Surfing the Nash Tsunami

Send us a textKey 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. 

Send us a textKey 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.

Send us a text00:00:00 - Surf's Up, Season 6, Episode 12This 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 ChangeNaim 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 states that 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. 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 providers come to view MASH similarly to how they view diabetic comorbidities. 

Send us a textThis 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.

Send us a textMulti-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. 

Send us a textMulti-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.

Send us a text00:00:00 - 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 introductionThe 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 useGuided 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 ClinicsLouise 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-upLouise 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 healthThis 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 - ConclusionBecause Roger is on vacation, there is no business report this week.

Send us a textThis 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.   

Send us a textRoger 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

Send us a textThis 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. 

Send us a text00:00 - Surf's Up 6.10.1This 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 patientsThe 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 - ConclusionThe business report discusses the next few episodes and asks who would like to meet Roger at Paris MASH.

Send us a textHepatologist 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.

Send us a textFatty 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.

Send us a textThis 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.

Send us a text00:00:00 - Surf's Up: Episode 6.9This 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 3Behavior 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 BetelThis 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 AlkhouriThis 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 - ConclusionThe business report discusses vacations on the SurfingMASH team, upcoming episodes, and grateful notes from Ukrainian listeners. 

Send us a textThis 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.

Send us a textGlobal 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.

Send us a textThis 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.

Send us a text00:00 - Surf's Up, Season 6 Episode 8The 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 2Behavior 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 HoldenGLI 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 4Sven 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 ReportThanks to our listeners, Jörn's vacation, Welcome Regeneron

Send us a textThis 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. 

Send us a textThis 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. 

Send us a textThis 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.

00:00:00 - Surf's Up: Season 6 Episode 7Host 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 SLDThis 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 ReportRoger highlights special September programming, indicates that new sponsors are on the way, and asks how many listeners find SurfingMASH on YouTube. 

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 2The 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 HinksonSummit 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 SummitNewly 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 - ConclusionAs part of this memorial week, Roger Green forgoes the usual business report, which will return next week.

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.

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. 

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. 

00:00:00 - Surf's Up: Season 6 Episode 5Host 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 OneThe 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 Jörh 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 ResmetiromNaga 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 ScienceScott 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 ReportAs Roger copes with his laryngitis, AI voices deliver an abbreviated business report 

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. 

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. 

his 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 Marie 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.

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 - IntroductionHost 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 4This 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 AdvocatesThis 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 EnvironmentHepatologist 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 Congress.

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. 

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. 

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. 

00:00:00 - Surf's Up: Season 6 Episode 3Surfing 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 - IntroductionHost 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 3This 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 BiopsyYukti 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 CareGlobal 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 ReportRoger thanks listeners quoting a letter from one of them, and describes the next round of episodes. 

00:00:00 - Surf's Up: Season 6 Episode 2Surfing 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 - IntroductionHost 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 patientsOn 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 monthRoger 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 the exceptional levels of care they achieve.01:08:56 Business Report

00:00:00 - Surf's Up! Season 6 Episode 1SurfingMASH 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 GroundbreakersHost 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 1The 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 ConferenceNow 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 issueOur 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.

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.

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.

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. 

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.

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. 

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 WeekListeners and readers, What do you consider the most essential paper or theme of TLM2024??01:06:38 - Business ReportChanges coming in 2025 with SurfingMASH v2.0

00:00:00 - Surf's Up: Season 5 Episode 25 On July 20, Clinical Gastroenterology and Hepatology released the paper, Expert Panel Recommendations: Practical Clinical Applications for Initiating and Monitoring Resmetirom in Patients with MASH/NASH and Moderate to non-cirrhotic Advanced Fibrosis. Corresponding author Maru Rinella joins the Surfers to share key points from the recommendations and offer her thoughts on what lay behind them.00:02:26 - Introduction and GroundbreakerThe highlight was Louise's groundbreaker: having become a full Fellow in the Roal College of Physicians.00:06:28 - Introducing the paperRoger starts by discussing the importance of this paper and listing the questions the panel will address during the episode. Maru provides a history of developing the paper. Jörn praises its timeliness. 00:08:59 - Treating the "Right" patients; Using the "Right" testsJörh asks why the authors changed the patient definition from a histological one to at-risk MASH patients confirmed by NITs. Maru said the authors sought to follow the FDA guidance on NITs and patient targets. They considered adding liver enzymes or confirmatory VCTE to the protocol, but demurred because not every clinical could execute such a recommendation. Jörn asks whether the authors considered requiring three metabolic risk factors. Roger notes that this question implies a need to prioritize patients, which is a factor in Europe but not the U.S. This paper takes a more U.S-based perspective, which is to set a threshold for use.  00:14:21 - The Decision Not to Discuss CostThe authors did not address costs because they anticipated steep reductions over time. The panel compares the MASH case to HCV. In HCV, the combination of high drug costs and large number of warehoused patients drove prioritization over time. 00:16:34 - Relative paucity of warehoused MASH patients Maru suggests relatively few MASH patients are warehoused. Louise asks whether many U.S. insurers are controlling access by requiring liver biopsy. Maru reports she has not encountered this personally and  estimates it might affect ~5% of cases so far. 00:19:05 - Rationale for Patient SelectionMaru explains the rationale for an F2 threshold for patient selection: patients with fibrosis >= F2 show a demonstrable decline in long-term survival. The rationale for excluding cirrhosis patients? Resmetirom is not yet proven to help patients with cirrhosis. Jörn notes, the MAESTRO-OUTCOMES trial is running and will generate consequential data on cirrhosis. 00:22:11 - Value of Stabilizing Disease without ImprovementMaru notes that the paper focused strongly on how to stabilize patients because the drug is safe and stabilization has real-world benefits.. She points out that patient advocates strongly recommend this focus. All this led to the paper's recommendation to discontinue only upon progression.  00:25:12 - The importance of incremental learningThe group agrees that these recommendations comprise a base that will be strengthened over time as individual providers gain experience with the drug. 00:30:06 - Wrapping upPanelists touch briefly on the value of loose discontinuation rules, how patients feel about starting therapy, how to handle drug interactions, and how the paper is used in the US vs. other countries. In closing, the group remembers Stephen Harrison's unique contributions one more time.00:37:55 - Question of the WeekWhich of the paper's two striking recommendations -- using multiple NITs to qualify patients and continuing therapy unless and until a patient shows signs of disease progression -- will have greater impact on how physicians treat patients?00:38:44 - Business ReportSummer schedules, value of the business report, the vault discussion.

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 - IntroductionRoger 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 PetitjeanThis 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 MattMatt 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 MattMatt 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 JeffJeff 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 JeffConcurrently, 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 WeekThe Question of the Week is the first question Roger asks Matt and Jeff during this episode.01:12:58 - Business ReportPreviewing 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.