critical ways the resulting insights can change drug development: first by identifying the correct circulating blood biomarkers to include in different trials or pieces of research, and second by optimizing combination therapies based on the specific effects each agent has on the fibrosis and fibrogenesis processes. On the latter issue, Stephen suggests this approach might have benefit not only in NASH but also a broader range of metabolic diseases Lars concurs.
Antaros Medical's Chief Scientific Officer Lars Johansson joins Stephen Harrison, Louise Campbell, and Roger Green to reprise the key points of his recent Paris NASH talk and comment on several other topics.
Lars Johansson's Paris NASH presentation, "Innovations in Imaging Assessment of Fibrosis"," introduced his audience to a dynamic, multidimensional view of tools that can show us how the liver works. Rather than focusing on static measurements of "what shouldn't be there," Lars discusses the measurement of "what should" - for example, the interplay of fibrosis and fibrogenesis. Most striking, he describes an array of leading edge and state of the art imaging techniques that shift focus from today's "what shouldn't" targets (fat and fibrosis) to "what should" (functioning hepatocytes, to give one example.) This different viewpoint combines with the novel imaging tools and approaches to create an episode that might leave you repeatedly thinking "Oh, Wow!" Expected to be challenged and exhilarated!
Highlights include:
12:27 - Stephen Harrison introduces Lars Johansson by discussing the Paris NASH meeting and the session Stephen chaired
14:29 - Lars begins his discussion of the Paris NASH paper
15:35 - The role of PET tracers in assessing disruptions in liver homeostasis through assessment of hepatic stellate cells and imaging collagen Type I
17:58 - Why Stephen sees the kinds of imaging Lars describes as "potentially a game changer" and his "next step": to associate these results with blood-based biomarkers
20:59 - Lars discusses the best interplay of circulating blood biomarkers and PET tracers, and highlights combination therapy development as an area for development
22:29 - Stephen suggests that this approach can provide more holistic solutions than histopathology, particularly for metabolic disease and specific sub-types
25:04 - Louise discusses the benefit to the patient of using these kinds of technique to move beyond much current biopsy
26:25 - Lars's "second piece from Paris" is the use of a gadolinium contrast agent due to its high level of hepatic uptake
27:41 - Roger observes that these tools allow us to study the liver as a dynamic system
28:24 - Lars discusses why to him, hepatocyte function is a robust dynamic measure
29:38 - Stephen speculates that these techniques can create knowledge more efficiently than our best measures today and suggests that they will provide greatest value in cirrhosis and advanced fibrosis
34:32 - Lars suggests these kinds of techniques might replace for augment HVPG over time and goes on to share an integrated version of how much data these approaches can produce in a single drug trial
36:22 - Louise's "Dare to Dream:" replace biopsy with an easier way to assess path of disease which will allow more efficient screening of more patients
37:12 - Roger's "Dare to Dream:" visualize the liver in the context of the whole patient
39:23 - Stephen's "Dare to Dream:" to become cognizant of how the range of noninvasive tests can help us mold drug development for different phenotypes of patients and separately, to speed drug development
41:09 - Lars's "Dare to Dream:" Bring these techniques to early drug development, which will streamline investment of time and money by improving focus
42:52 - Roger's final question - "The one thing that 'blew everyone's minds' the most."
46:40 - Business Section - A listener record; for the first time, a conversation gets more downloads than its episode, update on CME, requests for conferences you would like us to attend
Last author and leading endocrinology Fatty Liver Opinion Leader Ken Cusi joins co-author Stephen Harrison, Louise Campbell and Roger Green to discuss the recent Clinical Care Pathway published in Gastroenterology. This conversation answers the question "What Can Be Done Today?" in terms of screening and patient management without approved drugs.
The paper "Clinical Care Pathway for the Risk Stratification and Management of Patients with Nonalcoholic Fatty Liver Disease" is a clarion call to action, but what exactly should clinicians do? This conversation addresses that issue. Louise Campbell starts by stating that the World Health Organization should incorporate Fatty Liver disease into their diabetes initiative. Next, she leads the group into a discussion of the merits of transient elastography, which leads Ken Cusi and Stephen Harrison to discuss blood-based and imaging options clinicians can deploy when they lack access to a FibroScan or similar device. Finally, Roger asks the most important step stakeholders should take now, which provide an array of different actions.
Last author and leading endocrinology Fatty Liver Opinion Leader Ken Cusi joins co-author Stephen Harrison, Louise Campbell and Roger Green to discuss the recent Clinical Care Pathway published in Gastroenterology. This conversation centers on two issues: driving behavior change and recognizing the scope of the need.
For "Clinical Care Pathway for the Risk Stratification and Management of Patients with Nonalcoholic Fatty Liver Disease" to achieve its goals, clinicians need to be motivated to action and then understand what to do and why. This conversation discusses different philosophical and behavior economics motivators. Ken Cusi stated his excitement based on the belief that once a clinician starts to screen and sees one seemingly healthy patient with cirrhosis, he will treat differently. Roger Green pointed out three small items in the first paragraph of the paper that seem designed to say, "This is serious. Pay attention!" Finally, Ken and Stephen Harrison discuss their previous work in assessing prevalence, which demonstrated that disease is far more widespread than most people (clinicians and patients alike) believe and over the past 10 years, we may be seeing a dramatic increase in the number of seemingly healthy people with severe NASH.
Last author and leading endocrinology Fatty Liver Opinion Leader Ken Cusi joins co-author Stephen Harrison, Louise Campbell and Roger Green to discuss the recent Clinical Care Pathway published in Gastroenterology. This conversation centers on how the working group came to be and how they developed this pivotal paper.
The path to publishing "Clinical Care Pathway for the Risk Stratification and Management of Patients with Nonalcoholic Fatty Liver Disease" had its challenge, both in terms of forming the working group and then working through the key issues and questions for the paper. In this conversation, last author Ken Cusi addresses the first point and co-author Stephen Harrison addresses the second one. Between the two, Louise Campbell comments on how important this paper is to the future of Fatty Liver diagnosis and treatment.
Last author and leading endocrinology Fatty Liver Opinion Leader Ken Cusi joins co-author Stephen Harrison, Louise Campbell and Roger Green to discuss the recent Clinical Care Pathway published in Gastroenterology.
Last week, Gastroentrology published the article "Clinical Care Pathway for the Risk Stratification and Management of Patients with Nonalcoholic Fatty Liver Disease.This paper and its predecessor, "Preparing for the NASH Epidemic: A Call to Action," was the result of collaboration between leaders in endocrinology, diabetes care, bariatric medicine and obesity care, primary care, gastroenterologists and hepatologists. This paper presents a clear, straightforward multidisciplinary pathway for the identification, screening, diagnosis, risk stratification and management of NAFLD and NASH patients. It is truly a groundbreaking piece of work.
Dr. Kenneth Cusi, who served as last author on both papers, joins the Surfers to discuss the effort that went into development of the pathway and critical elements for its adoption and use.
Highlights include:
7:40 - Ken Cusi begins to discuss his history with Stephen Harrison and work on the Clinical Care Pathways paper
10:41 - Louise Campbell's initial reaction: "A pivotal piece"
12:29 - Stephen Harrison discusses the way the group worked together
13:54 - Ken's first goal: "to build the muscle" for non-hepatologists to think about Fatty Liver whenever treating a patient in the three targeted groups
17:26 - Stephen identifies a key discussion point in the group: identifying at-risk patients to target
18:48 - Why the group chose FIB-4 as its initial standard test
20:57 - Ken's hope: medical societies asking their clinician members to screen the three groups regularly for Fatty Liver
22:42 - Three items that struck Roger Green immediately
22:35 - Ken's "down to earth" study of asymptomatic patients
25:38 - Increasing awareness might drive two changes in prescribing behavior: doctors might select diabetes drugs with the liver in mind and not stop the patient's statins
26:46 - Stephen reviews the 2021 San Antonio prevalence study
29:54 - Stephen: What's changed since the 2011 San Antonio prevalence study? Moderate-to-severe NASH more than doubled!
32:00 - Louise: liver disease should become part of the WHO initiative on diabetes
33:07 - Ken explains elastography in simple terms
35:10 - Stephen discusses principles of screening for NASH patients with significant cirrhosis risk
36:07 - Stephen lists blood-based and imaging confirmatory options for clinicians who cannot access FibroScan or other in-office elastography
38:11 - Roger: How does this translate into the last 5 or 10 patients a clinician saw?
39:20 - Ken expresses optimism that new obesity drugs will motivate non-hepatologists to look for NASH harder and treat it more aggressively
40:41 - Louise raises two more questions
42:14 - Stephen's closing comments: we're at the beginning, like the Wright Brothers
43:32 - Louise's closing comments: education, education, education...and advocacy
44:22 - Ken's closing comments: share hepatologists' knowledge with other specialties to improve screening and care of Fatty Liver disease
46:04 - Roger's closing comment: if a journey of 1,000 miles starts with a single step, this is like starting with a marathon
47:17 - Business report -- CME credits for Surfing the NASH Tsunami, the reason for two sponsors and an exciting schedule ahead
Mazen Noureddin joins Stephen Harrison, Louise Campbell and Roger Green to close our series of "Biggest Stories of NASH Summer." In this conversation, Roger uses a classical Marketing Research question to help the group sort out the relative impact potential of the ideas they have been discussing.
This conversation starts with Roger Green using an old marketing research question. He asks each panelist to divide 100 points of potential to change between Stephen's multi-slide concept, drug development as exemplified by the EFX trial and advances in NITs as exemplified by MRE. The group each comes to different answers and uses different logic to get there. Listen to their thinking to decide what you can learn from each of them and where you disagree.
Mazen Noureddin joins Stephen Harrison, Louise Campbell and Roger Green to close our series of "Biggest Stories of NASH Summer." In this conversation, Louise Campbell raises two very different points about the earlier conversation.
Louise's first point has to do with steps taken to maintain compliance with clinical trials and whether researchers can analyze these in a way that will help front-line treaters understand what are keys to patient pharmaco-adherence. This leads to a conversation about why trials are managed the way they are and what it is reasonable to expect from front-line practices. Louise's second point asks us all to envision the biopsy the patient provides as a "gift" and to consider how we might treat samples differently if we viewed them that way. The conversation circles back to Stephen's multiple sample slide idea, with Stephen and Mazen discussing what the impact of this approach might be in terms of screen fail rate and placebo response. Finally, Stephen makes predictions for the Ole Miss - Alabama football game, which will have occurred by the time you listen.
Mazen Noureddin joins Stephen Harrison, Louise Campbell and Roger Green to close our series of "Biggest Stories of NASH Summer." In this conversation, Stephen Harrison starts by discussing some issues and insights around the use of FGF-21s and then "hijacks" the conversation to explore a standard practice in histopathology that he would like to change.
This conversation starts with Stephen talking about the differences between FGF-21s and discussing why these results are so compelling. He asks Mazen to comment on how he expects to use FGF-21s in practice and Mazen provides a thoughtful, nuanced reply.
At this point, Stephen shifts gears to ask why we do not produce more slides from a given liver sample. He and Mazen agree that they have wondered about this for a while and believe it would strengthen results. Speaking from more of a straight statistical perspective, Roger Green agrees.
Mazen Noureddin joins Stephen Harrison, Louise Campbell and Roger Green to close our series of "Biggest Stories of NASH Summer." In this conversation, Stephen Harrison provides an image to suggest the enormity of the coming NASH pandemic and Mazen identifies his two biggest stories of summer.
Mazen's "biggest things of summer" include Stephen's recent article on the efruxifermin Phase 2a trial that was published in Nature and the Mayo Clinic group's work on MRE. For the efruxifermin, he cites some remarkably positive trial results, with a second related point. The study was published in Nature Medicine, which is only now and its various publications are now looking to publish original clinical trial research on NASH and Fatty Liver disease. To Mazen, this demonstrates the growing focus on NASH as a coming challenge.
Earlier in this conversation, Stephen makes the same point a different way by noting that according to estimates published by some of our leading hepatologists, the number of NASH-related deaths from 2016-2030 in the US will dwarf the number of COVID-19 deaths to date.
On Mazen' second point, he discusses why MRE is such an important diagnostic testing method for clinical trials and why papers like this one will be so critical in moving "Beyond the Biopsy."
Stephen wraps up this conversation by noting how quickly Fatty Liver research and knowledge are developing on multiple paths, all in common.
Mazen Noureddin joins Stephen Harrison, Louise Campbell and Roger Green to close our series of "Biggest Stories of NASH Summer" with his own unique slant on recent events and publications.
Mazen's take on the 'Biggest Stories of NASH Summer" integrates the content of papers, the journals in which they were published and the attention they received to form a message that says, "Fatty Liver has more good news to report and more people who want to learn about it." Halfway through, Stephen Harrison "hijacks" the episode to ask a common sense question about how the Fatty Liver community uses slides from biopsies today. This leads to a conversation in which each participant comes at the issue from a dramatically different angle.
Highlights include:
8:49 - Mazen Noureddin begins to discuss his "Biggest Stor(ies) of Summer"
9:54 - Mazen focuses specifically on the efruxifermin (EFX) paper in Nature Medicine
12:56 - Mazen shifts focus to the recent paper from the Mayo Clinic group that used a retorspective study of MRE results and longer-term outcomes to demonstrate that MRE improve prognosis accuracy in CLD patients
15:24 - Stephen Harrison begins his response to Mazen
16:45 - Stephen discusses what he considers the most important lessons from the EFX trial
18:33 Mazen on where FGF-21s are likely to be used and what what duration
22:21 - Stephen "hijacks" the discussion to raise the idea of one H & E slide per biopsy.
25:12 - Mazen agrees with Stephen's statement about multiple slides
26:51 - Roger concurs from a probability sampling point of view
27:18 - Louise begins her reply by discussing the impact of side effects on patients, using Hep C as an earlier example, and the hope that clinical trials can more closely resemble care in everyday practice
29:06 - Stephen comments on why trials and clinical practice are so different and why it continues to be this way
31:38 - Mazen discusses FGF-21 side effects in the context of GLP-1s
32:47 - Louise notes that biopsy samples are valuable and costly to the patient (in terms of discomfort, at least) and that we show the patient respect by extracting the maximum possible value from each tissue sample
33:31 - Roger asks the historical logical for doing only one H & E slide per patient. Mazen speculates, then Stephen explains.
37:05 - Roger asks whether the goal is to improve screen fail rates and reduce placebo scores at the same time. Stephen confirms this.
37:58 - Roger asks group to assign scores to the relative importance of multiple slides, new medications and moving to NITs. Answers vary. The reasons are even more interesting than the answers themselves
Professor Manal Abdelmalek joins Louise Campbell and Roger Green to discuss the important Fatty Liver stories of the last few months. She focuses on NIH's recent decision to stand up and fund the Liver Cirrhosis Network.To Dr Abdelmalek, the NIH action signifies increased focus on the significant long-term consequences of Fatty Liver disease. She discusses a Q&A at a talk she gave this summer where a physician noted that drug development is exciting but three years in the future and asked, "What can I do for my patients NOW?" She cites a recent small, early-stage study that suggested a single dose of metformin might have an impact on portal pressure and goes on to suggest that statins and beta blockers might also have a role to play in treating compensated cirrhosis patients. Louise Campbell contributes a strategy for evaluating patients taking these older drugs using FibroScan and blood-based tests. This is an innovative way to look at providing immediate benefit for patients who need it most urgently.
Professor and epidemiologist Michelle Long joins Louise Campbell and Roger Green to discuss the important Fatty Liver stories of the last few months. She focuses on the recent paper on prevalence of NAFLD and NASH in an unselected middle-aged population.To Dr. Long, an epidemiologist, there has been very little high quality perspective research on NAFLD/NASH prevalence. She discusses why she considers the study a methodological advantage. She and Roger Green agree that the conventional wisdom, which posits a 25% incidence of NAFLD and that 25% of NAFLD patients have NASH, is probably far too low. Instead, they note, a more realistic NAFLD estimate might be 37% NAFLD and a more realistic NASH estimate might be 14%. This suggests a far greater need to screen quickly and aggressively across most patient segments. At that point, Louise Campbell joins the conversation to suggest a strategy to screen faster and more efficiently. All things considered, this conversation increases the salience of diagnosing and treating Fatty Liver disease and some ways to find patients.
Newly-appointed Professor Ian Rowe joins Louise Campbell and Roger Green to discuss the important Fatty Liver stories of the last few months. He focuses on the recent FDA approval of the ELF test for prognosis of cirrhosis.
To Professor Rowe, the ELF approval was the most important story of summer because it promises a brighter future for non-invasive tests and, eventually, decreased reliance on biopsy. Dr. Rowe points out that transitioning from the ordinal results that biopsy generates (fibrosis score level) provide limited, unrealistic guidance in determining the probability of a downstream negative event (transplant, cancer, death). He contrasts this to continuous test results, including blood-based and device-driven tests, which provide clearer guidance about downstream risks. Louise Campbell adds her own reflections about the importance of inexpensive, blood-based tests to address the emerging NASH pandemic in poorer Third World Countries. This is not a long conversation, but it looks at the issue from some unusual, enlightening angles.
Ian Rowe, Michelle Long and Manal Abdelmalek reveal what they consider the most important NAFLD/NASH stories of summer.
Which NAFLD/NASH stories did they choose? The newly-appointed Professor Rowe discusses the importance of the FDA approval of the ELF test as a prognostic for cirrhosis. True to her epidemiological background, Professor Long reviews the prospective prevalence study that Stephen Harrison, Naim Alkhouri and others conducted in San Antonio. Finally, Professor Abdelmalek uses a comment she received at a presentation this summer as a jumping-off point to discuss potential value currently available generic drugs -- metformin, statins, carvedilol -- in treating portal pressure among cirrhosis patients. Some highlights:
4:39 - Ian Rowe's understated announcement
6:31 - Ian's event: FDA approves ELF
9:49 - ELF (and other NITs) will improve risk stratification by replacing ordinal Fibrosis scores with continuous test results
11:37 - Louise Campbell raises the issue of testing for the increasing NAFLD/NASH prevalence in Third World countries with fewer resources than the West has
13:02 - Ian notes that widespread population screening must start with a simple, inexpensive test, even in wealthier countries
14:54 - Roger Green raises the value of visual (picture) test results and asks how blood-based tests can overcome the fact that they do not produce pictures. Discussion and friendly debate about relative value of risk scores and visual outputs ensues.
18:39 - Ian discusses his work on patients' understanding of cirrhosis, which demonstrates the value of nursing in cirrhosis care clinics. Louise amplifies his point.
22:34 - Wrap-up question for Ian's interview
24:20 - Conversation with Michelle Long begins
26:49 - MIchelle's event: Stephen Harrison and Naim Alkhouri's paper on "Prospective Evaluation of the Prevalence of Fatty Liver Disease and NASH in an Unselected Middle-age Cohort"
28:28 - MIchelle mentions NAFLD/NASH prevalence rates among study participants
32:35 - Louise revealed what she learned in a high-level qualitative scan of patient records
33:36 - Louise discusses recent paper on the long-term of simple steatosis
35:27 - Louise wonders about the level of NAFLD/NASH education and awareness among endocrinologists.
40:10 - Louise raises the idea of scanning patients who have come to physician for other procedures, just as Stephen did in the prevalence study
44:56 - Conversation with Manal Abdelmalek begins
47:40 - Manal's event: NIH funding the new liver cirrhosis network
49:22 - Manal focuses on the urgency of doctors and patient today, the need to propose helpful therapies. At 50:30, she discusses a recent single-dose 1000mg metformin study checking its effect on portal pressure in patients with cirrhosis.
53:35 - Manal notes that statins, beta blockers have some reported positive effects in cirrhosis
56:27 - Roger raises the idea of maintaining fibrosis level as a clinically meaningful endpoint for approval
59:28 - Louise describes a way that even general practice physicians can track cirrhosis using their FibroScan machines or other equipment
1:03:19 - Manal raises the idea that this is drug help we can provide for some patients now, before approval
1:07:19 - Closing question for the third conversatio
Jörn Schattenberg joins Stephen Harrison and Roger Green to review some highlights from last week's Paris NASH meeting. This conversation looks at the Day Two sessions and the overall implications of the meeting.
Paris NASH is a meeting for basic science and interdisciplinary thinking. While the first two conversations of this series focused specifically on one or two sessions, this one takes a broader view and searches for high-level lessons and questions. From the second day, Jörn Schattenberg chose to mention several talks he felt made particularly important points and a session "NASH Around the World" that demonstrate the scale of the global challenge by looking at major countries around the world. Finally, Stephen Harrison and Roger Green joined Jörn in selecting one key takeaway from the meeting and our conversation.
Jörn Schattenberg joins Stephen Harrison and Roger Green to review some highlights from last week's Paris NASH meeting. This conversation looks at the session covering fibrosis.
Paris NASH is a meeting for basic science and interdisciplinary thinking. Since Stephen Harrison was drafted into co-chairing the session titled "Deep Dive into Fibrosis," he led this conversation. The session included three presentations with a powerful collective message about stellate cells: that different stellate cell subtypes perform in unique ways in terms of how they function, the process(es) through which they become modified and what this represents in terms of performance. This description does not do Stephen and Jörn's comments justice. It's a short session, so listen for yourself...
Jörn Schattenberg joins Stephen Harrison and Roger Green to review some highlights from last week's Paris NASH meeting. This conversation looks at sessions covering epidemiology, public response and clinical questions.
Paris NASH is a meeting for basic science and interdisciplinary thinking. As Jörn Schattenberg reviews the first two sessions of the meeting, he covers both these territories. The first session started with Professor Jeffrey Lazarus discussing some of the same issues he covered as our guest on S2 E40 of SurfingNASH. The other presentations in the first session covered economic theory and automated care models, which led Stephen Harrison to share his own thoughts on the importance of building an integrated model for clinical trials. The second session of Paris NASH discussed clinical aspects of disease. Jörn focused on a paper discussing how NASH itself varies among different patient phenotypes and what that could imply in terms of diagnostics, patient treatment and drug development.
Jörn Schattenberg joins Stephen Harrison and Roger Green to review some highlights from last week's Paris NASH meeting, an event with exciting scientific messages and insights.
If you missed last week's Paris NASH meeting, you missed some exciting presentations featuring fresh, pivotal insights about Fatty Liver diseases and some new approaches to learning about this disease. Jörn Schattenberg and Stephen Harrison combine to provide a robust synopsis of the meeting while Roger Green asks a few questions and keeps the discussion in-bounds:
10:20 - Jörn introduces Paris NASH and discusses some of its basics, followed by introduction of Session 1: Epidemiology and the Public Response
14:07 - Stephen discusses potential for integrating home healthcare visits into clinical trials
17:15 - Session 2: Clinical Aspects
17:52 - "NASH does come in different flavors." Are we thinking about NASH with sufficient granularity?
20:32 - NASH pathogenesis and its link to other metabolic diseases
21:32 - Session 3: Deep dive into fibrosis
24:30 - Talk on "Innovations in imaging assessment in fibrosis" raises pivotal questions about advances we can make in cellular-level understanding
26:57 - Talk from Scott Friedman on "Common mechanisms, molecular evolution and resolution of fibrosis in NASH" yields several key ideas
28:45 - The importance of understanding stellate cell subtypes
33:37 - Jörn and Stephen select some key moments from Day Two
35:45 - Innovations in clinical trial bring researchers to consider competing risks and challenges in determining causes of mortality in NASH trials
40:26 - Session 8, "Global NASH," describes the size and scale of the NASH challenge around the world
Global Liver Institute President and CEO Donna Cryer joins Roger Green to discuss why recent EASL guidelines around use of non-invasive tests (NITs) in Fatty Liver diagnosis and disease tracking is such an important step for patients and treaters alike.
To Global Liver Institute President and CEO Donna Cryer, the recent EASL Guidelines on use of non-invasive testing (NITs) represent a major breakthrough in GLI's ongoing "Beyond the Biopsy" campaign. In this one-on-one interview with Roger Green, Donna discusses the rigorous, multidimensional approach that GLI has taken to championing NITs in drug development and patient treatment. The conversation eventually pivots to a discussion of the benefits, drawbacks and challenges associated with gaining a cirrhosis indication for drugs in development.
Fatty Liver Foundation President Wayne Eskridge joins Louise Campbell and Roger Green to discuss why he is so enthusiastic about the FDA's recent approval of the ELF test as a prognostic test for cirrhosis.
To Fatty Liver Foundation President Wayne Eskridge, FDA's recent approval of Siemens's ELF test as prognostic for cirrhosis is only the first step in the process of placing non-invasive tests (NITs) at the heart of all Fatty Liver Disease diagnosis, classification and staging. Wayne and Louise Campbell agree that more widespread use of NITs will make tests and their results accessible not only to patients but also their front-line primary care physicians. To Wayne, this improves patient experience, journey and behavior dramatically. To Louise, it makes her mantra of "If in doubt, rule it out" a realistic strategy for including liver as part of a broad evaluation of patients with non-communicable metabolic diseases.
NASH kNOWledge President Anthony Villiotti joins Louise Campbell and Roger Green to highlight two recent publications about NAFLD/NASH prevalence (underestimated!) and patient awareness (miniscule!) and what that portends for the future,
To NASH kNOWledge President Anthony Villiotti, two recent publications reveal that conventional estimates of NAFLD and NASH prevalence in the US may be as much as 50% too low and, simultaneously, that very few patients are aware they have the disease or what it means for their long-term prognosis. Tony and Louise Campbell agree on the importance of educating children starting in their early years of schooling. Tony also comments on his belief in grass-roots educating and hopes that as the COVID-19 pandemic abates, he will have more opportunities to do so. Louise talks about the need to educate/motiave primary care practitioners and related specialists to test more frequently and learn about the role the liver plays in non-communicable metabolic diseases they treat more frequently.
Louise Campbell and Roger Green interview patients/patient advocates Donna Cryer, Wayne Eskridge and Anthony Villiotti about what each considers the biggest NAFLD story of the summer.
The Biggest NAFLD/NASH story of the summer? Each had different ideas. To NASH kNOWledge President and Founder Tony Villiotti, the biggest story combined two recent publications that cross-validated the ideas that NAFLD and NASH incidence in the US maybe be 50% higher than is conventionally estimated...and that less than 10% of people with disease know about their conditions. To Fatty Liver Foundation President Wayne Eskridge, the FDA's appoval of Siemens' ELF test signalled both a breakthrough and a promise for non-invasive testing. Finally, Global Liver Institute Founder and CEO Donna Cryer considered the overall movement toward her goal of "beyond the biopsy" the story and the various data points, ranging from the new EASL guidelines to a lessened need for transplant hepatologists in training to perform as many biopsies during their training, as proof of the larger issue. In different ways, each conversation focused on the need to improve and expand patient and professional education. Still, this was a "the glass is half full" kind of conversation. Enjoy it:
3:31 - Conversation with Anthony Villiotti, President of NASH kNOWledge, begins
4:01 - Tony introduces his two feature articles on prevalence and low levels of patient awareness
6:07 - Roger notes parallels between the two papers in terms of incidence estimates, and also in that very few patients were aware of NASH
8:18 - Three challenges implicit in these study results
10:23 - Louise praises NASH kNOWledge for their commitment to educating children about their livers
13:18 - It does not require much time or effort to stimulate a school child physically while at school
14:42 -- Engaged liver supporters can build momentum wherever they are
17:59 - Wrap-up question: What might change?
21:58 - The Three Legs on the Stool of Treatment Urgency
25:48 - Wayne Eskridge begins by discussing his elation at the recent ELF approval.
28:02 - Will new NITs improve the HCP's desire to diagnose?
30:21 - With this approval and the MRE KPA predictive analytics, are we starting to develop an integrated approach to cirrhosis diagnostics?
33:13 - NITs matter more once we commit to look for simple steatosis
34:38 - Cirrhosis, NASH and the patient journey
36:31 - Patient journey and the start of feeling better
40:08 - Implications of some NITs having noticeable levels of false positive tests.
47:41 - In private health systems, is the patient the actual boss?
48:25 - Donna Cryer begins
49:08 - Donna's lead story? The EASL Guidelines on non-invasive testing
51:54 - The sequence of new technology product adoption
54:05 - Recommendation on how to use NITs
55:30 - The importance of internal data management, as the press person spoke with Elana
57:54 - FDA is beginning to acknowledge how well children respond to Santa.
Donna Cryer joins the Surfers to discuss how the COVID-19 Delta Variant is affecting Fatty Liver Disease in 2021. This conversation focuses on the current and potential impact of the Delta and future variants on clinical trial performance.
Seventeen months ago, Surfing the NASH Tsunami began as a podcast focused on how COVID-19 and the pandemic would affect NASH clinical trials. Some 90 original episodes later, we return to this subject in this conversation. Roger Green asks questions about how COVID-19 has affected clinical trial conduct in the US and other major markets and the rest of the Surfers provide answers about the current and future benefits from what we have learned managing trials in this pandemic. Keep listening to hear some potentially sobering comments on the effect Delta or a possible more potent future variant might have on patient recruitment and assignment. At the end, the four panelists all discuss one point listeners should take away from this conversation.
Donna Cryer joins the Surfers to discuss how the COVID-19 Delta Variant is affecting Fatty Liver Disease in 2021. This conversation focuses on vaccine confusion (taking the flu vaccine, the meaning of full approval) and the importance of global COVID-19 vaccine equity and policies that support it.
This conversation has several moments of debate, one around the likely strength of flu season in the US and another around how strong the impact of Pfizer/BioNTech's full FDA impact is likely to be in the US. On the flu discussion, Stephen Harrison follows up Donna Cryer's advocacy for all patients to take the flu vaccine by suggesting that the US will have a light flu season this year. The group does on to debate how much impact full vaccine approval is likely to have in the US and what will drive the increase in vaccinations that does occur. Finally, Donna Cryer and Roger Green discuss the case for vaccine equity, with both panelists noting that the larger portion of the cost of vaccinating countries with large, underdeveloped rural populations will lie in creating the distribution systems necessary to get treatment to patient, NOT in manufacturing the vaccine.
Donna Cryer joins the Surfers to discuss how the COVID-19 Delta Variant is affecting Fatty Liver Disease in 2021. This discussion focuses on the case for post-jab immunologic testing for compromised patients and goes on to explore what the US can learn from the UK's experience with the COVID-19 vaccine.
Donna Cryer starts this episode by discussing the vital importance of conducting post-vaccine immunologic testing in immunocompromised and liver transplant patients. As Stephen Harrison asking questions, Donna makes the discussion particularly powerful by sharing her own experience (zero immune response from her first two doses) and some of the emotional issues she experienced when thinking about testing. After this discussion, Louise Campbell discusses the UK vaccination program to date and lessons the US can learn from it.
Donna Cryer joins the Surfers to discuss how the COVID-19 Delta Variant is affecting Fatty Liver Disease in 2021. This discussion focuses on the process of moving immunocompromised and transplant patients to the front of the booster dose queue.
After Roger Green sets the preamble for this discussion of COVID-19 Delta variant and Fatty Liver Disease, Donna Cryer kicks the discussion off by discussing how immunocompromised and liver transplant patients, who had low priority for the initial COVID-19 vaccines, moved to the front of the line for the booster doses. This is a story of communication, collaboration and just plan hard work to make certain that the data necessary to make this case was completed and communicated properly.At the end of the conversation, Stephen Harrison discusses an article from Raj Reddy in the Journal of Viral Hepatitis that makes many similar points about what we have learned about the liver (with some special focus on Fatty Liver Disease) during the first year of the COVID-19 pandemic.
Donna Cryer joins the Surfers to discuss the different effects that the Delta Variant of COVID-19 is having on different stakeholders within the Fatty Liver community.
What impact is the Delta Variant of COVD-19 having on NAFLD and NASH? Let us count the ways in this lively, fast-paced episode with Donna Cryer and the Surfers:
16:11 - Global Liver Institute's efforts to drive priority vaccine position for transplant and severely immunocompromised liver patients
22:12 - Creating the GLI Patient Insight and Data Center
28:26 - Relevance and importance of post-vaccine immunology testing in immunocompromised liver patients
33:11 - Perspectives from comparing UK and Israel data and studying the UK experience more generally
41:51 - The importance and limits of impact from FDA's full approval of the Pfizer-BioNTech vaccine
47:42 - Why Global vaccine equity is so important to the future of the pandemic
50:20 - How experience with COVID-19 has improved clinical trial processes and procedures
54:30 - How much will Delta and future variants slow the rate of clinical trial progress?
Jörn Schattenberg joins the Surfers to discuss drug development in cirrhosis. This conversation constitutes a call to action for the Surfers and our listeners.
In terms of cirrhosis and drug development, the earlier conversations identified two goals: Focus on NASH cirrhosis as a possible an easier and faster path to approval than the traditional "start with F2/3" approach, and push to move the codification of disease knowledge and best practices from guidance documents that might be upgraded every five years to a real-time, on-line document similar to what we see today in Hepatitis C. As the conversation wraps up, all four panelists (Stephen Harrison, Louise Campbell, Jörn Schattenberg and Roger Green) consider what they each might do to push these ideas forward. If you are captivated or even intrigued by the earlier parts of the episode, listen to this conversation asking what you, yourself, can do to help bring about the changes Fatty Liver stakeholders need.
Jörn Schattenberg joins the Surfers to discuss drug development in cirrhosis. This conversation focuses on how to drive a broader change in perspective.
Once we accept the idea that cirrhosis can make an excellent target for drug development driven using non-invasive testing, the question is take the lead in bringing the appropriate initiative forward. Stephen Harrison points out that principal investigator KOLs are the group with the most knowledge and perspective but later notes that work-life balanced for these exceptionally busy people might limit their involvement. The group considers other stakeholders until Louise Campbell asks a question toward the end of this conversation that shifts panelists' focus from traditionally, static guidance documents to a continuously updated living document similar to what exists for Hepatitis C.
Jörn Schattenberg joins the Surfers to discuss drug development in cirrhosis. This conversation focuses on why F4 might be a better target than F2/3.
This conversation focuses on specific reasons that initiating drug development in cirrhosis might offer unique benefits against the traditional model. Stephen Harrison starts off by discussing changing views of which cirrhosis patients are mostly likely to respond. After some comments from Louise Campbell about patient engagement, Stephen and Jörn Schattenberg discuss reasons that improvements in non-invasive testing, and particularly MR Elastography, might make cirrhosis the preferred target for drug development. As Stephen and Jörn explain, cirrhosis might make an easier target for the transition from a biopsy standard to an NIT standard, and both FDA and EMA have indicated that a drug could receive full approval based on a Phase 3 cirrhosis result, instead of the conditional approval the agencies are willing to grant in F2/3.
Jörn Schattenberg joins the Surfers to discuss drug development in cirrhosis. This conversation focuses on the unique challenges in treating NASH cirrhosis.
This conversation focuses on challenges in treating patients with NASH cirrhosis and implications for drug development. Jörn Schattenberg begins by discussing several of the elements that make treating patients with NASH cirrhosis especially challenging because treating cirrhosis is challenging, treating NASH is challenging and NASH cirrhosis presents complications of its own. Stephen Harrison continues the discussion by considering drug development, starting with the historic view that we develop drugs for advanced fibrosis first and cirrhosis later. He then raises several reasons this perspective might be changing.
Jörn Schattenberg joins the Surfers to discuss drug development in cirrhosis, which evolves into a discussion about how to drive NITs forward.
Historically, NASH drug development strategy has started in advanced fibrosis with the goal of progressing to cirrhosis next. This episode suggests an entirely different approach.
The episode starts by discussing the complexities of treating cirrhosis and evolves into a discussion on why compensated cirrhosis might be the BEST place to achieve fast, successful drug development today.
Key moments include:
10:12 - Why discuss cirrhosis?
11:40 - Challenges in cirrhosis treatment and drug development
13:08 - A changing viewpoint on cirrhosis as drug development target
17:24 - NASH and cirrhosis disease progression
20:10 - Diagnosing and stratifying cirrhosis patients
24:20 - NITs might make cirrhosis a better drug development target than F2/3
30:06 - Building momentum to reconsider NASH and cirrhosis drug development
33:47 - Identifying the conceptual road block in the move toward NITs in cirrhosis
39:09 - Formulating a plan of action to strengthen cirrhosis drug development and treatment
40:53 - A "disruptive technology" to pool clinical trial results
44:28 - The challenge: pushing cirrhosis treatment and drug development forward
50:09 - Business section
Professor Arun Sanyal and Stephen Harrison provide a 40-minute briefing on fibroblast growth factor (FGF) agents and why they are so important to the future of NASH and NAFLD therapy. This conversation detours into health policy and screen fail rates before returning to consider the 2-5 year implications of FGF drug therapies.
After a simple opening from Roger Green, this conversation includes 4 key elements:
Health Policy
1:24 - Arun Sanyal discusses directions that Fatty Liver policy in India is heading, along with some its unique features (for example, focus on rural health)
2:58 - Louise Campbell discusses the gap between how the best British programs (as identified in Jeff Lazarus's paper) organize and operate as compared to what the recent British Liver Trust study tells us about overall Fatty Liver care in the U.K. After Roger makes a commitment to return to health services policy in future episodes, Louise asks a question about how high screen fail rates appear to be in this study. Stephen Harrison notes that these are not particularly high for a NAFLD or NASH study and explains why.
7:28 - Roger asks his final question, which is how panelists believe FGF 21s will be used 5-7 years from today. Arun Sanyal provides the first answer, which looks at FGF-21s and NASH in the context of metabolic diseases and discusses how GLP-1 and SGLT-2 agents that were originally indicated solely for Type 2 Diabetes have broadened indications and use by demonstrating benefit in related non-communicable metabolic diseases,
10:05 - The other panelists add smaller points to Arun's exceptional and global statement. Stephen concurs completely with one important addition: If FGF-21s demonstrate potent anti-fibrotic effects in NASH patients, this will give them a unique role in first line therapy. Louise follows up with her belief that uptake of these agents might mimic some of the Hep C drug and Roger concludes by saying that the entire range of FGF effects is not widely known and, as a result, it is difficult to predict how widespread use might be.
Professor Arun Sanyal and Stephen Harrison provide a 40-minute briefing on fibroblast growth factor (FGF) agents and why they are so important to the future of NASH and NAFLD therapy. This conversation focuses on the roles fibroblast growth factors (FGFs) play in fat metabolism, appetite and other issues related to Fatty Liver disease.
After a simple opening from Roger Green, this conversation includes 4 key elements:
1:06 - Arun Sanyal discusses the different ways that fibroblast growth factors work in the body
4:21 - Stephen Harrison share some background on how fat gets into the liver in the first place
6:16 - Arun Sanyal describes the specific differences between FGF 2, 3 and 4 receptors in terms of physiologic impact and the role of adiponectin
9:50 - Stephen Harrison and Arun Sanyal comment briefly on the impact of adiponectin in terms of liver scarring
Professor Arun Sanyal and Stephen Harrison provide a 40-minute briefing on fibroblast growth factor (FGF) agents and why they are so important to the future of NASH and NAFLD therapy. This conversation focuses on FGF drug development to date.
After a simple opening from Roger Green, this conversation includes 4 key elements:
1:05 - Roger Green discusses recent history of FGF agents and podcast episodes discussing them
2:11 - Stephen Harrison discusses the efruxifermin BALANCED Phase 2a trial in F2/F3 NASH and Cohort C with cirrhosis patients
6:59 - Arun Sanyal and Stephen Harrison discuss future prospects for FGF-21 agents
10:34 - Arun Sanyal discusses specific receptor targets for different FGF agents and why they matter
This episode has specific discussions of efruxifermin and mentions of pegbelfermin and MK-3655, the former NGM-313.
Professor Arun Sanyal and Stephen Harrison provide a 40-minute briefing on fibroblast growth factor (FGF) agents and why they are so important to the future of NASH and NAFLD therapy.
This discussion combines a discussion of the role Fibroblast Growth Factors (FGFs) play in the liver and human body in general, followed by a discussion of what this implies for drug development in general and some of the specific agents currently in testing or market:
0:15 - Opening quotes - Stephen Harrison, Arun Sanyal, Roger Green
2:07 - Episode begins
2:57 - Meet Professor Arun Sanyal
4:47 - Quick Look at Health Systems and Policy: India, UK, future episodes - Arun, Louise Campbell, Roger
8:16 - Icebreaker and episode set-up - Roger and panel
13:07 - Efruxifermin trials - Stephen Harrison
18:00 - How FGFs work -- Arun Sanyal
21:13 - Liver pathophysiology and insulin resistance -- Stephen and Arun
28:13 - Q & A comparing agents in development - Roger, Louise Campbell, Arun and Stephen
42:09 - Roger offers two choices for the episode's Final Question. Arun provides an exceptionally thoughtful and thought-provoking answer.
The discussion itself includes three elements: first, a discussion of recent efruxifermin trials; second, a discussion of how FGFs work in the liver and rest of the body; and third, comparing and contrasting the various FGF-21 and FGF-19 drugs that are in development (or have been discontinued).
Co-authors Ken Cusi and Stephen Harrison discuss reasons to be optimistic and activist about the multidisciplinary call to action regarding the coming NASH Epidemic while NASH kNOWledge President Anthony Villiotti, Global Liver Institute Director of Global Policy Andrew Scott and Roger Green share their unique personal perspectives and Louise Campbell comments separately.
This conversation starts with Stephen Harrison suggesting messages for the government and Roger Green and Andrew Scott considering new opportunities to create metrics and benchmarks to measure success. All this relates to the effort in bring gastroenterologists, endocrinologists, hepatologists and primary care physicians together to fight what they describe as the coming NASH Epidemic. Paper co-authors Ken Cusi and Patient Advocates Tony VIlliotti and Louise Campbell share their own views (Louise's statement were extracted from a separate interview).
Co-authors Ken Cusi and Stephen Harrison discuss critical success factors in the multidisciplinary call to action regarding the coming NASH Epidemic while NASH kNOWledge President Anthony Villiotti, Global Liver Institute Director of Global Policy Andrew Scott and Roger Green share their unique personal perspectives and Louise Campbell comments separately.
This conversation starts with Roger Green asking what it will take to bring gastroenterologists, endocrinologists, hepatologists and primary care physicians together to fight what they describe as the coming NASH Epidemic. Paper co-authors Ken Cusi and Stephen Harrison and Patient Advocates Tony VIlliotti, Andrew Scott and Louise Campbell share their own views (Louise's statement were extracted from a separate interview).
Co-authors Ken Cusi and Stephen Harrison discuss how the multidisciplinary call to action regarding the coming NASH Epidemic came to be, while NASH kNOWledge President Anthony Villiotti, Global Liver Institute Director of Global Policy Andrew Scott and Roger Green share their unique personal perspectives and Louise Campbell comments separately.
This conversation starts with Ken Cusi providing background on the effort to bring gastroenterologists, endocrinologists, hepatologists and primary care physicians together to fight what they describe as the coming NASH Epidemic. The other panelists offer observations from their diverse perspectives.
Roger Green and Louise Campbell discuss some of the key elements of the "Preparing for the NASH Epidemic - a Call to Action" paper itself along with the discussion during Surfing NASH Episode 41.
Louise focuses on several of her professional passions and key beliefs: the importance of affiliated health professionals (Nurses, Dieticians, Nurse Practitioners, Physician Assistants) in providing care for non-communicable diseases; the vital need to empower patients, the value of focusing on wellness before the patient experiences disease. A couple of key moments:
1:52 - Louise discusses what she considers the most compelling benefits of the paper: collaboration between multiple specialties
3:35 - Louise notes that while the paper sought multiple stakeholders, all those stakeholders were physicians. No nurses, no dieticians, no affiliated health professionals, no patients.
6:43 - Louise amplifies this point by discussing the quantity and quality of information patients will share with a nurse as compared to a doctor.
11:03 - Louise suggests we take the "patient, ask your doctor" model and "flip it on its head." Public information and consumer-accessible medical technologies provide the tools for patients to manage their own wellness in ways they could not have only 10 or 15 years ago.
18:18 - Louise points out how Stephen Harrison has applied his KISS rule ("Keep It Simple, Stupid") to how we approach patient screening and triage.
Co-authors Ken Cusi and Stephen Harrison discuss the multidisciplinary call to action regarding the coming NASH Epidemic, how the first paper came to be and what lies behind it, while NASH kNOWledge President Anthony Villiotti, Global Liver Institute Director of Global Policy Andrew Scott and Roger Green share their unique personal perspectives on the need for diverse health professionals to align against Fatty Liver disease.The first part of this episode addresses the history and key contents of the recent paper, "Preparing for the NASH Epidemic: A Call to Action," in press or appearing in several major journals:
8:53 - Ken Cusi discusses the genesis and goals of the multi-disciplinary NASH initiative, which organizations participated and the questionnaire that lies at the heart of the paper. Stephen Harrison elaborates on goals and Tony Villiotti shares his perspective as a cirrhosis patient who underwent liver transplant
13:34 - Stephen Harrison discusses the recent prevalence paper suggesting that current population estimates of NASH and NAFLD may be understated. Ken Cusi agrees.
16:29 - CRITICAL SUCCESS FACTORS: Stephen Harrison discusses the dual needs for an approved drug and a consensus approach. Roger Green mentions the need to distribute care so that hepatologists are neither triage nor point of entry for NAFLD patients. Ken Cusi uses data from the 751-person survey to demonstrate how low NASH awareness is even among specialists (notably endocrinologists) and reaffirms the need for a therapy.
23:08 - Stephen Harrison shifts the discussion to focus on promising signs for the future, including integration of key stakeholders' discussions and efforts, the ability to identify and create care metrics and the importance of story-telling in making a persuasive case to power centers ranging from medical organizations to Capitol Hill.
31:37 - Discussion shifts to similarities and differences between treating diabetes and NAFLD and the role of the endocrinologist in each. Ken Cusi and Andrew Scott discuss why they believe diabetes is a good model for developing knowledge and treatment protocols. The group discusses ways that endocrinology might be fertile territory and, at the same time, will require significant professional education and increases in awareness.
40:03 - Tony Villiotti return to the importance of story-telling and personal experiences as powerful motivating tools.
41:51 - The group concludes by considering the tipping points and behavior changes we can drive today, before the first drug comes to market.
MONEY QUOTE: "Roger, I've heard you say the liver is the Rodney Dangerfield of organs, and you know it's true." - Anthony Villiotti
Jeff Lazarus and Roger Green discuss the ease of creating valuable metrics in a comprehensive care model, while our three practitioners -- Stephen Harrison, Jörn Schattenberg and Louise Campbell -- dive further into how they believe this model will improve care.
KEY POINT: Broadening the number and diversity of health care providers assigned to each individual patient will improve care by improving focus on the areas that count. It is important that system designers ask the right questions and answer them rigorously in context; it is undesirable for the systems to look more or less identical.
Stephen Harrison and Louise Campbell discuss their reactions to the recent paper, "Defining Comprehensive Models of Care for NAFLD." Stephen takes the perspective of a practicing hepatologist, Louise takes the perspective of a hepatology nurse, and both come to this discussion as NASH leaders and advocates.
The combination of practical patient treatment experience and passionate advocacy for NASH treatment through pharmacological and behavioral means shines through as Stephen and Louise express their enthusiasm for the comprehensive care approach and eight key elements.
Lead author Jeffrey Lazarus and co-author Jörn Schattenberg join the Surfers to discuss how they developed the care models for their recent paper, "Defining Comprehensive Models of Care for NAFLD."
The authors researched care models around the world to find the ones that work best, and then developed eight foundational recommendations for co-ordinated NAFLD care centers. In this conversation, lead author Jeff Lazarus discusses the influences on his career that converged in his decision to help shape comprehensive care models for the coming NASH pandemic. Next, co-author Jörn Schattenberg described the challenges the solo hepatologist faces when treating NASH patients today, and how this kind of comprehensive systems approach will help him offer better care.
Lead author Jeffrey Lazarus and co-author Jörn Schattenberg join the Surfers to discuss their recent paper, "Defining Comprehensive Models of Care for NAFLD." In this vitally important paper, the authors researched care models around the world to find the ones that work best, and then developed eight foundational recommendations for co-ordinated NAFLD care centers.
Jeff Lazarus brings a career of experience in analyzing and building health systems and, separately, in viral hepatitis and HIV to exploring the challenges of the upcoming NAFLD epidemic. He invited Jörn Schattenberg, among others, to serve as the team for this project. Jeff and Jörn discuss what a systems approach to NAFLD care looks like and what each of them learned along the way. Stephen Harrison, Louise Campbell and Roger Green each brig their unique perspectives about the practice of hepatology, issues of NAFLD and general systems theory to a stimulating discussion with an array of issues and answers.
This week's celebration podcast featured interviews including seven of our favorite Surfers. In this week's conversations, we are publishing the interviews in full. Third up, Jörn Schattenberg and Ian Rowe
Louise Campbell and Roger Green interview two frequent podcast guests, Jörn Schattenberg and Ian Rowe. In addition to reminiscing about the podcast, Jörn discusses the energy he gets from discussions with colleagues (and from learning interesting things about their lives, like Mazen Noureddin's pro basketball career), while Ian discusses how a surprise in medical school led him to focus much of his research on community-generated data and systems issues. If you enjoy their episodes, you should find this fascinating and fun, all at the same time.
This week's celebration podcast featured interviews including seven of our favorite Surfers. In this week's conversations, we are publishing the interviews in full. Second up: Stephen Harrison and Naim Alkhouri
Louise Campbell and Roger Green interview SurfingNASH co-founder Stephen Harrison and Naim Alkhouri, who Roger describes in this conversation as an "idea fountain." Stephen shares his delight at how this podcast has exceeded his initial expectations, dishes on why the chemistry between the three main Surfers works so well, and tosses out hints for the future. Naim suggests new ideas for programming while telling about the constituency that finds his podcast appearance to be "cool" (HINT: they are little people who live in his house). Amidst the serious content, there are loads of laughs...or maybe it is the other way around. In any case, enjoy!
This week's celebration podcast featured interviews including seven of our favorite Surfers. In this week's conversations, we are publishing the interviews in full. First up: Donna Cryer.
Louise Campbell and Roger Green interview Global Liver Institute President and CEO Donna Cryer about her experiences as regular, guest and back-up MC for the Surfing the NASH Tsunami podcast and, more important, about her mission, her view of the role of Patient Advocate, and how she would like to se the process of study design and selection and the definition of "evidence" become broader and more patient-centric. Sounds serious (it is, sometimes) and visionary (this is Donna, after all), but with plenty of laughter and good spirits all around. Enjoy!
Seven of our favorite Surfers join together to celebrate 20,000 Buzzsprout downloads and our one-year anniversary of moving to Buzzsprout.
Louise Campbell and Roger Green interview Stephen Harrison, Donna Cryer, Naim Alkhouri, Ian Rowe and Jörn Schattenberg to discuss what we have experienced during the first year of SurfingNASH. Each participant reminisces on how they came to the podcast and their favorites memories of the first year, discusses how SurfingNASH brings value to the Fatty Liver community and discussed what they hope to see from the podcast in the year ahead. Equal parts intellectual, warm and funny, this episode will show you sides of the Surfers you haven't seen on earlier episodes, reveals favorite moments and asks some important questions about where Fatty Liver diagnostics and treatment are headed.
Global Liver Institute Founder and CEO Donna Cryer hosts Medidata Vice President Alicia Staley, knowRx co-fonder and Chief Medical Officer Dr. James Powell and Global Liver Institute Director of NASH programs Jeff McIntyre in an eye-opening discussion about what it takes to recruit diverse patients into clinical trials.
The first two conversations in this series focus largely on patients. This one broadens the scope to address what physicians in underserved communities must do to shape a culture of participation and how drug developers and community advocates can support these goals and activities.
Global Liver Institute Founder and CEO Donna Cryer hosts Medidata Vice President Alicia Staley, knowRx co-fonder and Chief Medical Officer Dr. James Powell and Global Liver Institute Director of NASH programs Jeff McIntyre in an eye-opening discussion about what it takes to recruit diverse patients into clinical trials.
In this conversation, the group discusses the importance of building a culture within the patient community that encourages curiosity and interaction by providing sources of information and openness. Listen as these opinion leaders and experts in encouraging broad patient participation describe the principles that underlie their actions.
Global Liver Institute Founder and CEO Donna Cryer hosts Medidata Vice President Alicia Staley, knowRx co-fonder and Chief Medical Officer Dr. James Powell and Global Liver Institute Director of NASH programs Jeff McIntyre in an eye-opening discussion about what it takes to recruit diverse patients into clinical trials.
In this conversation, the group discusses why motivating diverse patient populations is key to creating appropriately diverse clinical trial populations in NASH and NAFLD. Alicia Staley describes her key principles as "collaboration and building collateral." Listen as she and the other panelists discuss actions and programs that are key to success, including a primer on what not to include as patient qualification critera.
Global Liver Institute Founder and CEO Donna Cryer hosts Medidata Vice President Alicia Staley, knowRx co-fonder and Chief Medical Officer Dr. James Powell and Global Liver Institute Director of NASH programs Jeff McIntyre in an eye-opening discussion about what it takes to recruit diverse patients into clinical trials.
The group shares a wealth of goals, actions and the occasional war-story-gone-bad in describing what we all need to do to enroll a diverse set of patients into clinical trials. The keys revolve around information, communication and transparency, but success or failure lie not only in the goals but also in the details. This is one of our most informative episodes on patient recruitment and communication to date.
Jörn Schattenberg and Michelle Long join the Surfers to discuss similarities and differences between the NASH and hypercholesterolemia markets. This conversation focuses on the challenges in communicating the importance of NASH to medical specialties other than hepatology and gastroenterology.
It has been common for industry advocates and financial analysts to discuss the potential for the NASH/NAFLD drug market in comparison to the statin market, but this overlooks differences in the conditions they treat (NASH vs. hypercholesterolemia), the diagnostics available and the health economic environment.
One key difference is that the concept of hypercholesterolemia was straightforward to explain to primary care and the other specialties whose patients exhibited diseases caused by dyslipidemia. This conversation discusses why this kind of communication and education is more challenging in NASH, and also identifies several surprising specialties as important targets for NASH information.
Jörn Schattenberg and Michelle Long join the Surfers to discuss similarities and differences between the NASH and hypercholesterolemia markets. This conversation focuses on the unique challenges posed by the complexity of NASH and NAFLD and the current state of diagnostic testing. It has been common for industry advocates and financial analysts to discuss the potential for the NASH/NAFLD drug market in comparison to the statin market, but this overlooks differences in the conditions they treat (NASH vs. hypercholesterolemia), the diagnostics available and the health economic environment.
It has been common for industry advocates and financial analysts to discuss the potential for the NASH/NAFLD drug market in comparison to the statin market, but this overlooks differences in the conditions they treat (NASH vs. hypercholesterolemia), the diagnostics available and the health economic environment.
In this conversation, panelists discuss how complexities in diagnosing the disease and quantifying its nature and severity in individual patient affect patient treatment today and are likely to affect drug uptake. The group provides a thoughtful look at cholesterol drug use could expand more rapidly than NASH drugs will, even if NASH as broader and more far-reaching impact on population health than cholesterol.
Jörn Schattenberg and Michelle Long join the Surfers to discuss similarities and differences between the NASH and hypercholesterolemia markets. In this conversation, each panelist identifies one significant reason the NASH market will develop differently than statins did.
It has been common for industry advocates and financial analysts to discuss the potential for the NASH/NAFLD drug market in comparison to the statin market, but this overlooks differences in the conditions they treat (NASH vs. hypercholesterolemia), the diagnostics available and the health economic environment.
In this conversation, Roger Green lays out several possible issues, after which panelists Jörn Schattenberg, Stephen Harrison, Michelle Long and Louise Campbell each discuss one difference they consider particularly important. Not surprisingly, answers and perspectives differ between panelists, but all agree that this is a more complex situation than existed with cholesterol 25 years ago.
Jörn Schattenberg and Michelle Long join the Surfers to discuss similarities and differences between the NASH and hypercholesterolemia markets.
It has been common for industry advocates and financial analysts to discuss the potential for the NASH/NAFLD drug market in comparison to the statin market, but this overlooks differences in the conditions they treat (NASH vs. hypercholesterolemia), the diagnostics available and the health economic environment. This episode pinpoints these differences and addresses what they mean in terms of treating the disease and adopting new drugs.
The group covers several important topics very quickly, with focus on pre-launch market development, testing metrics and why it matters which companies are coming to market first. One similarity: in the absence of approved medications, disease treatment rests heavily on improving healthy lifestyles, which is a challenging target no matter the disease.
Quentin Anstee, Louise Campbell, Stephen Harrison, Mazen Noureddin, Ian Rowe and Roger Green convene to review #ILC2021 and share key takeaways and insights. This conversation covers issues around care pathways and treatment roles as NASH becomes recognized as a multidisciplinary health challenge.
The conversation started with a discussion of the attention paid to multi-disciplinary treatment in the #ILC2021 program and evolved into a look at the roles that primary care and different specialties might play in diagnosis, treatment and patient management. While the discussion opened some important topics, it also made clear how much more thinking, planning and educating the Fatty Liver community will need to do if NAFLD and NASH are to receive their proper attention.
Quentin Anstee, Louise Campbell, Stephen Harrison, Mazen Noureddin, Ian Rowe and Roger Green convene to review #ILC2021 and share key takeaways and insights. This conversation covers issues around drug development.
The conversation addressed the various ways that the challenges that the COVID-19 pandemic created for clinical trials in 2020 played out in the drug development presentations at #ILC2021: a higher level of retrospective analysis of earlier trials and relatively few pieces of novel Phase 2b or Phase 3 research adding to knowledge and insight. The group noted that cirrhosis received relatively more attention and even some fresh data as with the efruxifermin late-breaker publication. Finally, the group discussed some of the studies and insights we can expect to see between now and 2022.
Quentin Anstee, Louise Campbell, Stephen Harrison, Mazen Noureddin, Ian Rowe and Roger Green convene to review #ILC2021 and share key takeaways and insights. This conversation covers issues around diagnostics.
The conversation covered several issues relating to use and interpretation of non-invasive testing. Two issues addressed use on NITs in diagnostics and, separately, drug development. A third considered how to develop and support end points generated around non-invasive tests instead of biopsy. In the process, the group discussed the shortcomings of biopsy as a gold standard as well as the practical challenges that keep biopsy in its current place in the hierarchy of test options.
Key opinion leaders Quentin Anstee, Mazen Noureddin and Ian Rowe join Stephen, Louise and Roger to discuss the major lessons and dangling questions from #ILC2021.
The group shares perspectives, insights and questions on four key topics: diagnostics (including both non-invasive technologies and AI/machine learning), drug development, patient populations and policy.Mixed in here you will find discussions on food insecurity, polygenic risk and multi-disciplinary medicine. A great session to hear if you are still organizing your takeaways and questions emerging from the Congress.
Donna Cryer, Vlad Ratziu, Michael Charlton and Mazen Noureddin join Roger Green in reviewing the final day of #ILC 2021.
The conversation revolved around three themes: non-invasive tests as presented at the morning LITMUS session; two promising but incomplete drug trials for a new class of agents and a possible therapy for controlled cirrhotics, and the opportunities and challenges presented by digital meetings (with kudos to EASL for all the platform elements they strengthened from 2020).
Manal Abdelmalek, Ian Rowe and first-timer Ken Cusi join Louise Campbell and Roger Green to review a thought-provoking, assumption-challenging Day Three of #ILC2021.
Most of the presentations the panel covered focused on medications, the core ideas and discussions spoke to changes in thinking. One theme that ran through the discussion was about multi-disciplinary care...and not only because Fatty Liver Endocrinologist Ken Cusi was on the panel. Another was to think about drugs for NASH holistically. In all, this podcast takes the broad view and the long view on treating Fatty Liver diseases, and should provoke new thoughts and ideas in you the listener.
Jörn Schattenberg, Naim Alkhouri, Dr. Michelle Long of Boston University and Livia Alimena of the Global Liver Institute join Roger to review highlights of Day Two at ILC2021.
Each panelist reviewed a favorite presentation of the day, most of which involved learning about the nature of disease through large population analysis. In the course of the discussion, the group discussed lean NASH, COVID-19, food insufficiency, AI and cohort analyses. What did these topics have in common? For one thing, it became clear that we are learning how to think differently about different groups of patients.
Incoming EASL Secretary General Prof. Thomas Berg, Global Liver Institute President and CEO Donna Cryer and Genfit Head of Global Diagnostics Suneil Hosmane share their unique perspectives on Digital ILC 2021 with Roger Green.
In our lead-in episode for #ILC2021, Roger Green conducts interviews with three leaders, each with a unique perspective on what they value about this week's Congress. Incoming EASL Secretary General Prof. Thomas Berg discusses his view on the various ways the Congress will enrich knowledge and interaction in the global Fatty Liver community. Global Liver Institute President and CEO Donna Cryer shares the many ways that ILC has made patients and advocates feel they are welcome at the Congress and capable of making a contribution. Finally, Genfit Head of Global Diagnostics Suneil Hosmane identifies several areas of knowledge that he considers in assessing commercial opportunities. This can serve as a helpful introduction to the Congress or an opportunity to process what you have just seen and learned.
Jörn Schattenberg, Stephen Harrison, Louise Campbell and Roger Green identify specific sessions and presentations they believe will bring the greatest enlightenment around tough challenges and unaddressed issues in Fatty Liver disease.
The topics the Surfers identify vary greatly, from cirrhosis to NITs to public policy issues such as the relationship between food insecurity and NAFLD prevalence. The range of these topics speaks to the breadth and vitality of Digital ILC 2021, as do changes in the digital platform that allow for real-time interactions between attendees.
Stephen Harrison and Jörn Schattenberg discuss what the titles of Digital ILC 2021 presentations tell us about possible findings in drug development.
Drug development presentations will occur throughout Digital ILC 2021, ranging from late-breakers to general session presentations to dedicated sessions. Stephen and Jörn use the titles of presentation to discuss areas of drug development, paying particular attention to treating cirrhosis on one end and drugs that address defatting the liver through metabolic modes of action.
Jörn Schattenberg and the regular Surfers identify one thing about the Digital ILC 2021 meeting they anticipate eagerly and fall into a discussion about pharmacologic and non-pharmacologic approaches to managing metabolic issues.
As the group looked forward to Digital ILC 2021, each panelist identified one source of particular excitement. The answers varied all the way from process (enough time for interaction between speakers) to session themes to individual pieces of content. In the end, discussion of a NAFLD Therapy abstract session served as a springboard to a broader discussion about different ways to reduce or resolve steatohepatitis regardless of effect on fibrosis. The end of the discussion focused on the under-appreciated issue of omega-oil types found in diet.
Joern Schattenberg joins the Surfers to identify exciting presentations and sessions from the Digital ILC 2021 meeting.
Digital ILC 2021 kicks off one week from today, with four days of sessions covering the entire range of liver topics. Professor Schattenberg joins Dr. Stephen Harrison, Louise Campbell and Roger Green in identifying presentations, sessions and major themes they believe will import new knowledge and even change the ways we look at NAFLD and NASH. Want to get revved up for the Congress? Listen here.
Global Liver Institute Director of Global Policy Andrew Scott, Madrigal Pharmaceuticals Co-Founder and CMO Becky Taub, and Central Virginia VA Health Care System Chief of Hepatology and Gastroenterology Dr. Michael Fuchs discuss GLI's US NASH Action Plan and steps different stakeholders can take to support the Plan. In this conversation, the group considers systems issues ranging from commitment to multi-disciplinary approaches to including Fatty Liver metrics in metrics like HEDIS in terms of their ability to focus needed care and attention on NAFLD and NASH.
Michael Fuchs starts by discussing the value of having a multi-disciplinary mission and vision for patient treatment. From there, the group points to several different approaches -- communication, metrics, education -- that will be pivotal to driving that kind of vision and making it effective. In the end, the panelists discuss actions they each can take over the next six months to move us closer to realizing the Action Plan vision.
This conversation is sponsored with a grant from Madrigal Pharmaceuticals. Madrigal Pharmaceuticals is leading the field of NASH therapeutic development with resmetirom, a thyroid receptor beta agonist with potential to address both the liver pathophysiology and fibrosis caused by NASH.
Global Liver Institute Director of Global Policy Andrew Scott, Madrigal Pharmaceuticals Co-Founder and CMO Becky Taub, and Central Virginia VA Health Care System Chief of Hepatology and Gastroenterology Dr. Michael Fuchs discuss GLI's US NASH Action Plan and steps different stakeholders can take to support the Plan. In this conversation, the group discusses the need for common, reliable non-invasive diagnostic tests and education for providers on which tests they should rely on (HINT: not the ones most HCPs are using today!)
All six panelists discuss their own issues surrounding the need for common, reliable diagnostics and a simple way to explain them. Whether it is Becky Taub discussing liver enzyme levels in F2 and F3 patients in clinical trials, Michael Fuchs stating his belief that institutions need to focus more actively on NAFLD and NASH in their screening, or Louise Campbell and Stephen Harrison discussing why we will need better tests and clearer data and messages to motivate patients, all the Surfers agree that diagnostics and triage are key to improving Fatty Liver treatment.
This conversation is sponsored with a grant from Madrigal Pharmaceuticals. Madrigal Pharmaceuticals is leading the field of NASH therapeutic development with resmetirom, a thyroid receptor beta agonist with potential to address both the liver pathophysiology and fibrosis caused by NASH.
Global Liver Institute Director of Global Policy Andrew Scott, Madrigal Pharmaceuticals Co-Founder and CMO Becky Taub, and Central Virginia VA Health Care System Chief of Hepatology and Gastroenterology Dr. Michael Fuchs discuss GLI's US NASH Action Plan and steps different stakeholders can take to support the Plan. In this conversation, Andrew discusses the genesis of the US NASH Action Plan and the group begins to discuss education and awareness opportunities.
Andrew Scott walks a group of engaged stakeholders through Global Liver Institute's reasoning about developing the plan in the first place, the Plan's four key platforms and some early progress with legislation and developing local leaders. The other Surfers ask questions and then begin to share their own perspectives, with Louise Campbell reiterating the vital importance educating families and Stephen Harrison identifying a set of physician targets for NASH education.
This conversation is sponsored by a grant from Madrigal Pharmaceuticals. Madrigal Pharmaceuticals is leading the field of NASH therapeutic
Global Liver Institute Director of Global Policy Andrew Scott walks a diverse set of stakeholders through the US NASH Action Plan, with special focus on education, awareness and clarity in diagnosis and treatment.
In addition to Andrew, Becky Taub, Madrigal Pharmaceuticals co-founder, Director, CMO and President of Research & Development and Dr.Michael Fuchs, Acting Chief of the Division of Gastroenterology and Hepatology and the Central Virginia VA Health Care System, joined Stephen Harrison, Louise Campbell and Roger Green to discuss Global Liver Institute's US NASH Action Plan. Andrew led a discussion of the plan's four major focus areas, while the Surfers and guests discussed what they consider key needs and opportunities in each area.
This episode is sponsored with a grant from Madrigal Pharmaceuticals. Madrigal Pharmaceuticals is leading the field of NASH therapeutic development with resmetirom, a thyroid receptor beta agonist with potential to address both the liver pathophysiology and fibrosis caused by NASH.
EASL Scientific Committee member Luca Valenti joins the Surfers to "crystal ball" potential key outcomes from Digital ILC 2021.
The four panelists each predict one likely outcome from Digital ILC 2021. Interestingly, none of them focus specifically on clinical trials, but instead on a broader range of issues around understanding the metabolic underpinnings of NASH and determining treatment plans and strategy for today, before the new generation of medications arrives.
EASL Scientific Committee member Luca Valenti joins the Surfers to discuss some of the issues that will be discussed at Digital ILC 2021.
After Luca and Stephen Harrison discuss what they consider highlights of this month's Digital ILC meeting, Louise Campbell and Roger Green join them to discuss some of the key issues they anticipate being address at EASL's signature annual event.
Stephen Harrison and EASL Scientific Committee member Luca Valenti Preview Highlights of the Digital ILC 2021.
Luca and Stephen discuss what each of them consider highlights of this month's Digital ILC meeting, focusing not only on presentation and poster topics but also a new meeting platform with improved connectivity. This brief discussion will help you get in the right frame of mind for planning your participation at EASL's signature annual event.
EASL Scientific Organizing Committee member Prof. Luca Valenti joins the Surfers to discuss some of the major NAFLD-related topics we will learn more about at Digital ILC 2021.
This episode begins with the announcement that Surfing the NASH Tsunami is an official Media Partner for Digital ILC 2021! The rest of the episode is devoted to discussing how the meeting came together, some of the major learning opportunities and areas for the meeting, and exciting details on EASL's improved participant platform. Along the way, all four participants describe what they most want to learn about and, more broadly, what they hope will be the Congress's greatest impact on the global Fatty Liver Community.
Global Liver Institute President and CEO Donna Cryer joins the Surfers to discuss International NASH Day 2021. This conversation takes a deeper look at NASH Day and also Global Liver Institute's growth and future plans.
The 4th annual International NASH Day is a major global institution, with endorsements from WHO, EASL, AASLD, at least 14 medical societies, and organizations in at least 26 countries, and more than 100,000 people tuning in at some point during the day. In this conversation, Donna shares her exciting and ambitious future plans for International NASH Day and the Global Liver Institute with the Surfers.
Global Liver Institute President and CEO Donna Cryer joins the Surfers to discuss International NASH Day 2021. This conversation provides and overview of the day's event.
The 4th annual International NASH Day is a major global institution, with endorsements from WHO, EASL, AASLD, at least 14 medical societies, and organizations in at least 26 countries, and more than 100,000 people tuning in at some point during the day. In this conversation, Donna Cryer provides an overview of this year's activities, which are far broader in scope than in previous years. Donna also answers questions from Louise Campbell and Roger Green that serves to demonstrate this event's true global reach.
Roger Green narrates a series of interviews, conversations and viewpoints about NGM Biopharmaceuticals discontinuing its F2/F3 aldafermin program
The SurfingNASH team weaves interviews, conversations and text notes from 9 stakeholders, including US and EU KOLs, program heads, treating physicians, patient advocates and NASH patients into a narrative addressing key issues. Was the ALPINE 2/3 trial a clinical failure? What commercial considerations might have played into NGM BIo's decision? What lessons can we learn about clinical development strategies? NITs vs. biopsy? When to trust headlines and when not. There is a great deal to unpack in a 25-minute episode.
Global Liver Institute President and CEO Donna Cryer joins the Surfers to discuss International NASH Day 2021. Last year's IND had 100+ participants. This year will be bigger! Learn why.
The 4th annual International NASH Day is a major global institution, with endorsements from WHO, EASL, AASLD, at least 14 medical societies, and organizations in at least 26 countries. Global Liver Institute President and CEO Donna Cryer rejoins the Surfers to discuss a day that starts at Midnight in Paris and ends with a gourmet cooking demonstration 18 hours later. This day grows in importance in parallel with GLI, which grows monthly in size and reach. Listen to the episode, catch the enthusiasm.
azen Noureddin returns to discuss the roles different drugs and drug classes will play in NASH therapy after current Phase 2b and Phase 3 candidates have been approved. This conversation considers how the idea that front-line treaters will be PCPs might affect treatment patterns.
This conversation starts with Roger Green pointing out that most real-world patient treatment decisions will be made by front-line, primary care physicians. Stephen Harrison proposes one more application for the "KISS" rule and talks about the role of EHRs in driving long-term guideline development and adherence. Mazen Noureddin considers how order of market entry will affect guideline development and Roger Green discusses other chronic diseases and classes of medication to provide historic context. Like the other conversations from this episode, there is a lot here -- a lot of thoughts, a lot of ideas, a lot of value.
Mazen Noureddin returns to discuss the roles different drugs and drug classes will play in NASH therpy after current Phase 2b and Phase 3 candidates have been approved. This conversation examines the prospect for different kinds of backbone strategies.At one extreme, many chronic therapies have a single monotherapy backbone agent, like what metformin has been to Type 2 diabetes. At the other, there are diseases where prescribers start with multiple different agents, or even different modes of action. The Surfers explore what is likely to happen in the future of NASH: one backbone vs. one for F4 and others for earlier stages vs. the idea that different patients' metabolic issues might suggest different starting points. Louise Campbell goes so far as to ask whether diet and exercise not only should be the starting point but whether it should be taken seriously as a discrete line of therapy. This is an interesting window into our treatment future.
Mazen Noureddin returns to discuss the roles different drugs and drug classes will play in NASH therpy after current Phase 2b and Phase 3 candidates have been approved. This conversation lays out basic premises.In this conversation, Stephen Harrison and Mazen focus on how treatment guidelines and therapeutic choices might vary for patients starting at F2 vs. F3 vs. compensated (maybe even decompensated?) cirrhosis. One key issue is "de-escalation" -- whether guidelines will suggest treating with agents that are more potent injectible anti-fibrotics for later stage patients, then retreating to orals with broader metabolic effects when patients' fibrosis has regressed to F2 or F1. The subject of "backbone therapy" comes up for the first time here, although it will be in later conversations of this episode as well. Louise Campbell and Roger Green round out the conversation with questions and observations. There is a lot to unpack here, so listen, learn and enjoy.
Mazen Noureddin joins the Surfers to explore the issues and needs that will shape treatment guidelines in a world after NASH drugs come to market.
In Season 2 Episode 16, a discussion of cost-effectiveness led to the question, "How will treatment pathways and rules evolve as new NASH drugs come to market." Mazen Noureddin, who raised this issue with Stephen Harrison in the earlier episode, returns to explore the answer ten episodes later.
The discussion considers what the phrase "backbone therapy" will mean in the future of NASH therapy and which agent(s) might attain that status. It considers how treatment models might vary for patients with cirrhosis vs. those with NASH, and for compensated cirrhosis vs. decompensated cirrhosis. It explores the role that AI-driven algorithms powered through electronic records will play in helping primary care physicians, general gastroenterologists and general hepatologists (if there is such a thing) treat patient who might have not only NASH but a range of accompanying metabolic conditions.
This discussion covers a lot of ground in a very short time. It stimulates and challenges. Enjoy it!
(This episode has been reposted to include the complete conversation content.)
Louise Campbell and Roger Green join co-authors Stephen Harrison, Naim Alkhouri and first-time guest Prof. Samer Gowrieh to discuss why this epidemiology paper from the 2021 Journal of Hepatology is an urgent call to action on NAFLD and NASH screening and treatment.
Considered in its totality, the data emerging from the 2021 Journal of Hepatology paper "Prospective evaluation of the prevalence of non-alcoholic fatty liver disease and steatohepatitis in a large middle-aged US cohort" come across as a clarion call to screen unaware, asymptomatic patients more aggressively and treat them more intently, even before we have new, approved medications in market. Whether you are familiar with the paper or not, you will want to hear why the panelists consider this data so compelling and the call to action so urgent.
(**This episode has been reposted to include the complete conversation content.)
Louise Campbell and Roger Green join co-authors Stephen Harrison, Naim Alkhouri and first-time guest Prof. Samer Gowrieh to dive deeper into key findings from the 2021 Journal of Hepatology paper titled "Prospective evaluation of the prevalence of non-alcoholic fatty liver disease and steatohepatitis in a large middle-aged US cohort."**
A deeper dive into the data coming from the 2021 Journal of Hepatology paper "Prospective evaluation of the prevalence of non-alcoholic fatty liver disease and steatohepatitis in a large middle-aged US cohort" reveals several troubling trends, including percentages of patients with F2/F3 NASH increasing far faster than the overall NAFLD growth rate and population subgroups in which a majority of the study patients exhibited NAFLD and over one in three exhibited NASH. Whether you are familiar with the paper or not, you will want to listen to this conversation to hear points you might have missed.
(This episode has been reposted to include the complete conversation content.)
Stephen Harrison, Naim Alkhouri and first-time guest Prof. Samer Gowrieh share key findings from their 20210 Journal of Hepatology paper titled "Prospective evaluation of the prevalence of non-alcoholic fatty liver disease and steatohepatitis in a large middle-aged US cohort."The 2021 Journal of Hepatology paper "Prospective evaluation of the prevalence of non-alcoholic fatty liver disease and steatohepatitis in a large middle-aged US cohort" is the largest prospective study to estimate NAFLD and NASH prevalence in an asymptomatic population with 664 patients evaluated. In this conversation, three of the paper's co-authors discuss the reasons for conducting this study, the methodology they designed and some key results. They paint a stark picture of a disease with far greater frequency and severity than currently accepted data suggest.
Study co-authors Stephen Harrison, Naim Alkhouri and Samer Gawrieh suggest that current estimates of NAFLD and NASH populations in the US may be meaningfully understated.Earlier this year, Drs. Harrison, Alkhouri, Gawrieh and seven co-authored published a paper in the Journal of Hepatology titled, "Prospective evaluation of the prevalence of non-alcoholic fatty liver disease and steatohepatitis in a large middle-aged US cohort." This study of 664 non-symptomatic patients revealed a 38% incidence of NAFLDand 14% incidence of NASH. While there were no cases of cirrhosis, 5.9% of patients demonstrated biopsy-diagnosed F2 or F3 NASH. Incidences were higher in several subgroups, notably including patients with Type 2 diabetes or obesity and Hispanic patients.
The three co-authors discuss the motivation to do this study, methods they used and key findings. More gripping were their discussion of implications and the things that surprised them. Louise Campbell and Roger Green asked more questions about the NAFLD and NASH incidence numbers, contrasted them to other US estimates and tied them to other ex-US patient populations.
The group consensus is that this issue is more pressing and prevalent than is generally reported, and that the effects of COVID-19 should make the challenge larger. This episode is a call to action to think more creatively and urgently about treating Fatty Liver disease.
After having time to think, six of the panelists who covered sessions at the Fourth Global NASH Congress get together one more time to conisder key takeaways from the Congress. This conversation is organized around competing strategies for diagnostic testing as the NASH market evolves.
After hearing presentations from 43 speakers at the Fourth Global NASH Congress, six SurfingNASH panelists convene once more to debate how the diagnostics market will develop. With a profusion of options, physicians, payers and regulators will have decisions ahead. There is some disagreement on the year in which events will happen, but not on the basic pattern of market evolution.
After having time to think, six of the panelists who covered sessions at the Fourth Global NASH Congress get together one more time to consider key takeaways from the Congress. This conversation is organized around adoption of non-invasive testing in clinical development and when drugs will come to market.
After hearing presentations from 43 speakers at the Fourth Global NASH Congress, six SurfingNASH panelists convene once more to debate how long it will take before we have new medicines to use in identifying and treating patients. This is related to the question of when FDA and EMEA will accept non-invasive tests in pivotal trials. There was some disagreement on the year in which events will happen, but not on the basic pattern of market evolution.
After having time to think, six of the panelists who covered sessions at the Fourth Global NASH Congress get together one more time to consider key takeaways from the Congress. This conversation is organized around changes in treatment paradigms and guidelines.
After hearing presentations from 43 speakers at the Fourth Global NASH Congress, six SurfingNASH panelists convene once more to consider how treatment paradigms and guidelines are likely to evolve over the next five years. This discussion focuses on general themes and differences between the US and UK market evolution. The conversation includes controversy and probing questions, all with laugher and camaraderie.
The SurfingNASH coverage team from the Fourth Global NASH Congress convenes one more time to consider key takeaways from the Congress. Manal Abdelbalek, Naim Alkhouri, Ian Rowe, Suneil Hosmane, Louise Campbell and Roger Green all share high points, opportunities and lingering questions.On April 28 and 29, 2021, over 175 Fatty Liver stakeholders from across the globe convened virtually for the Fourth Global NASH Congress, and Surfing the NASH Tsunami was there to hear each of 43 speakers and share highlights with our listeners. Now that the Congress has ended and everyone has had time to reflect, the coverage team convenes one more time to consider the implications of what we heard about diagnostics, drugs, non-pharmacological interventions and changing paradigms. This discussion includes controversy and probing questions, all with laughter and camaraderie.
The SurfingNASH Team has curated over three hours of recordings from the Fourth Global NASH Congress to highlight pieces that discuss the current and future states of diagnostics in Fatty Liver disease. You will hear Manal Abdelmalek, Naim Alkhouri, Suneil Hosmane, Ian Rowe, Jörn Schattenberg, Louise Campbell and Roger Green sharing opinions and debating issues.Discussions about diagnostics ran through SurfingNASH's entire coverage of the Fourth Global NASH Congress. Listen here for some of the diagnostics highlights. The group discusses exciting new precision diagnostics, urine and breath-based biopsies, realistic expectations for diagnostics in market today and implications for clinical trials and patient treatment and other related questions in a fast-moving set of pieces.
Ian Rowe and GenFit Global Diagnostics Leader Suneil Hosmane join Louise and Roger as they keep discussing Day Two of the 4th Global NASH Congress.On April 29, over 175 NASH stakeholders from across the globe met virtually to hear 20 presentations from leaders in academia and industry. SurfingNASH selected 9 presentations to discuss in a session recorded right after the conference concluded. When the five panelists got together, the discussion extended to 90 minutes...too long for a single episode.
Episode 23 features Suneil Hosmane discussing lifestyle and exercise, Ian Rowe discuss public policy in the US Veterans Health system, and Ian and Roger Green reviewing three developmental drugs discussions from the conference. Louise Campbell lends perspective throughout. Stimulating...engaging..."can't miss."
Naim Alkhouri, Ian Rowe and GenFit Global Diagnostics Leader Suneil Hosmane join Louise Campbell and Roger Green to review presentations from Day Two at the 4th Global NASH Congress.On April 29, over 175 NASH stakeholders from across the globe met virtually to hear 20 presentations from leaders in academia and industry. SurfingNASH selected 9 presentations to discuss in a session recorded right after the conference concluded. When the five panelists got together, the discussion extended to 90 minutes...too long for a single episode.
Episode 22 features Naim Alkhouri and Louise Campbell discussing featured presentations on genomics, transcriptomics and the genetics of precision medicine, plus a review of belapectin and non-hepatologist awareness of and commitment to treat NASH and NAFLD. The conversation features deep dives into drug development and debates on the proper public health strategy for treating NAFLD patients. Stimulating...engaging..."can't miss."
HEP Dynamics will publish the rest of the Day Two reviews in Episode 23 on Saturday, May 1.
Manal Abdelmalek, Jörn Schattenberg and GenFit Global Diagnostics Leader Suneil Hosmane join the Surfers to review presentations from Day One at the 4th Global NASH Congress.On April 28, over 175 NASH stakeholders from across the globe will meet virtually to hear 23 presentations from leaders in academia and industry. SurfingNASH has selected 11 presentations to discuss in a session we will record right after the conference concludes. The speakers and their broad topic areas are:
Manal Abdelmalek -- innovative non-invasive non-device diagnostics
Jörn Schattenberg -- Developmental drugs that address fructose metabolism
Suneil Hosmane -- Leading edge diagnostic strategies and agents in development
Louise Campbell -- Challenges in using and assessing non-invasive diagnostics in initial diagnosis and secondary/tertiary patient care
Roger Green -- Regulatory perspectives
The Surfers explore the impact that NASHmap, the first Machine Learning model that can identify patients likely to have NASH, can have on clinical trials and patient treatment.Prof. Schattenberg and colleagues built the NASHmap model from a NIDDK database and validated it using the Optum de-identified EHR dataset. The model includes 14 variables, some obvious, others less so, that produce an AUC of 0.82 in the NIDDK database and 0.79 in the Optum database. This conversation explores NASHmap's powerful implications for future clinical trial recruitment and large-scale patient screening.
The Surfers analyze outputs from NASHmap, the first Machine Learning model that can identify patients likely to have NASH, to learn what we can about the disease and how to think about its value for racial and ethnic minorities.
Prof. Schattenberg and colleagues built the NASHmap model from a NIDDK database and validated it using the Optum de-identified EHR dataset. The model includes 14 variables, some obvious, others less so, that produce an AUC of 0.82 in the NIDDK database and 0.79 in the Optum database. This conversation explores some model elements and statistical outputs to glean knowledge about what the model says about NASH itself.
Jörn Schattenberg discusses NASHmap, the first Machine Learning model that can identify patients likely to have NASH in clinical settings. Louise, Roger and guest Dr. Kris Kowdley join Jörn to discuss the model from academic, patient treatment and statistical perspectives.
Prof. Schattenberg and colleagues built the NASHmap model from a NIDDK database and validated it using the Optum de-identified EHR dataset. The model includes 14 variables, some obvious, others less so, that produce an AUC of 0.82 in the NIDDK database and 0.79 in the Optum database. The episode focuses on how the model was built and what it implies for clinical trial recruitment, patient care and the view it provides of NASH risk factors. This has powerful implications for future clinical trial recruitment and large-scale patient screening.
Jörn Schattenberg discusses the issues that drove the project to develop a Machine Learning model that can identify patients likely to have NASH in clinical settings, and discusses key elements of study and model design.Prof. Schattenberg and colleagues built the NASHmap model from a NIDDK database and validated it using the Optum de-identified EHR dataset. The model includes 14 variables, some obvious, others less so, that produce an AUC of 0.82 in the NIDDK database and 0.79 in the Optum database. This conversation focuses on why the collaborators undertook this project and how the model was built.
Jörn Schattenberg and GenFit Global Diagnostics Leader Suneil Hosmane join the Surfers to review pharmacotherapy themes to be covered at the 4th Global NASH Congress.Keynote Speaker Suneil Hosmane joins Louise Campbell and Roger Green to form the coverage team for the 4th Global NASH Congress. In this conversation, Jörn Schattenberg joins them to review drug-related topics covered at the Congress. This conversation discusses issues ranging from modes of action that attack fructose metabolism to the importance of hearing regulators at meetings like this one. Listen to get a feel for what commercial, financial and R & D actors can hear about by attending the event on April 28 and 29.
Jörn Schattenberg and GenFit Global Diagnostics Leader Suneil Hosmane join the Surfers to review holistic and patient-centric issues to be covered at the 4th Global NASH Congress.Keynote Speaker Suneil Hosmane joins Louise Campbell and Roger Green to form the coverage team for the 4th Global NASH Congress. In this conversation, Jörn Schattenberg joins them to review patient-centric topics covered at the Congress. This conversation discusses the increasing imoportance of phenotyping in diagnosing and prescribing for individual patients after drugs are available. Listen to get a feel for what commercial, financial and R & D actors can hear about by attending the event on April 28 and 29.
Jörn Schattenberg and GenFit Global Diagnostics Leader Suneil Hosmane join the Surfers to review non-invasive testing themes to be covered at the 4th Global NASH Congress.
Keynote Speaker Suneil Hosmane joins Louise Campbell and Roger Green to form the coverage team for the 4th Global NASH Congress. In this conversation, Jörn Schattenberg joins them to review non-invasive testing topics covered at the Congress. This conversation discusses advances in technology and the need for non-invasive tests that provide stronger positive predictive value. Listen to get a feel for what commercial, financial and R & D actors can hear about by attending the event on April 28 and 29.
Jörn Schattenberg and GenFit Global Diagnostics Leader Suneil Hosmane join the Surfers to survey the agenda for the 4th Global NASH Congress.
The 4th Global NASH Congress has presentations of interest on a broad array of topics. Congress Keynote Speaker Suneil Hosmane joins Louise Campbell and Roger Green to form the coverage team for this event. Along with Jörn Schattenberg, they review the topics of interest at the Congress and highlight some papers and topics that SurfingNASH will cover in its end-of-day episodes on April 28 and 29. Listen to get a feel for what makes this a worthwhile Congress for commercial, financial and R & D actors needing to stay up-to-date on the latest trends and insights.
Roger Green conducts one-on-one interviews with Stephen Harrison and Alina Allen to explore specific issues regarding new issues and insights for clinical research and drug development resulting from the work of Dr. Allen and her colleagues.Stephen Harrison discusses the important contribution this paper makes to our knowledge about disease progression. He then suggests several types of studies and issues that are likely to progress from this research and closes by focusing on its immense value for cirrhotic patients and medications. Alina Allen discusses her vision of how both research and treatment might evolve as researchers learn more about the interplay of different types of diagnostic testing in both research and clinical settings.
The group focuses on the patient treatment implications of being able to identify the patients who are at risk of rapid progression, particularly among those with compensated cirrhosis.
Louise Campbell and Alina Allen discuss the psychological and practical aspects of treating patients (particularly those with cirrhosis) who know they are risk of imminent disease progression, while Roger Green asks whether this kind of predictive power might drive Compassionate Use protocols for agents that have not yet been approved. The question, "Who Will Be the Larry Kramer of NASH?" comes into this discussion as well.
Alina Allen shares the results of her recent Clinical Gastroenterology and Hepatology paper on predictive value of MR Elastography in determining likelihood of progress for NASH patients exhibiting F1 - F3 disease and separately, those living with cirrhosis.
Using a longitudinal data base of over 800 patients spanning 12 years, Dr. Allen and her colleagues published analysis demonstrated that kPa readings based on MR Elastography produced highly significant results predicting likelihood of progression. Alina shares some of the thinking that drove the desire to do the study and presents some of the key results. Louise Campbell and Roger Green ask clarifying questions from their own very distinct perspectives.
Alina Allen of the Mayo Clinic joins the Surfers to discuss her recent publication demonstrating that kPa scores from MR Elastography can predict the course of disease for non-cirrhotic and cirrhotic patients and consider its implications for clinical trials and every day patient treatment.
This episode has an unusual format. First, Alina Allen discusses her study and its implications with Louise Campbell and Roger Green. Next, Roger interviews Stephen Harrison on what he considers most important about the study and any comments on the transcript. Finally, Roger and Alina explore one remaining issue.
What emerges is an understanding that the importance of shifting from what Alina calls the "box" of looking for a fixed relationship between fibrosis levels and kPa scores to defining a linear relationship. The linear relationship simultaneously creates multiple questions for academic reason and provides a simple way for the clinician to inform the patient about level of risk therapeutic options and next decisions. This is an exciting, vitally important shift both in trials and the clinic.
Ian Rowe presents more findings from his work in Leeds, revealing paradoxes and complexity in the patient screening process. This conversations starts by questioning the incremental value of ultrasound in the diagnostic process and proceeds to consider the goals of screening and two specific challenges.
This conversation focuses on how to improve diagnostic accuracy and speed, starting with the question of how often ultrasound contributes to a more robust diagnosis than a provider would come to without it. From there, the conversation shifts to two critical issues: how should we consider test development and use given how often testing produces indeterminate results, and are we considering the value of a test not only in terms of screening but also imparting information that motivates patients to manage themselves better. Louise closes this conversation with an impassioned way to use tests to educate patients and, at the same time, ensure that the system gets the right patient to the hepatologist and the right treatment to patients who might need to get there.
Ian Rowe presents more findings from his work in Leeds, revealing paradoxes and complexity in the patient screening process. Listen to this conversations to consider the goals for a therapy that, in Ian's words, "treats the patient and not the NASH."Ian Rowe and colleagues have created a model to assess the tradeoff of liver risk reduction vs. CVD risk reduction at different levels of fibrosis and age. The model suggests that for F2 and F3 patients, the cardiovascular profile of a medication may have greater effect on overall morbidity and mortality than the liver profile, even if the drug produces significant liver improvements. The model and its outputs are enlightening, the questions it raises are clinically important. Stephen Harrison shares some recently available data on efruxifermin that suggests a positive effect for compensated cirrhotics, and questions what a drug must do to make sense for earlier stage patients.
Ian Rowe presents more findings from his work in Leeds, revealing paradoxes and complexity in the patient screening process. Listen to this conversation to consider what "efficiency" means in the context of patient diagnosis and whether "less expensive" is always more efficient.In this conversation, he questions whether positioning a second blood-based test between FIB-4 and FibroScan improves cost-effectiveness or, simple diagnosis. One Spoiler Alert: The Leeds data suggests that efficient screening processes for NAFLD and alcoholic liver disease may differ significantly. Stephen Harrison notes that polygenetic testing will introduce an entirely new set of issues to this question. There's a lot to consider here...
Ian Rowe joins the Surfers to discuss more detailed findings from the on-going analyses he and Richard Parker are conducting on abnormal liver tests among patients in Leeds, UK.In this episode, Ian discusses three specific findings that seem paradoxical but make complete sense. As Stephen points out several time over the course of the episode, this work demonstrates how complicated and challenging it it to find the fastest, most streamlined way to get each patient to the right diagnosis. Coupled with Mazen Noureddin's discussion in Episode 16, these two discussions demonstrate the value of non-invasive tests compared to biopsy while also demonstrating the tremendous room for growth in non-invasive testing, both in making better use of the tests we have and also developed better tests than those that exist today.
The final conversation of Episode 16 explores possible possible pathways and treatment strategies for NASH therapy in a future world with multiple classes of agents.
In different ways, Mazen Noureddin and each Surfer discuss how cost-effective patient treatment might actually provide the right medicine for the right patient all along the therapeutic path.
What makes NASH a little different from other diseases? Because the liver can heal itself, doctors will need to manage drug use during the disease regression process if all goes well.
This is a different way of thinking, driven in part by the ground-breaking cost-effectiveness work Mazen and others have brought forward.
Mazen Noureddin and Stephen Harrison discuss future directions cost-effectiveness research in and outside the U.S. might take, while the Surfers consider the implications.
In response to questions from Roger Green and Stephen Harrison, this conversation starts by exploring where cost-effectiveness research might head next. Louise Campbell provides context from other recent studies and Stephen asks about the impact of expanding these models to encompass costs of hepatocellular carcinoma. At the end of this conversation, the group considers how public explanation of expanded testing might sit with patients and other stakeholders.
Mazen Noureddin describes how he became engaged in studying the cost-effectiveness of widespread NASH screening for diabetics in the US, and what he has found, while the Surfers comment on the value of this pivotal work.
After Mazen discusses how he became engaged in studying cost effectiveness in screening diabetes patients for NASH, he offers a 30,000-foot view of his findings and shares thoughts on what he plans to study next.
Stephen Harrison and Louise Campbell comment on the exceptional value of his work, after which Roger Green joins Louise in asking how COVID-19 might shape future cost effectiveness estimates.
This ground-breaking work has the potential to expand and redefine the role of population testing in the coming Fatty Liver pandemic.
**Mazen Noureddin joins the Surfers to discuss his work determining cost effectiveness of Non-Invasive Testing in Type 2 diabetics and the broader population. The discussion shifts to considering broader treatment issues.
Dr. Noureddin starts the discussion by providing a history of cost-effectiveness research in NASH and NAFLD. At a population level, biopsy turns out never to be cost-effective while less expensive tests almost always are. As the group brainstormed implications and new questions, they touched on theories on how cost-effectiveness for F3 and F2 patients might differ, and even how chronic therapies and sequential use of specific medicines might reflect cost-effectiveness issues. An enlightening way to think about testing and treatment today, and how these will evolve over time.**
Surfing the NASH Tsunami closes the book on NASH-TAG 2021 by considering highlights and major themes of the conference. The conversation focuses on the dramatic increase in disease knowledge and drug development over the past year and highlights some specific papers and ideas. A thoughtful, energetic conclusion to a meeting that left much to think about and many reasons to be excited.NASH-TAG co-director Vlad Ratziu and Global Liver Institute President/CEO Donna Cryer join the Surfers to review high points of the conference. The discussion ranges from the reasons that NASH-TAG is so special to the implications of increasing disease knowledge Along the way, the group pays significant attention to the growing knowledge about non-invasive clinical testing, the value that an array of drugs with different modes of action are proceeding toward clinical success and eventually treatment of large numbers of patients. In addition to adding to the substantive conversation, co-directors Vlad Ratziu and Stephen Harrison discuss how specific elements of conference design lend to integrated thinking and thoughtful analysis of complex phenomena. This is a fitting wrap-up for a fantastic conference.
Naim Alkhouri and Jörn Schattenberg join Roger and Donna to review the closing session of NASH-TAG 2021, a potpourri of basic science and review of promising drugs earlier in development.
The Saturday afternoon closing session of NASH-TAG 2021 spends half its time discussing basic science issues and the other half with BioPharma company drug developers discussing their promising drugs in development. Last year, this session yielded some real fireworks! On Sunday, join SurfingNASH to sort out how what the data means, how the pieces fit together and what questions will require more exploration. If you send us any questions emerging from Session #4 or the podcast, we will review them in our NASH-TAG wrap-up episode next week.
NASH-TAG Co-director Michael Charlton and Ian Rowe join Roger, Louise and Donna to review the morning that Michael himself identified as one of two highlight sessions of NASH-TAG 2021.The Saturday morning session of NASH-TAG 2021 envisions a world of clinical trials without biopsies, considers implications of enrolling co-morbid and other challenging patients, ands winds up with a debate about the role of diabetes drugs in the future of NASH therapies. After the session, join SurfingNASH to sort out how what the data means, how the pieces fit together and what questions will require more exploration. If you send us any questions emerging from Session #3 or the podcast, we will review them in later NASH-TAG episodes and try to get feedback from those at the meeting.
Jörn Schattenberg and Naim Alkhouri join the Surfers (including NASH-TAG co-director Stephen Harrison) to review NASH-TAG session to with its focus on innovative trial design and improving histological analyses.The Friday afternoon session of NASH-TAG 2021 highlights innovation in clinical trial design and histologic analysis. Before NASH-TAG starts its Day Two, join SurfingNASH to sort out how what the data means, how the pieces fit together and what questions will require more exploration. If you send us any questions emerging from Session #2 or the podcast, we will review them in later NASH-TAG episodes and try to get feedback from those at the meeting.
Manal Abdelmalek and Ian Rowe join Roger, Louise and Donna to review the morning that Vlad Ratziu and Michael Charlton both identified as the highlight session of NASH-TAG 2021.
The Friday morning session of NASH-TAG 2021 highlights advancing research for five major NASH drugs in development, explores the question why drug trials fail and wraps up with a rapid-fire session on promising data. Surfers were excited about some of the new drugs and found the presentations from Vlad Ratziu and Mary Rinella about why cirrhotic and non-cirrhotic drug trials fail to be particularly powerful and well-presented.
After the session, join SurfingNASH to sort out how what the data means, how the pieces fit together and what questions will require more exploration. If you send us any questions emerging from Session #1 or the podcast, we will try to review them during later NASH-TAG episodes.
NASH-TAG Co-directors Vlad Ratziu and Michael Charlton talk with Roger Green about the upcoming conference, after which Roger discusses the SurfingNASH coverage plan for NASH-TAG.
If you listen to SurfingNASH, you already know exactly how Stephen Harrison feels about NASH-TAG and what lights him up about this year's agenda. Now, listen as two other co-directors, Vlad Ratziu and Michael Charlton, discuss how the meeting started, what makes it special and what they are looking forward to most in this year's event as they speak with Roger Green.
Afterwards, Roger announces the SurfingNASH coverage plan for NASH-TAG, includes dates and times, guests and basic focus. If you plan to attend virtual NASH-TAG, this episode will provide invaluable insight and information before you arrive.
Donna Cryer joins the Surfers to consider some of the public health issues and implications surrounding treatment of Early Fatty Liver disease and related metabolic diseases. EXTRA: Louise Campbell discusses her public health-driven motivation to form Tawazun Health.
This episode is sponsored by Echosens. Echosens is partnering with Chronwell and ModifyHealth to offer LIVErHEALTHY, an integrated program of non-invasive monitoring, technology-supported behavior support, nutritional counseling and delivery of medically-tailored meals.
After focusing solely on identify and motivation, the Surfers switch focus to consider public health issues. Donna Cryer discusses specific challenges linked to diet and education that Public Health could address better. Louise Campbell describes her motivation in forming Tawazun Health to provide education and feedback for those who lacked the insight necessary to take better care of themselves, while Stephen Harrison links these issues to how he treats patients today.
Donna Cryer and Roger Green lead a conversation of why identity matters for patients trying to resolve fatty liver disease without medication, while Stephen Harrison and Louise Campbell discuss some of their methods for doing so.
This episode is sponsored by Echosens. Echosens is partnering with Chronwell and ModifyHealth to offer LIVErHEALTHY, an integrated program of non-invasive monitoring, technology-supported behavior support, nutritional counseling and delivery of medically-tailored meals.
In this conversation, the group discusses ways that patient identify is pivotal in success. Roger Green and Donna Cryer discuss the "Why", while Stephen Harrison and Louise Campbell rely on their own experiences as healthcare providers to discuss the "how" -- methods that work for them. In the end, the key point is that it is not enough for a patient to want to lose weight, de-fat their livers, or simply get their HbA1c levels down. The key is for patients to change the way they look at themselves and the role of health in their lives.
Executives from Echosens, Chronwell and ModifyHealth join to introduce LIVErHEALTHY, their integrated program for early Fatty Liver disease that integrates non-invasive monitoring, technology-supported behavior support, nutritional counseling and delivery of medically-tailored meals.
This episode is sponsored by Echosens. to introduce LIVErHEALTHY. Echosens is partnering with Chronwell and ModifyHealth to offer LIVErHEALTHY, an integrated program of non-invasive monitoring, technology-supported behavior support, nutritional counseling and delivery of medically-tailored meals.
In this conversation, our sponsors introduce the LIVErHEALTHY program. First Dr. Juan Pablo Frías discusses why behavioral, lifestyle and diet interventions are so important in treating obesity and NASH patients. When Dr. Frías has finished, executives of the three LIVErHEALTHY partners each present the services they are offering through the program. Finally, Global Liver Institute President and CEO Donna Cryer and Dr. Mazen Nooureddin of Cedars Sinai in Los Angeles, CA join host Roger Green to ask several questions about the LIVErHEALTHY program. LIVErHEALTHY is an innovative, broad-spectrum approach that physicians can offer to obesity and NASH patients. You will want to learn about this program as something doctors can offer patients today as well as a platform for things to come.
Donna Cryer joins the Surfers to discuss the importance of identity in lifestyle modification, after which our sponsors from Echosens present LIVErHEALTHY, a program that combines non-invasive testing, technology-enabled behavior support and a food and nutrition element.
Over the past two weeks, we have discussed the idea that diagnostic development in Fatty Liver Disease are progressing faster than medication. This episode looks at the issue of non-pharmacologic therapy from two points of view. First, Donna Cryer joins the Surfers to consider the role identity and self-definition play in the patient's ability to integrate healthy diet and exercise habits into lifestyle. After this, our sponsors from Echosens are joined with their collaborators from Chronwell and ModifyHealth to present LIVErHEALTHY, a multifactorial program that combines non-invasive testing, technology-assisted behavioral support, nutritional counseling and delivery of healthy meals. LIVErHEALTHY will support patients seeking a healthier lifestyle to help them address fatty liver and related metabolic conditions like obesity and diabetes. Mazen Noureddin joins Donna and Roger to ask questions about this innovative pilot program. There is much to ponder and learn in this session.
This conversation integrates two significant side conversations during the review of the NASH-TAG 2021 agenda, one about creativity and intellectual ferment and the other about what we can learn from COVID-19 about how to motivate patients.
While reviewing the NASH-TAG 2021 agenda, the group digressed several times. This conversation incorporates the two most interesting. In the first, Stephen Harrison discusses how this meeting design drives creativity and intellectual ferment and the other Surfers comment. In the second, Stephen poses a question to Louise Campbell about what patient motivation to take the COVID-19 vaccine can teach us about selling NASH patients on the benefits of weight loss. This conversation exemplifies how the NASH-TAG approach and design fosters innovative thinking and excellent networking...a good motivation to register for virtual NASH-TAG at https://www.nash-tag.org/.
Stephen Harrison previews Day Two of NASH-TAG while Ian Rowe, Louise Campbell, and Roger Green the issues that each of them anticipates most eagerly.
Stephen Harrison previews the second-day agenda for NASH-TAG 2021, with a diverse set of innovative and challenging topics. Louise Campbell, Ian Rowe, and Roger Green each identify a different discussion they will be most excited to hear. This is an animated conversation and good motivation to register for virtual NASH-TAG at https://www.nash-tag.org/.
Stephen Harrison discusses the history of NASH-TAG and what makes it special while previewing Day One of the 2021 meeting.
In this conversation, Stephen Harrison and Roger Green share their views of what makes NASH-TAG a special event, after which Stephen reviews the Day One agenda, focusing on elements he considers particularly exciting. Louise Campbell and Ian Rowe share what they value most from their own, unique perspectives. This is a great conversation, and excellent motivation to register for virtual NASH-TAG at https://www.nash-tag.org/.
Stephen Harrison previews NASH-TAG 2021, the pre-eminent NASH drug development meeting, which will take place from March 10-12.
This year marks the 5th annual NASH-TAG, a meeting focused solely on NASH drug and diagnostics development. The NASH-TAG format calls for "deep dives" into key issues and combines innovative presentation formats with debates on pivotal issues. Stephen Harrison walks Louise, Roger, and our guest Ian Rowe through the agenda. The panelists raise provocative questions about the agenda, and wander into informative conversations about how knowledge develops and how responses to the COVID-19 vaccine may prove instructive in motivating patients. Lots to think about here...and good motivation to register for virtual NASH-TAG.
The panelists consider the barriers to bringing NASH into central consciousness in diabetes therapy and some keys to success.
Louise Campbell and Roger Green discuss issues and challenges in educating diabetic patients about NAFLD and NASH. Louise discusses how the rising amount of mortality tied to liver cancer should create a new urgency to broaden focus about the role the liver plays in metabolic health. Roger raises the role that reference labs like Quest and LabCorp have played in driving awareness of underappreciated diseases. The group has several ideas and avenues to explore. Listeners take heed...we have much to figure out and do.
Wayne Eskridge describes some of the opportunities and concerns that affect diabetic patients might experience as they learn about NASH and the liver issues related to diabetes.Patient, patient advocate and Fatty Liver Foundation Wayne Eskridge considers ways that diabetic patients might respond to the joint ideas that they have fatty liver issues and that some diabetes drugs might treat them. He considers issues of information overload and education and the pivotal role physician advocacy plays in driving that education. The other panelists discuss the need for multiple specialties to collaborate in educating patients and providing a more holistic view of how metabolic diseases interact to damage patient health.
Jörn Schattenberg reviews modes of action for GLP-1 agonists and SGLT-2 inhibitors and discusses the data that exist in NAFLD and NASH.
The group considers scientific issues surrounding the newer diabetes drugs. First, Jörn Schattenberg presented mode-of-action and research data on the two classes of drugs. After this, Wayne Eskridge asked questions from the patient perspective, Louise Campbell explores issues from a holistic perspective and Roger Green raised data points and concepts that arose in earlier episodes of the podcast.
Jörn Schattenberg and Fatty Liver Foundation President Wayne Eskridge join Louise and Roger to consider the current and future roles that GLP-1 receptor agonists like semaglutide and SGLT-2 inhibitors like Jardiance in treating NASH patients.
Over the next couple of years, we are likely to see improvements in our ability to diagnose and track NASH patients but no new medicines to treat them. On this podcast, Jörn Schattenberg reviews data on the role that two relatively recent classes of diabetes drugs, GLP-1s (semaglutide) and SGLT-2s (Jardiance), can play in NASH and NAFLD therapy. Wayne Eskridge discusses implications for patients. while Louise Campbell and Roger Green elaborate opportunities and challenges in educating patients and health care professionals to think about liver and diabetes in a more integrated way. This episode presents perspectives and concepts with value today.
Three experience NASH trial site execs identify at least 11 specific things to consider when designing your trial protocols.
Stephen Harrison challenges colleagues Naim Alkhouri and Rashmee Patil to identify a "Top Ten" of criteria to consider/pressure test in designing protocols...and they come up with at least 11!
In the end, Naim Alkhouri advocates for sponsors talking to trial sites, not simply CROs, during the design phase.
Rashmee Patil highlights the importance of educating patients and Stephen Harrison returns to the idea of designing trials that are "Good, not great". There is a wealth of information to unpack and absorb here.
The panel explores three less obvious ways that the COVID-19 pandemic has affected the ability to recruit the right patients into clinical trials.
This week, SurfingNASH discusses why recruiting and maintaining the right patients for NASH clinical trials will require focus, discipline, and perhaps a new way of thinking about trial recruitment.
When we think of how COVID-19 has reshaped medicine, we usually think about patient fear and the impact of staff exposure. Through the recruitment window, the issues change. Recruitment becomes more challenging because (a) patient-physician communication has declined in frequency and mostly been via video; (b() physician-physician education has fallen prey to tighter schedules, larger patient workloads, and inability to meet due to social distancing; and (c) physicians whose schedules are jammed with more patients and constrained to what they can achieve in telehealth visits have less time and energy to think "outside the box" and explore new areas. Listen to hear a more graphic picture of how these phenomena interact and amplify.
Naim Alkhouri and Dr. Rashmee Patil of the South Texas Research Institute join the Surfers to discuss misconceptions about the ease of recruiting and qualifying patients for NASH clinical trials.
Exciting Phase 2b results over the last few months will increase demand for patients to include in NASH clinical trials. So will the recent FDA white paper and webcast, which focused on larger populations for safety evaluation. This week, SurfingNASH discusses why finding these patients will require focus, discipline and perhaps a new way of thinking about trial recruitment.
Drs. Naim Alkhouri and Rashmee Patil join the Surfers to explore this issue. This section explores the reasons it is fallacy to believe there are "plenty of patients" to fill clinical trial slots. Naim, Rashmee and Stephen (all of whom are intimately engaged in patient recruitment for NASH trials) explain the process whereby a high-performing center can screen 10,000 patients in a year and find 150 (best case) who will qualify. A fast-moving and highly informative but somewhat sobering discussion.
Naim Alkhouri and Dr. Rashmee Patil of the South Texas Research Institute join the Surfers to discuss practical challenges and issues in conducting on-time, on-target NASH clinical trials.
The January 29 FDA webcast on NASH Drug Development suggested the need for larger, longer clinical trials with more patients in the overall dataset. This week, Stephen Harrison, Naim Alkhouri, and Rashmee Patil of the South Texas Research Institute (each of whom manages hepatology clinical trial sites) discuss how to make trials run better and more smoothly. The trick is to be realistic about what is feasible and not to let "right" become the enemy of "good." The three researchers discuss specific protocol criteria that hamper success and share illustrative stories from their past. If you design clinical trials, need the results of trials to move your project or product forward, or assess trials for investment purposes, this episode will give you a clearer sense of when and how it makes sense to be more flexible in your design criteria and expectations. In the end, Louise and Roger each commented on how much they had learned.
NEW CONTENT: Suneil Hosmane joins Roger Green to discuss why he found the FDA Webcast so encouraging for liquid biomarkers.
BONUS INTERVIEW: GenFit Global Head of Diagnostics Suneil Hosmane joined Roger Green for a post-FDA Webcast interview. Suneil expressed general optimism about the Webcast. Like the Surfers, he appreciated the agency's request for data to begin answering pivotal questions about diagnostics and proof of benefit. Unlike the Surfers, he extended the conversation toward what he sees as an extremely promising path for current and future biomarkers to drive faster and more prognostic patient assessment, targeting, and care. He presents a very exciting view of how patient treatment might improve over the next few years even without new medicines. A short but stimulating conversation.
NEW CONTENT: Prof. Dr. Jörn M. Schattenberg joins Roger Green to discuss his highly optimistic reaction to the FDA Webcast.
BONUS INTERVIEW: Prof. Dr. Jörn M. Schattenberg and Roger Green spend 20 minutes discussing Jörn's reaction to the January 29 FDA Webcast. Joern discusses why digital pathology is such a benefit to trial sites outside the US and some of the new clinical development and sample size considerations emanating from a need to provide more robust safety data. An interesting, informative conversation.
The Surfers and guests Manal Abdelmalek, Naim Alkhouri, and Akero Therapeutics Chief Development Officer Kitty Yale discuss sections of the FDA Webcast that centered on drug development and clinical trial strategies.
The panel discussed key takeaways from the FDA webcast on NASH Drug Development on the subjects of clinical trial design and development strategies. Much discussion centered around parallel clinical trials for F2/F3 and controlled cirrhotic patients, both in terms of rethinking endpoints (is it sufficient to "halt" progression?) and designing sets of parallel trials to the sponsor's best benefit. Another key topic involved combination of combination therapies and practical issues around moving to combination approvals prior to having an acceptable set of monotherapies available. The third major area of interest involved length of trial for newer medications that are producing dramatic Phase 2 results in as little as 12-16 weeks.
The Surfers and guests Manal Abdelmalek, Naim Alkhouri and Akero Therapeutics Chief Development Officer Kitty Yale discuss sections of the FDA Webcast that centered on clinical and surrogate endpoints.
The panel discussed key takeaways from the FDA webcast on NASH Drug Development on the subject of endpoints. The group focused discussion on a few issues: (a) histology, both in terms of its continued primacy as a surrogate for pre-cirrhotics and FDA's willingness to accept digital histology; (b) ratification that "the goalposts" are not moving on the endpoint issue; (c) frank statement that risk: benefit ratio will shape how the agency evaluates drug candidates, and (d) histopath adjudication.
The Surfers and guests Manal Abdelmalek, Naim Alkhouri and Akero Therapeutics Chief Development Officer Kitty Yale share high-level perspectives on the FDA Webcast, both before and after the group's detailed conversation.
The panel shared overall impressions and key takeaways from the FDA webcast on NASH Drug Development, both before and after the detailed discussion. Key issues included the agency's continued reliance on histology coupled with a willingness to accept digital pathology results, the importance of risk: benefit ratio in drug evaluation, the importance of a composite fibrosis+steatosis endpoint, and new approaches to clinical trials for cirrhosis.
Manal Abdelmalek joins the Surfers to discuss key themes they hope to hear at the January 29 FDA Webcast on NASH Drug Development.
In this conversation, Professor Manal Abdelmalek joins the Surfers to explore some of the specific items for which they hope the FDA will provide clear guidance at its January 29 webcast on NASH Drug Development. Key issues included: (a) how to manage sample sizes with both safety issues and the need for patient heterogeneity in mind, and (b) whether we can seek to reduce screen fail rates by utilizing high-value non-invasive tests like MR elastography and MRI-PDFF in qualifying patients for clinical trials.
Manal Abdelmalek joins the Surfers to discuss key themes they hope to hear at the January 29 FDA Webcast on NASH Drug Development.
In this conversation, Professor Manal Abdelmalek joins the Surfers to explore some of the major themes they hope the FDA will address at its January 29 webcast on NASH Drug Development. Key issues included: implications of safety: efficacy tradeoffs in the approval process, expanding use of non-invasive testing during Phase 2 trials, and language in the agency's white paper suggesting that Phase 3 trials possibly should be two years or longer.
Manal Abdelmalek, Naim Alkhouri, and Akero Therapeutics Chief Development Officer Kitty Yale join the Surfers to discuss Friday's FDA webcast on NASH Drug Development.
Friday's FDA Webcast on NASH drug development provided few concrete answers but several clues and directions to pursue. Listen as Manal Abdelmalek, Naim Alkhouri, and Kitty Yale, Chief Development Officer at Akero Therapeutics, join the Surfers to read the tea leaves and identify fruitful areas for further research and pursuit. Issues around diagnostics and the risk: benefit tradeoff received particular attention.
Manal Abdelmalek joins the Surfers to share expectations in advance of Friday's FDA Webcast on NASH Drug Development.
FDA's Friday webcast titled "Regulatory Perspectives for Development of Drugs for Treatment of NASH" is the agency's long-awaited public event to provide better definition on what trial must achieve for a NASH drug to gain approval. In advance of that event, Stephen, Louise, Manal and Roger share expectations for that session. Kitty Yale, Chief Development Officer for Akero Therapeutics and a participant in our post-session podcast, sends in four points to explore. Whether you care about the process of drug development or simply the results in terms of drug approvals, you will find this episode a thought-provoking prequel to the actual event.
The Surfers discuss ways that COVID-19 Vaccine Centers might present an opportunity to educate and screen patients on Liver Health
Stephen Harrison suggests that COVID-19 Vaccine Centers might be an excellent site for providing screening and education around Liver Health and the conversation explodes with ideas and enthusiasm. In the span of 15 minutes, the group explores ideas for endorsers, volunteer educators and on-site testing, all based on the expectation that patients at a vaccine center (a) have downtime while waiting at the center and (b) show obvious interest in their own health. Listen for inspiration and ideas.
Donna Cryer and Louise Campbell discuss how governmental action (or inaction) couple with community efforts to shape Liver Health initiatives in the US, UK, and Australia.
The Surfers discuss challenges facing Disadvantaged Minorities in the US, UK and Australia related to Liver Health issues. Donna Cryer covers US issues, including structural challenges within the healthcare system and insufficiency of information, and also discusses community and culture-driven solutions. Louise Campbell contrasts issues facing populations in the UK and Australia, focusing heavily on diet-related health challenges facing Aboriginal and Indigenous people and Torres Strait Islanders in Australia
Donna Cryer joins the Surfers to explore efforts to support residents in disadvantaged minority communities in the US, UK, and Australia in improving their Liver Health and awareness."The Band gets together again" as Donna Cryer joins Stephen, Louise, and Roger to explore the state of Liver Health and Health Education in disadvantaged minority communities. In the first part of the episode, the group discusses how governmental action (or inaction) couple with community efforts to shape Liver Health initiatives in the US, UK, and Australia. In the second part, the group discusses ways to galvanize education and testing activities around the Vaccine Centers that have sprung up in all three countries. If you want to help disadvantaged populations, and particularly racial or ethnic minorities, improve their own prognosis by improving Liver Health, THIS IS YOUR CALL TO ACTION!
The Surfers end this episode by discussing the need for public education to create the awareness necessary for change.
This conversation covers a broad range of topics -- public health needs in different parts of the world, non-communicable disease, public awareness -- but ends in a discussion on the need for public and industry sponsorship to support the broad scale of education needed to create the level of public awareness necessary to change behavior.
Evaluating the economic and patient-motivating value of enhanced telemedicine and mobile non-invasive testing technologies in improving NAFLD diagnosis and lowering rates of non-communicable disease.
The Surfers and our guest Dr. Manal Abdelmalek consider the economic costs and value of enhanced telemedicine and mobile “de-liver” testing technology and then move on to consider critical success factors in making these innovations patient-friendly and motivating patients to take advantage of them.
Innovations in Telemedicine and Mobile Technologies are already changing patient care in ways that will remain and expand in the "New Normal" after the COVID-19 pandemic is less urgent.
Our guest, Dr. Manal Abdelmalek discusses how a rough week in patient-management led her to envision innovative ways to incorporate telemedicine and mobile technologies such as FibroScan and non-invasive blood tests like NIS-4, ELF, and FIB-4, into patient care. Stephen Harrison and Louise Campbell build on Manal’s concept.
Manal Abdelmalek joins the Surfers to describe long-term changes in patient management that improved diagnostic and telecommunication technologies can drive in response to new COVID-19 induced challenges.
How must we adapt to the changes in patient management caused by COVID-19? The Surfers, spurred by creative ideas from guest Manal Abdelmalek, think about ways to re-engineer patient communication and treatment, including innovations in patient-management and out-of-office diagnostics. Whether discussing "de-livery" vans loaded with complete sets of diagnostic tools or the use of colors, icons, and one-letter code to convey the results of lab tests, the Surfers surface an array of creative concepts for our future.
Question: If NALFD patients have poorer COVID-19 prognoses, how can we use this fact to drive broader population-based screening?
This conversation asks a two-part question: How do we motivate primary care treaters and specialists who treat metabolic syndromes to manage NAFLD more aggressively? The conversation considers education and telemedicine in this context and then turns to two very ambitious concepts. One of these deals with screening, the other with treatment before approvals. Listen until the end then let us know what you think and what big ideas you, yourself might have.
The COVID-19 conversation continues with the group focusing on challenges in clinical trial execution and how innovative logistics and consistent education can lessen or overcome them.
In this conversation, the group starts by discussing the significant number of patients who could benefit from NAFLD or NASH therapy centered around defatting the liver through medications and behavioral support and proceeds to address ways to manage these issues in a pandemic for a disease with no approved medications. Louise discusses the importance of broad monitoring for patients who might have an early-stage disease, Stephen comments on the importance of education and Manal provides examples of successful "out-of-the-box" patient management programs such as simple home-based "Lab and Leave" visits. The conversation is filled with real passion and enthusiasm for solving new challenges.
Manal Abdelmalek joins the Surfers to consider the three most important COVID-19 stories today.
The conversation focuses on the British variant, the new vaccines, and the physical and emotional toll the pandemic continues to take on front-line physicians and other healthcare workers. Stephen and Manal each have a sibling who works as an ER physician and they provide heart-wrenching stories on how tough the front lines are. Louise discusses how Britain is reacting to government policy designed to contain the new, more contagious COVID-19 variant. Roger discusses possible epidemiological trends and explains why the US may eventually follow the UK policy of delivering the first doses of the vaccine as quickly as possible. Thought-provoking in its own right, the discussion helps frame treatment and policy choices as well as the rest of this episode.
Manal Abdelmalek joins the Surfers to discuss how recent COVID-19 news might affect Fatty Liver patients and what the medical profession and BioPharma companies can do to support patients better during this dangerous phase of the pandemic.
Manal Abdelmalek joins the Surfers to discuss the implications of the new British COVID-19 variant, availability of the Pfizer/BioNTech and Moderna vaccines and impact of social distancing on patients with Fatty Liver Disease. The discussion starts by surveying the current situation and goes on to discuss challenges for patients and provider and then keys to maximum success in conducting clinical trials and treating patients. In the end, Stephen Harrison and Roger Green propose big, bold solutions to improve diagnosis and patient care.
Wayne Eskridge describes how hope fell and then rose as patients did not receive the drug approval they expected but then learned about exciting paths for new agents and non-invasive testing.
Wayne Eskridge describes his excitement as 2020 ends, saying "The quality of the work that's being done overall says that this is a far more tractable problem than we thought it was a couple of years ago. The level of sophistication that's being applied was undreamed of by the profession five years ago. So I'm very, very confident that we're going to see effective therapies," before cautioning, "How many jumps we have to get past to get there, I don't know." His excitement centers around very positive Phase 2 trials for multiple drugs with innovative modes of action and major advances in research and acceptance of non-invasive tests.
Louise Campbell questions the implication of APASL and ALEH endorsing "MAFLD" as Fatty Liver Disease nomenclature and Stephen Harrison discusses behind-the-scenes activities to resolve this issue.
Louise Campbell "wonders" where increased support for adopting the term "MAFLD" (Metabolic-Associated Fatty Liver Disease) instead of NAFLD (Non-Alcoholic Fatty Liver Disease) "is going to take us in the next 12 months and how we are going to come to a resolution." In response Stephen Harrison provides background on how the dispute started and discusses the current multi-regional efforts to create consensus around a nomenclature that describes the range of Fatty Liver Diseases accurately.
Joern Schattenberg discusses the public health implications of German newspapers beginning to discuss Fatty Liver Disease
For Joern Schattenberg, reading about Non-Alcoholic Fatty Liver Disease in a German newspaper "has two or three very important implications that we have discussed on the podcast in the past year," particularly in terms of educating patients with metabolic syndromes and families with obese children or adolescents. Increasing awareness of late-stage liver fibrosis and cirrhosis will bring short-term benefits to one set of patients, while reducing the frequency of liver disease in the young will have long-term benefits for these patients and the society at large.
Ian Rowe discusses how streamlined use of ELF, FIB-4 and FibroScan improves cost effectiveness and patient satisfaction associated with NASH screening.
Ian Rowe comments on data from the landmark work he, Richard Parker and colleagues in Leeds, UK are conducting around the issue of population screening for NASH: "it's quite easy to show that you can identify more liver disease in the community and you can do so more efficiently." This short interview goes into detail.
Guests Ian Rowe, Joern Schattenberg and Wayne Eskridge join the Surfers to discuss key lessons learned in 2020 about Patient Treatment and Perspectives.
Ian Rowe, Joern Schattenberg and Wayne Eskridge join the Surfers to explore some of the key lessons learned and issues uncovered in 2020. Ian Rowe discusses what population-level research in Leeds, UK, tells us about the benefits a streamlined liver testing model can yield not only in terms of better, faster diagnoses but also cost savings and improvement in patient satisfaction. Joern Schattenberg considers the implications when German mass media raises issues of Fatty Liver Disease in holiday season news stories. Louise Campbell questions what a patient-supported push to change the disease nomenclature from NAFLD to MAFLD implies for the future, while Stephen Harrison describes the emerging effort to get the most accurate and clearest nomenclature possible. Finally, Wayne Eskridge provides his perspective as patient and patient advocate on a year full of both happy surprises and disappointments and he finds himself surprised to be more optimistic at the end of 2020 than at the beginning.
Roger Green discusses why despite widespread concerns, FDA's Complete Response Letter to Intercept did not cripple progress in NASH drug development.
Observers feared that after Intercept received its CRL, investment into NASH drug development would dry up and knowledge would slow. Instead, Roger Green describes how drugs that had reached Phase 2 development maintained sufficient momentum to move forward. As a result, therapeutic focus shifted from treating fibrosis in late stage patients (obeticholic acid's benefit) to treating the whole patient, including not only NASH but the full range of metabolic considerations. Net result: the vibrant, "boiling hot" market for NASH clnical trials and researchers that Vlad Ratziu described and the prospects that several exciting classes of NASH drugs will be here soon.
Stephen Harrison summarizes a year of progress in improving the tests and analyses used to derive clinical endpoints necessary to initial drug approvals.
Despite reports earlier in the year, Stephen Harrison discusses the "aggressive, conscientious effort" an array of stakeholders is making to improve on the clinical endpoints that shape the decision to approve a Fatty Liver Disease drug before it has demonstrated positive outcomes for patients and the healthcare system. Three keys: (1) more rigorous human review of biopsy slides, (2) an eventual shift to incorporate Artificial Intelligence and, someday, (3) use of AI and non-invasive tests as a complete plan for developing these clinincal endpoints.
Mazen Noureddin describes a year in which biopsy's shortcomings are revealed at the same time as non-invasive testing becomes better and produces more robust data.
Mazen Noureddin discusses the simultaneous loss of faith in biopsy as the clinical "Gold Standard" and the emergence of non-invasive tests that can become the standard and replace biopsy for three pivotal diagnostic needs:
- Identifying patients at risk, those with fibrosis levels equal to or higher than F2
- Identifying patients who can serve as targets for clinical trial, which usually means they have NASH levels or at least N4 along with fibrosis greater than or equal to F2
- Monitoring therapeutic responsiveness in both sets of patients over time without the need for serial biopsy.
Vlad Ratziu discusses a "boiling hot" field of emerging NASH drugs and "particularly rich" data coming from no-invasive diagnostic testing.
Despite elafibranor failing, obeticholic acid not securing FDA approval and COVID-19 related limitations in the conduct of clinical trials, "this was a very good year actually for NASH clinical trials," with "some significant advances in terms of therapeutics for NASH" and . We had the results of several trials this year. We had the unfolding story of other molecules that are in development for NASH and all this makes for a very, very vibrant environment in terms of therapeutic research for NASH." Further, MRI-based methods "are becoming mainstream," starting to fulfill the promise of non-invasive testing.
The Surfers and guests Vlad Ratziu and Mazen Noureddin discuss key lessons learned in 2020 about Drugs and Diagnostics.
Vlad Ratziu and Mazen Noureddin join the Surfers to explore some of the key lessons learned and issues uncovered in 2020. Vlad Ratziu provides a 10-minute overview of a fast-paced year of successes (and occasional failures) in clinical trials and novel diagnostics. Mazen Noureddin discusses the expanding role of non-invasive liver tests in diagnosis, patient treatment and monitoring and drug development. Stephen Harrison updates our knowledge about the use of clinical endpoints in obtaining conditional drug approvals. Finally, Roger Green places the entire year in a systems context with an eye toward the Law of Unintended Consequences and why the obeticholic acid Complete Response Letter was not the death knell many observers feared.
Donna Cryer and Global Liver Institute Director of Policy Andrew Scott return to discuss their 2021 US NASH Action Plan, garnering support for the new COVID-19 vaccines and the importance of aligning stakeholders with Stephen, Louise and Roger.
The Surfers end the year on an optimistic note by talking with sometime-surfer Donna Cryer and GLI Director of Policy Andrew Scott about GLI's ambitious 2021 US NASH Action Plan, which should be released by the time you read this. The plan seeks to align all groups of key NASH stakeholders around common goals to provide appropriate diagnostics, therapy and support for NAFLD and NASH. The panel also considers time discussing acceptance and rate of uptake for the COVID-19 vaccines and the nature of leadership in a complex situation like the one NASH faces throughout the world. An episode full of new information, different viewpoints and positive energy to end what has been a truly challenging year.
Donna Cryer and Global Liver Institute Director of Policy Andrew Scott join Stephen, Louise and Roger to discuss the policy progress liver disease and NASH have made in the last four years.
This is the first of two epiodes discussing Public Policy questions that affect how stakeholders view NAFLD andNASH as a disease as well as the process by which related drugs and diagnostics are evaluated. Today's episode addresses the many kinds of progress that liver policy has made in the past four years, ranging from a bipartisan NASH Act awaiting action in Congress to increasing alignment with other medical specialties and disease advocates to work together on NASH as part of a multi-system metabolic health platform. The theme was "convergence" -- people and organizations coming together to consider the liver more broadly in the context of overall health.
Dr Ian Rowe and Prof. Dr. Jörn M. Schattenberg joins the Surfers to explore the relationship between NAFLD and CVD in light of recent work questioning the strength of links between the two
This episode asks how to reconcile results from a presentation at EASL suggesting that the primary cause of death from NAFLD patients is liver disease and the low level of CVD events in the STELLAR-3 and STELLAR-4 trials with significant other data identifying CVD as the leading cause of death in NAFLD patients. The group determined that design issues led to the low level of CVD events in the various study populations, then confirmed the importance of the link. Finally, we explored implications in terms of patient care and clinical trial design.
Guest Ian Rowe and Dr. Kris Kowdley join the Surfers to discuss how the 2nd COVID wave and arrival of the vaccine are likely to affect patient treatment and clinical development.
In Episode 39, hepatologists Ian Rowe and Kris Kowdley, who divide their time more or less evenly between patient clinics and clinical trials, join the Surfers to discuss how the Second Wave of COVID-19 will affect patient treatment and clinical trials. This conversation turns conventional wisdom on its ear. The Surfers focused less on individuals' behavior and more on supply chain disruptions, growing shortfalls in the number of available healthcare workers and large-scale dislocations that will occur after the vaccine is in place. This episode challenges underlying assumptions about how the next few years might evolve and what will matter most.
Prof. Vlad Ratziu, MD, and Prof. Dr. Jörn M. Schattenberg join the Surfers to wrap up our conversation about this year's AASLD meeting.
Prof. Dr. Jörn M. Schattenberg erg and Prof. Vlad Ratziu, MD join the Surfers for our wrap-up episode for TLMdX 2020. Joern focuses on a diabetes poster demonstrating the path of drug efficacy over a three-year period, while Vlad focuses on the successful Phase 2 trial of the pan-PPAR lanifibranor. The group also asks why placebo response varies so much between studies and whether the ratio of F2:F3 patients may be a factor. Finally, the Surfers focuses on what they consider the biggest lessons emerging from the meeting.
The Surfers spend the final day of AASLD 2020 looking at two very different sets of issues. Issue 1: challenges proving efficacy in F2 populations, particularly in terms of fibrosis. Issue 2: social burdens of poor dietary choices around the world, particularly given how developing PNAFLD (pediatric non-alcoholic fatty liver disease) can create a metabolic burden that can last a lifetime. In the end, the group remained optimistic about the explosion of knowledge around drugs and diagnostics for NASH and NAFLD but troubled by the lack of social policy, awareness or education around these issues.
Reviews of Phase 2 drug trials and diagnostic strategies reveal that NASH is close to multiple breakthroughs.
Naim Alkhouri and Mazen Noureddin join Louise and Roger to review highlights from Sunday at The Digital Liver Meeting. Naim, Mazen and Roger review results from drug trials that reveal that multiple drugs (monotherapies and combinations) with potent effects on liver fat reduction and fibrosis are moving through the pipeline. Louise discusses a trial that relies on non-invasive techniques to assess histologic improvement and fibrosis regression in cirrhotic patients, signaling one more way that non-invasive techniques might replace biopsy. Finally, Louise and Roger team up to discuss a US-based 20-year study showing us the many ways that lean NASH prognosis and co-morbidities differ from overweight or obese NASH. A session filled with information, theorizing and high spirits!
Manal Abdelmalek joins the Surfers to review some of Saturday's most exciting presentations and posters from AASLD 2020, followed by a discussion of an exciting new hand-held diagnostic.
Manal Abdelmalek joins the Surfers in a free-flowing discussion of Saturday's key papers and posters. Much of the talk focused on Lean NASH -- what it is some of the new diagnostic analyses and algorithms used to identify patients with or at risk of the disease. Stephen talked about the extraordinary path that seladelpar took through its Phase 2 NASH trial and Roger revisited an old podcast question: can Patient-Reported Outcomes be part of clinical development planning and, if so, for what kinds of drugs. Finally, the Surfers welcomed Dr. Nezam Afdhal of Harvard and George Aliphteras of Sonic Incytes in a sponsored extra-sode that is part of the rollout of Velacur, their handheld liver health assessment device. The discussion moved quickly and at the end, all the Surfers were struck powerfully by how dynamically we are learning about this disease.
Prof. Dr. Jörn M. Schattenberg joins the Surfers to discuss his recent article in Expert Opinion on Investigational Drugs dissecting recent drug trial failures.
Prof. Dr. Jörn M. Schattenberg joins Stephen, Donna, Louise and Roger to discuss his recent article "The Nonalcoholic Steatohepatitis (NASH) drug development graveyard: established hurdles and planning for future successes." The discussion started with lessons from failed trials, focusing on the importance of utilizing Phase 2 trials to test hypotheses and establish appropriate targets. From there, Surfers went on to discuss commercial and patient-focused definitions of what makes a clinical trial successful.
Stephen Harrison, Roger Green and our guest Surfer, Dr. Manal Abdelmalek, identify pivotally important presentations and posters from The Digital Liver Meeting 2020
SurfingNASH continues our AASLD coverage by asking Stephen Harrison, Roger Green, and guest Surfer Dr. Manal Abdelmalek to identify and review abstracts they consider important or uniquely interesting. The abstracts they chose focus on exciting new agents, the emerging role of #artificialintelligence (AI) and machine learning inpatient diagnostics, and several issues surrounding lean NASH. AI-guided patient-level diagnostics? The story that emerges: a world where patients are diagnosed earlier and treated with agents that drive rapid response. Better liver health, better treatment of the entire range of metabolic non-communicable diseases...very intriguing!
Louise Campbell, Donna Cryer, and Naim Alkhouri identify pivotally important presentations and posters from The Digital Liver Meeting 2020.
SurfingNASH kicks off its AASLD coverage by announcing four of our seven KOL guest Surfers. One of them, Dr. Naim Alkhouri, participates via interview. Naim, Louise Campbell, and Donna Cryer identify abstracts they consider important or uniquely interesting. The abstracts they chose focus on population health (particularly juvenile and pediatric NASH) and the link between NASH, obesity, metabolic factors, and death due to cancer. The issue of treating pediatric and adolescent NASH is tremendously challenging with issues involving diagnosis (are biopsies in children a good idea?), new agent testing (is the benefit ration for clinical trials in adolescents and pediatrics worth the risk?), and social education (how and what do we teach families)? An important and thoughtful episode for healthcare providers as well as anyone interested in public health or forecasting future use of medications and diagnostics.
Guest Surfer and regular listener Dr. Ian Rowe joins the Surfers to discuss how everyday patient treatment in the clinic once was and how COVID-19 and the news we discuss weekly on SurfingNASH have changed practice.
This week's Guest Surfer, Dr. Ian Rowe, devotes roughly half his time to treating patients in his Hepatology practice in Leeds, UK, and the other half on research and teaching issues. He joined the Surfers to discuss how patients were referred to his clinic and how he treated them before COVID-19, and how the demands of the pandemic have changed practices in the clinic. Not surprisingly, the conversation turned to the best way to use the diagnostics we have and how events of the past year have increased the productive focus on using better diagnostics while simultaneously using diagnostics better. Along the way, learn about a significant research effort (350,000 patient records!) Dr. Rowe and his colleague, Dr. Richard Parker have undertaken and why sequential use of multiple non-invasive tests may offer the winning strategy for improving patient treatment.
On the six-month anniversary of SurfingNASH's first episode, the Surfers stop to consider how much has changed for NASH stakeholders since April
Thursday marks the six-month anniversary of SurfingNASH's first episode. The last six months have seen both setbacks and large steps forward in drug development, major advances in disease knowledge and increased breadth and depth of patient advocacy. The Surfers reflect on all these changes while remembering key steps in the podcast's evolution. Past guest Surfers Tony Villiotti of NASH kNOWledge and Suneil Hosmane of GenFit add their own reflections about what has changed.
Matt Kelly, Chief Innovation Officer at Perspectum, Ltd., joins the Surfers to discuss early findings from the COVERSCAN study which looks at the relationship between COVID-19 infection and major end-organ systems.
Matt Kelly, Chief Innovation Officer at Perspectum, Ltd. joins the Surfers to discuss two studies that look at the relationship between COVID-19 and the liver. In the COVERSCAN study, Perspectum plans to conduct multi-organ scans of 500 patients who have recovered from a COVID-19 infection at two-time points: post-infection and six months later. The goal was to establish the impact of the COVID-19 infection on all the body's major organ systems. During this podcast, Matt discusses the results of the first round of scans on the first 200 patients. In the current UK BioBank analysis, UK BioBank culled through its database of 500,000 patients aged 40-75 to find 1,000 who had prior COVID-19 tests and imaging and compared the 10% of these patients who tested positive to the rest of the cohort. Both sets of results suggest a complicated relationship between fatty liver and severity of COVID-19 infection. This new research is producing eye-opening results that challenge conventional thinking. Perhaps our most important episode to date...
Browse Our NASH and COVID-19 Coveragehttps://surfingnash.com/covid-19/
Stephen Harrison leads the Surfers through a review of FGF-21s and other exciting drug development news.
Stephen Harrison starts this week's discussion reviewing the recent announcement of a promising Phase 1b/2a study for 89bio-100 (link to slide deck below), an FGF-21 agent that demonstrated significant reductions on liver fat and had positive effects on other metabolic measures. The discussion broadened to address an array of issues: other agents in development; changing (higher) expectations for how these agents will affect PDFF and possibly fibrosis; possible directions for combination therapy; and the five clinical values that collectively tell us the impact new medications can have on overall liver and metabolic health. One Surfer described this as a "brilliant 20-minute review."
89bio-slide deck: http://bit.ly/89bio-report
The Surfers discuss four issues that are likely to affect how our thinking about NASH diagnosis, education, and treatment might evolve over the next three months.
Naim Alkhouri joins the Surfers to discuss some key NASH-related questions. The four key sections address upcoming clinical trials, steps forward in patient advocacy, the UK NCD report and need for patient education, and the pervasive impact of COVID-19 on how we think and talk about liver disease. Always lively, always provocative, and occasionally humorous, this episode is worth a long listen.
Browse Our NASH and COVID-19 Coveragehttps://surfingnash.com/covid-19/
The Surfers discuss the Global Liver Institute's campaign to educate and motivate key stakeholder groups on the value of non-invasive liver testing.
Donna Cryer, President and CEO of the Global Liver Institute, discusses GLI's "Beyond the Biopsy" campaign while Stephen Harrison, Louise Campbell, and Roger Green join in with education, messages, and ideas. The "Beyond the Biopsy" campaign focuses on the importance of gaining acceptance for non-invasive liver testing. Stephen discusses why validation matters and why "H" is a magic letter. Roger discusses the history of statins and the importance of what appears on blood testing results. Louise discusses simple things that healthcare can do to diagnose and treat liver disease before it becomes deadly. An eye-opening episode!
The Surfers and guest Joern Schattenberg consider the implications of a Digital ILC presentation stating that the liver, not cardiovascular disease, is the leading cause of death for NAFLD patients.
The Surfers considered the implication of a Digital ILC presentation by James Paik et al. titled "Causes of death in patients with non-alcoholic fatty liver disease (NAFLD): data from national vital statistics system (NVSS)." The presentation demonstrated that liver disease, not cardiovascular, is the leading cause of death for NAFLD patients, with broad implications for treating early-stage patients. Surfers asked: If NAFLD patients "feel bad" all the time, can patient-reported outcomes become a primary measure? Shouldn't metabolic measures remain vitally important for patients most of whom are obese and exhibit concomitant Type 2 diabetes or cardiovascular disease? And which test(s) provide the greatest support for FibroScan in demonstrating positive predictive value? A tremendous amount of content and tips from Dr. Harrison and Prof. Schattenberg. You'll want to listen more than once!
Professors Joern Shcattenberg and Vlad Ratziu join the Surfers to discuss the lessons and findings we can take away from Digital ILC 2020.
What happens when seven people with diverse and divergent perspectives consider the implications of last week's Digital ILC meeting? Professors Vlad Ratziu and Joern Schattenberg join the Surfers to reflect on many insights, some leading to clashing outlooks. From Peter Traber's opening comments about the increasing convergence and energy around NASH to a closing discussion on how a finding on that liver disease is, in fact, the leading cause of mortality in NAFLD patients (a finding that, in the words of one Surfer, "stood things on their head," ) this was a rollicking, passionate conversation with equal parts agreement, challenge, mutual respect and, of course, humor. Listen twice to get all the small points!
SurfingNASH's Digital ILC coverage ends with three late-breaking drug presentations, a discussion of EASL's COVID efforts, and insights on patient management.
Professor Joern Schattenberg joins the Surfers to discuss the last day of Digital ILC. Donna Cryer and Roger Green praise the work EASL has done pulling together data and analysis on how #liverdisease affects #COVID19 treatment decisions and outcomes, while Louise Campbell discusses research-in-process and Stephen, Peter Traber and Prof. Dr. Jörn M. Schattenberg discuss two exciting drugs in development and combination therapy that teaches us lessons about underlying liver dysfunction. In the end, Donna discusses GLI's "Beyond the Biopsy" initiative. This episode is knowledge-dense but entertaining... and totally a "can't miss" episode!
Browse Our NASH and COVID-19 Coveragehttps://surfingnash.com/covid-19/
Drugs in development and diagnostics show promise but healthcare has far to go in identifying and treating patients in need.
Professor Vlad Ratziu joins the Surfers to discuss Day Two's presentation. The day produced exciting presentations about drugs in development and suggestive findings of the role non-invasive tests and markers can play in predicting patient success. At the same time, other presentations focused on the challenges and opportunities involved in identifying and treating patients earlier in the course of the disease. The group explored issues in detail, leading to a longer conversation that was both thoughtful and rollicking. SPOILER ALERT: Four of the six Surfers made some form of reference to the Bible...
Today's podcast is sponsored by Sonic Incytes Medical Corp., manufacturer of Velacur™. Velacur™ is the first handheld 3D liver health assessment tool that is fast, accurate, intelligent, and portable. A 25-minute discussion with George Aliphteras, CEO of Sonic Incytes and Dr. Michael Curry, lead author of poster FRI-050, which discusses Velacur, starts at 1:22:11 and runs ~26 minutes.
One day into the first-ever digital major conference, the Surfers review six presentations and one interactive session. A lot was learned, much of which did not fit into neat categories.
The Surfers and guest Naim Alkhouri reviewed six presentations and one interactive session formally (points from other presentations crept in once or twice). Like the day itself, the group came to a few clear conclusions or consensus, except that AI/machine learning has a larger role to play going forward and that liver biopsy will play a pivotal role in the foreseeable future. This session runs well over an hour but is packed with information, insights, and questions.
The group discusses the plusses and minuses of digital conferences compared to traditional in-person events.
Digital ILC starts Thursday, August 27. Donna Cryer, who oversaw the first Digital International NASH Day this year, and Stephen Harrison, who co-chairs NASH-TAG, discuss the factors that organizers consider when deciding whether to go digital and planning how to make it work. The discussion reveals some powerful benefits for a digital meeting in terms of how many people and which new groups can attend, as well as drawbacks in terms of spontaneity and events that build personal bridges and unusual ideas. You will never look at any kind of major meeting the same way after you listen to this.
The second part of the "What NASH patients want" series focuses on the future of healthcare apps and the role government agencies such as FDA, NIH, CMS, and EMEA can play in providing hope or increasing concern and anxiety based on their decisions and the consistency of their messages. In discussing apps, Fatty Liver Foundation President Wayne Eskridge, a trained electrical engineer, envisions a future when patients can receive continuous readings on key metrics using an implanted device that derives its power by burning the patient's glucose or fat, while the other Surfers lend their own thoughts and perspectives. In discussing the government, GLI President & CEO Donna Cryer and Wayne Eskridge discuss the need for the government to take an integrated approach to liver health. Specific points of action include two proposed pieces of legislation( the Liver Illness Visibility Act ad the Treat and Reduce Obesity Act) and the idea that all the relevant institutes within NIH would work on an integrated plan for liver disease. Finally, the Surfers discuss the need for the FDA to act from a place of transparency and patient engagement, particularly around the risk: benefit ratio for new medicines. Again, the other Surfers ask questions and share ideas. The music from Jeff Ramsdale provides a fantastic exit note.
Patient advocates discuss how doctors and other providers can serve patient needs better
Guest surfer Anthony Villiotti, President of NASH kNOWledge, Inc. joins the Surfers. Tony and Surfer Donna Cryer, President & CEO of Global Liver Institute, discuss the way that better delivery of disease information and care can keep patients healthier longer and make them more knowledgeable about their disease. Too often patients are told not to worry about a fatty liver until the day they learn they need a transplant -- this has to stop! Learn how we developed our word of the week ("indoctrinologist"), why the "What? So what? Now what?" approach would be valuable, and how timely information and coordinated care will lead to better patient outcomes.
Donna Cryer, President & CEO of the Global Liver Institute, and Louise Campbell, Founder of Tawazun Health, become Surfing regulars in an episode focused on the pivotal papers at EASL's Digital ILC meeting August 27-29. The group discusses the section addressing COVID-19 and liver disease links along with presentations and posters discussing use of FibroScan, AI-aided test analysis, reducing cardiovascular risk by treating NAFLD and evaluating liver fibrosis in diabetes workups. The group also discussed cultural issues in NASH patient education and answer a letter about supporting Fatty Liver treatment in Africa. A truly multi-disciplinary look at this important meeting. THIS WEEK'S MUSIC: Mr. Parr is a musician and a 6th-grade teacher in Franklin Lakes, NJ, who produces music to teach students different elements of science. He is a two-time teacher of the year winner whose songs have been played on the Weather Channel, YouTube and Science Curriculum networks. You can find his songs through teacherspayteachers.com.
The Surfers focus on steps Allied Health Professions and passionate physicians can take to improve lifestyle compliance with #NASH and #NAFLD therapies. The group explores whether the healthcare system can be as effective as companies like Noom and WeightWatchers. This week's Music from the Liver Community: beautiful Oud music from Dr. Naim Alkhouri.
FOCUS: Some of the presentations that will make NASH/NAFLD news next month
Transplant hepatologist Naim Alkhouri joins the Surfers in discussing a dozen intriguing paper or session titles listed as part of the scientific program at next month’s Digital International Liver Congress. The discussion touches briefly on SurfingNASH’s plans for expanded Digital ILC coverage and even features a two-minute blues song from pharmaceutical economist and chart-busting blues artist Michissippi Mick Kolassa.
NASH is not merely a byproduct of obesity.The role the liver plays in non-liver comorbidities is complex and important. Join the Surfers as they give the liver the respect it’s due. “The ways liver affects outcomes is a very, very complex topic which, for the sake of argument, is sometimes simplified down to obesity…but like our perspective on NASH demonstrates, there's a lot going on.” – Suneil Hosmane
Browse Our NASH and COVID-19 Coveragehttps://surfingnash.com/covid-19/
FOCUS: Three sets of tools that will improve NASH disease understanding.
The Surfers return to diagnostics once more. This time, they explore the utility of novel blood and serum tests, assess the benefits of smaller imaging devices and consider the impact that artificial intelligence and machine learning can have in improving how we diagnose and what we learn from biopsies…one more piece of an exciting future for Fatty Liver stakeholders. #NASH #NAFLD #FattyLiverDisease
Decoding the message of Intercept’s Complete Response Letter
Former FDA Director Brian Harvey joins the Surfers to discuss what obeticholic acid’s rejection might mean for other NASH medicines in development. Is this the end of accelerated approvals? Does it simply mean we need better drugs? Join the debate
CONSENSUS: the big story will be the regrowth of COVID-19 in the US and its implications.
The Surfers discuss different elements of the evolving COVID-19 story — what it feels like to live in an emerging “hotspot” city, new findings on the impact Fatty Liver Disease may have on disease severity, and the commercial implications of all this. #NASH #NAFLD #FattyLiverDisease # COVID #COVID19
Browse Our NASH and COVID-19 Coveragehttps://surfingnash.com/covid-19/
What would create greater value for patients and providers?
Professor Mary Rinella of Northwestern University and Suneil Hosmane of GenFit join Stephen, Louise, and Roger to explore which of these strategies can do the most to improve patient diagnosis and management. The answer might surprise you.
Surfing the NASH Tsunami celebrates a growing and increasingly important global event for the Fatty Liver community.
Global Liver Institute President & CEO Donna Cryer joins the Surfers to discuss the focus, passion and advocacy that have shaped and grown International NASH Day. Learn how IND started and what it represents today. As you listen, envision the role you can play in the future of Fatty Liver advocacy and education.
Room for improvementGenFit Head of Global Diagnostics Suneil Hosmane joins the Surfers in exploring the current strengths and drawbacks of Fatty Liver diagnostics. The conversation considers the needs of drug developers, clinicians and patients, and highlights opportunities for improving diagnostic options.
Reviewing press releases reporting preliminary findings from six recently announced Phase 2 trials
Stephen Harrison leads the Surfers, with guest Louise Campbell, through an examination of six Phase 2 clinical trials that put forth press releases during the last three months. In all, the discussion created an air of optimism based on better clinical outcomes than we have seen with earlier NASH drugs, all from medicines with distinct but potentially complementary modes of action.
Exploring the controversy over the name(s) to use when describing Fatty Liver disease(s)
Professor Quentin Anstee joins the Surfers for a thoughtful consideration of the factors that should drive the decision on what name(s) to use for different Fatty Liver diseases. The group considers a range of issues from our level of scientific knowledge to the semiotics of naming to how patients react to certain disease descriptions, all in a stimulating, freewheeling discussion.
Clinical trial results that are changing how we look at NASH
Stephen Harrison leads a review of two recent Phase 3 data statements: the outcome of GenFit’s RESOLVE-IT trial and Madrigal Pharmaceuticals’ recent press release on the extension of its MAESTRO Phase 3 NASH trial. Listen to a thoughtful, far-reaching sometimes funny conversation as the group explores WILD TIMES IN NASH-VILLE – PART I.
Three possible scenarios for development of the NASH market.
Roger Green presents three possible directions for the NASH market over the next 5-10 years and asks our panelists, including our guest, renowned nurse and patient advocate Louise Campbell, to suggest critical market-driving factors.
Browse Our NASH and COVID-19 Coveragehttps://surfingnash.com/covid-19/
Critical considerations for companies developing NASH drugs
Peter Traber focuses on ways COVID-19 can affect drug development and broader corporate strategies while our panelists weigh in on implications for clinical researchers, investors and forecasters in our third episode: C-SUITE COVID-19 CHALLENGES.
Browse Our NASH and COVID-19 Coveragehttps://surfingnash.com/covid-19/
What investors want to know about NASH development during the pandemic.
Yasmeen Rahimi poses five questions NASH investors ask her about the impact of COVID-19 on NASH clinical and commercial development and our panelists provide answers in our second episode, FIVE $IMPLE PIECES: What investors want to know about NASH development during the pandemic.
Navigating NAFLD/NASH clinical trials through the pandemic
Dr. Stephen Harrison discusses several ways the pandemic is affecting planning and execution of clinical trials and our panelists discuss implications for investors, C-suite executives and forecasters in our first episode, COVID CHAOS: Navigating NAFLD/NASH clinical trials through the pandemic.
Browse Our NASH and COVID-19 Coveragehttps://surfingnash.com/covid-19/