Surfing the Nash Tsunami

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.

This week, Surfing the MASH Tsunami looks back on interviews Roger Green conducted during the EASL Congress itself. This conversation with SurfingMASH co-host and Tawazun Health Founder and Clinical Director Louise Campbell took place on the last day of the Congress.This conversation centered on three major topics addressed at the EASL Congress, each of which made Louise "quite enthusiastic."The first of these was the presentation of the new EASL/EASD/EASO Clinical Practice Guidelines and their practical implications (Season 5 Episode 21). Louise described this session as having "blown her mind" with its forward-thinking style and recommendations. She termed it a "leap of faith" that we all need to think differently about diabetes and obesity given how quickly incidence is growing. Her favorite items? The guidelines mentioned resmetirom even before it was approved in Europe.   Also, the guidelines described ways to use several drugs that have not been approved for MASLD to treat patients with other metabolic conditions that are linked to MASLD. Louise also expressed enthusiasm at which three organizations partnered on this document.Roger suggested that this aligned broadly with the various drug presentations in the Late Breaker and General sessions. Collectively, those presentations highlighted an array of drugs with different modes of action and strengths across the metabolic continuum.  More generally, the two agreed that we are looking at a world where, in just a few years, we will have multiple drugs, most with unique modes and all with specific patient targets.Roger asked whether Louise believes that over time, the diagnostic focus would stay with liver stiffness and CAP or switch to in-office PDFF. Louise suggested that in a world where clinical trials may not require biopsy, it would be difficult to build a sufficiently robust data set for any new tests.

This week, Surfing the MASH Tsunami looks back on interviews Roger Green conducted during the EASL Congress itself. This conversation with SurfingMASH co-host and Tawazun Health Founder and Clinical Director Louise Campbell took place on the first day of the Congress.Roger's first interview with Louise took place at the end of Thursday, the opening day of the formal Congress and the first day of research presentations and posters. She starts by describing the "really nice vibe" of the meeting, dampened by the fact that Stephen Harrison was not there, and is no longer with us.The first session Louise chose to discuss was the previous day's Patient Advocate session. To her, the key point was to learn a key question that every provider should share with every patient once a year. She mentioned briefly the one presentation from the day's General Session she was able to attend, a retrospective analysis of the predictive value of VCTE.Next, Louise discussed two sessions she attended that delivered powerful, somewhat novel messages. The first was a symposium sponsored by Novo Nordisk that looked at using the liver "to manage cardiometabolic side" through the liver "rather than focusing on liver disease." The second was the "Healthy Livers, Healthy Lives" presentation that presented "very startling figures" about healthcare costs and lack of productivity in the US and how and why India has targeted this disease aggressively. After Louise and Roger both commented on the building momentum in MASLD and mentioned why they believe this is happening, Louise noted how many conversations about AI and quicker population detection were occurring despite the lack of ability to act on these today. This let Roger recall his major takeaway from the Preview episode (S5 E17), which was the emerging importance of data development and large datasets. He mentioned a paper from the Karolinska Institute that Hannes Hagstrom discussed in that episode.

This week, Surfing the MASH Tsunami looks back on interviews Roger Green conducted during the EASL Congress itself. This conversation with Fatty Liver Alliance Founder and CEO Mike Betel took place Wednesday of Congress week, a day for special sections and industry presentations, but one day before the General Session opened.The first part of the conversation centered  on the Patient Advocate session that Mike chaired with Shira Zelber-Sagi. (This is the focus of Season 5 Episode 23.) The goal of this session was to discuss barriers to addressing unmet needs in a clinical setting and explore potential solutions. He listed the speakers and their topics, and then went straight to his key takeaway: patients around the world are having challenges getting personal attention and time from their treaters. He mentions one panelist who once told a doctor, "I know you're listening  but you're not hearing me." The conversation also touched on stigma and how it comes into these discussions.The rest of this interview touched briefly on the Opening Session and a couple of industry-sponsored sessions Mike attended. His final point was to emphasize the exceptional opportunities for networking at an event like this one.

This week's vault comes from our first episode with Shira Zelber-Sagi. She and Ken Cusi joined us during US Thanksgiving Week 2022 to discuss nutrition and behavioral issues related to MASLD. The episode's original writeup explains:Surfing the MASH Tsunami hosts its first episode dedicated to nutrition and NASH with distinguished guest, Prof. Shira Zelber-Sagi. Alongside this rich discussion are Ken Cusi, Jörn Schattenberg, Louise Campbell and Roger Green.This final conversation starts with Jörn  recalling Shira's statement that “diet is every day.” He notes that for patients whose serious medical issues are related to poor diet and lifestyle choices, behavior and diet can play an integral role in improved patient self-care and overall health. Roger highlights that a combination of medications and self-management can be a powerful, reinforced and effective treatment solution. This leads Shira to provide a step-by-step vision of how to work with patients on improving bad habits. In the end, she notes, clinicians and leaders need to appreciate the importance of policy in supporting clinical goals. The conversation continues with the group discussing what Louise calls “fun facts” about common unhealthy foods. For the final question, Roger asks the panelists for one piece of advice to be utilized by providers seeking to push behavioral change in their patients. Surf on for their key takeaways. 

Co-chairs Shira Zelber-Sagi and Mike Betel and panelists Tom Marjot and José Willemse, all from the EASL Congress session "Patient Experiences in Clinical Settings," join Louise Campbell to the need for resources that allow MASLD patients to access shared experience programs and holistic MASLD support programs. This final conversation focuses on shared experience and holistic MASLD support programs. It starts with Tom suggesting that shared experience is a pivotal factor in patient support groups and patient-based supportive care. He goes back to viral hepatitis, where many of the patients had common background challenges related to the disease. In viral hepatitis, patients who have been treated successfully become integrated into the care community. Nothing like that happens in MASLD at this time. Louise comments this would be particularly useful due to stigma around the disease, stigma that successfully treated patients have overcome.  Louise points out that Michael makes extensive use of shared experience videos, such as this month, when he invited patients to follow him on a "30-day glucose challenge." Michael says that he gets unsolicited notes about how helpful the approach is, along with diet recipes. He agrees with Tom that a viral hepatitis model might provide help here.  Mike discusses the idea of metabolic disease support programs that take a more holistic approach and place MASLD in a broader, multi-disease context. Shire likes the holistic approach as well, including a focus on mental health. Tom agrees with the basic approach, commenting that the multitude of possible issues is what makes MASLD so tricky.  As the conversation wraps up, two final themes emerge: (i) physicians must be actively curious in exploring each patient's needs if therapy is to succeed, and (ii) joint goal setting is an excellent strategy for driving incremental changes in behavior.  

Co-chairs Shira Zelber-Sagi and Mike Betel and panelists Tom Marjot and José Willemse, all from the EASL Congress session "Patient Experiences in Clinical Settings," join Louise Campbell to discuss ways that socioeconomic and psychological issues impact the dynamic of the physician-patient consult, and, as a result, often patient adherence to therapy.This conversation starts with Shira asking Tom whether he addresses diet with his patients and, more importantly, whether he does so in the context of socioeconomic challenges, such as not recommending food that is too expensive for the patient. Tom says "Yes" to the first part, about diet and nutrition discussions and encouraging all patients to adopt a more healthy lifestyle, but, he says, not enough about socioeconomic issues. He feels that may be changing, though, based on the increasing discussion of food insecurity at conferences. The two agree that sensitivity in the topic is growing and needs to grow more in the years ahead, and also that while they are tailoring their discussions to address these issues, they can do more. Shira has begun to simplify her recommendations: fewer foods and less preparation time. Tom agrees this is a good idea.  Tom notes that he is focusing more these days on unemployment, social isolation and what he describes as social "unmet needs." He cites figures that 80% of the patients in a liver clinic have unmet needs and that improving social engagement can affect health. Mike asks whether the providers consider mental health, particularly given how important behavioral support is to treatment. Does Shira or Tom recognize mental struggle when the patient is sitting in front of them? Tom says this is an excellent question and identifies the three items patients in large studies say they seek in this realm: (i) education, (ii) reduction of stigma, and (iii) better psychosocial support. Mental health challenges are linked to unmet needs which, again, are linked to poor liver health. Tom believes the UK system does a good job of identifying this issue at the primary care level. Shira agrees this is important and, in her case, involves using quiet, probing questions in a sympathetic tone.   Louise asks whether Tom or Michael have observed MASLD-specific patient support groups in their regions. Both report that there are liver support groups, but nothing yet as specific as MASLD. 

Co-chairs Shira Zelber-Sagi and Mike Betel and panelists Tom Marjot and José Willemse, all from the EASL Congress session "Patient Experiences in Clinical Settings," join Louise Campbell to discuss strategies and questioning styles that can improve the dynamic of the physician-patient consult.This conversation starts with Tom stating that having multidisciplinary treatment teams would provide tremendous benefits in terms of being prepared for patients and fully responsive to the issues they are likely to raise. Jose agrees but adds that many countries have only a few nurses and no ability to create these kinds of teams.  Shira states that every physician should learn the principles of motivational interviewing. The key to this is asking open questions that allow the patient to respond fully without feeling judged or steered in a specific direction. This enables the patient to share unhealthy behaviors, which they might not do if the physician admonished them in advance. Tom agrees with the positive tone, saying that so much of the physician's role is all about trying to enthuse the patient to take control of lifestyle factors.  Along a similar theme, Mike notes the importance of tailoring care and questions to the individual patient. He points out that while 10,000 steps/day might be a goal, for some patients, it will feel so unattainable as to be demoralizing. Shira points out that an open question would start by asking the patient what goal is reasonable, and Jose follows by sharing an example of a patient who "hated" all exercise. José found a way to motivate the patient with simple, timely reminders that this was for the liver, and that the liver would be appreciative.  Louise adds that changes in activity if the patient can define them as "fun."

Co-chairs Shira Zelber-Sagi and Mike Betel and panelists Tom Marjot and José Willemse, all from the EASL Congress session "Patient Experiences in Clinical Settings," join Louise Campbell to discuss some of the key dynamics shaping the physician-patient consult.This conversation starts with Mike asking Tom whether he reviews the patient's history before the visit. Tom says he does so because he considers preparation vital to a successful consult. That said, Tom notes the importance of being responsive to the conversation rather than using the chart review to decide the outcome of the visit. He provides some empathetic detail about how important the visit is to the patient and, as a result, how important that he be responsive as well as prepared.  José agrees, provides more color, and notes what she considers the most important question a physician can ask a patient: "How are you feeling today?" To José, asking that question just one time a year can change he entire dynamic of the relationship.  Tom then notes the scarcity of time and the double-edged demand this creates for each visit: plan in advance to use time as productively as possible, but once the patient is in the consult, give it all the time it needs.  After José makes a point about the importance of using language precisely, Louise joins the conversation to describe the consult as "like speed dating," with both sides having a scare few minutes to make a relationship that will be pivotal to the patient. 

Co-chairs Shira Zelber-Sagi and Mike Betel and panelists Tom Marjot and José Willemse, all from the EASL Congress session "Patient Experiences in Clinical Settings," join Louise Campbell to provide an overview of issues in physician-patient communication. The conversation itself has two elements. It starts with first-time surfers Tom Marjot and José Willemse introducing themselves to listeners. After that,  Shira starts by discussing the EASL Congress session within the context of a broader collaboration called "EASL Patient Synergies." This program led to the creation of the Patient and Advocate Forum as the EASL Congress, which led to this program. She says this year's program "worked" in developing "very interesting and fruitful and open dialog between patient and patient representatives and physicians," focusing on unmet patient needs and the roles various providers can play in addressing these. Mike shares one of his key takeaways: how fearful patients are when approaching physicians and how little information they share.   Mike recalls a comment Tom made during the session that if a patient ever told him, "What you just said hurt me or made me feel bad," that would have more impact on him than, as Tom puts it, "an entire weekend at a stigma workshop." Tom describes three levels at which to address patient stigma. Two of these, public policy and patient advocacy, are well known, but the third, improving direct physician-patient interaction, may be more vital and is underappreciated today. If patients provided direct feedback to Tom when Tom was communicating poorly, he says, he could adjust with the very next patient. Today, though, he doesn't get that kind of feedback.   Jose sees this as a two-way problem. Yes, most patients are fearful and do not share what they are thinking with the provider, but the reverse is true as well. When a patient shares feelings with a provider, the provider may not be equipped to handle it. She makes this point about provider insensitivity or failure to listen with two powerful vignettes.  Tom recalls Jose telling him in Milano that when the physician turns off the computer screen, it changes the entire dialogue with the patient. He has begun to do so, and it works!  Jose makes a couple of points about this. First, simply asking that patient, "How do you feel?" and engaging with the answer makes the patient more satisfied with the visit. Second, this speaks to the idea that physicians do not realize how important they are in the lives of their patients. 

00:00:00 - Surf's Up: Season 5 Episode 23 During SurfingMASH's wrap-up interviews from the EASL Congress (S5 E19), Louise Campbell and Mike Betel mentioned a session Mike co-chaired on challenges in provider-patient communications. Today, the other co-chair, Shira Zelber-Sagi and panelists Tom Marjot and Jose Willemse join Louise and Mike to return to this topic.  00:13:34 - Discussing the EASL Congress sessionShira describes EASL Patient Synergies, a broad collaboration to develop open, solution-centered dialog focusing on what patients need in working with providers. Mike shares a key takeaway. 00:16:31 - Stigma in what doctors say to patientsThis section covers the issue of physician saying things they do not realize patients find hurtful. If the patient would share their discomfort, the provider could adapt on the fly. Jose sees this as a two-way problem: patients do not share feeling, but when they do, most providers cannot handle them. 00:19:40 - Sending signals of attentivenessThis section covers the positive impact when the physician does something simple like turning off the computer screen and the reasons why.00:21:06 - Preparing for a patient consultTom considers prior preparation and chart review vital to a successful consult. Panelists note how much more important the consult is to the patient compared to the provider.    00:29:23 - Structural improvements for patient consultsTo Tom, multidisciplinary treatment teams provide tremendous benefits in patient preparation and responsiveness, but Jose notes that many countries lack the number of nurses necessary to do so. 00:30:57 - Motivational InterviewingShira suggests that every physician learn the principles of motivational interviewing: asking open questions with no emotional valence. This enables the patient to share unhealthy behaviors. The panel agrees, noting that physicians can motivate and that they are most effective when tailoring to the individual.00:38:10 - Food insecurity as risk factorShira asks Tom whether and how he addresses diet with his patients and, more important, he does build socioeconomic factors into the decision analysis. Tom says "Yes" about diet and healthy lifestyle, but, he says, not enough about socioeconomic issues. They agree that awareness of the impact of food insecurity  is growing and needs to grow more. 00:41:10 - Assessing mental health and quality of psychological life The group considers the idea that a large majority of patients in a liver clinic have unmet economic or mental health needs, and discusses what to do to improve social engagement.  Tom identifies the three items patients in large studies say they seek.  The group discusses the idea that they see liver support groups, but  none are MASLD-specific. 00:46:03 - The value of lived experience in providing careThis section explores shared experience as a pivotal factor in patient-based supportive care, similar to viral hepatitis, where successfully-treated patients become integrated into the care community. 00:49:03 - Holistic metabolic disease support programs and wrap-upMike suggests that MASLD support programs take a more holistic approach that places MASLD in a broader context. Shira suggests adding a focus on mental health.  As the conversation ends, two final themes emerge: (i) physicians maximize success by being actively curious in exploring each patient's needs; and (ii) joint goal setting is an excellent strategy to drive behavior change.00:54:41 - Question of the WeekWhat structural or educational changes do you anticipate will improve provider-patient communication significantly, and will these changes require more from the provider, the patient or both?00:55:14 - Business reportInformation on future episodes plus a shout-out to Indonesia. 

In this week's episode, Jeff Lazarus discusses the idea that the MASH community, including patient advocates, live in a "bit of a bubble," where the clinicians with whom they interact are part of the MASH community. Last year's ICER Public Comments session exposed them to an FDA Advisory Board of hepatologists...and it was a very different experience. Last year's conversation notes reveal what happened and the advocates' reactions:In March 2023, Jeff McIntyre (GLI) introduced a draft report from the Institute for Clinical and Economic Review (ICER) on resmetirom and obeticholic acid for NASH. The Surfers dedicated an episode to expand on the contents, its shortcomings and potential implications with special guests Veronica Miller (Liver Forum) and Hannah Mamuszka (Alva10). In this conversation, SurfingMASH revisits the topic after a public comments session that took place last week. In doing so, patient advocates and friends of the podcast Mike Betel (Fatty Liver Alliance), Tony Villiotti (NASHkNOWledge) and Wayne Eskridge (Fatty Liver Foundation) join co-hosts Louise Campbell and Roger Green to share a range of impressions.Roger begins by asking the group how the word empathy fits into this discussion. Tony shares that he was upset by the majority viewpoint of 15 featured voting members on a number of different issues. For example, 40% of these voting members suggested that a drug approval would have no impact on a caregiver's life. Tony asserts the importance behind people needing to be aware of the impact of NAFLD/NASH not only on the patient, but also the families and those close to them. Speaking from personal experience, Wayne shares that he was perplexed on the document's position that NAFLD/NASH is not considered to be a progressive disease. This leads Louise and Roger to insert comments around the pricing and economic analysis surrounding the discussion. As the conversation winds down, Mike returns to the conundrum of the voting results. Listen on to hear why his reaction was, “I literally fell out of my chair.”

In this closing conversation, Healthy Livers, Healthy Lives Chair Jeff Lazarus and Surfers Jörn Schattenberg, Louise Campbell and Roger Green discuss the upcoming United Nations General Assembly side event and consider ways listeners can support the "Healthy LIvers, Healthy Lives" coalition.Jeff discussed this impact on global care when the World Health Organization develops and releases a global health sector strategy. One key goal in public health is to lobby for a MASLD strategy. To that end, Healthy Livers, Healthy Lives is holding a side event at the United Nations General Assembly meeting in mid-September.  00:40:41 - Presenting MASLD to politicians One challenge in educating policymakers about MASLD is that people do not die from MASLD. One recent example: policymakers did not respond to the spread of SARS-CoV-2 until COVID-19 produced massive numbers of deaths. When asked, Jeff draws the chain from MASLD to MASH to cirrhosis and end-stage liver cancer and notes that we are already seeing MASLD as a leading cause of liver transplant. Roger suggests that Jeff reframe the issue to be about how many people die with MASLD, not from MASLD. Jeff believes this simple change may change the dialogue.  00:43:06 - How listeners can support this initiative Roger asks Jeff how listeners can support the Healthy Livers, Healthy Lives initiative. Jeff suggests that we all be careful to name the disease and let people know how easily MASLD can be identified and treated. For those who work in related areas or help set policy for their organizations, make sure that MASLD is included and, whenever possible, linked to diabetes, obesity, and other relevant metabolic conditions.   00:44:58 - LiverAIM and exit. As his closing comment, Jeff discusses LiverAIM, the largest European Commission-funded liver project in 26 years. (Jörn and Maja Thiele, who is leading the 100,000-person randomized clinical trial, discuss this in Episode 15.) Roger commits to producing an episode on LiverAIM this fall.   After Jeff departs, Jörn restates the importance of working with colleagues like Jeff who can systematically develop public health approaches and drive policy change from the top down. Roger agrees that a top-down approach can be extremely valuable, but may have limits in primary care. He suggests that professional organizations also need to bring allied health providers into the dialogue. 

Healthy Livers, Healthy Lives Chair Jeff Lazarus joins Jörn Schattenberg, Louise Campbell and Roger Green to discuss the value of the updated EASL/EASD/EASO MASLD clinical practice guidelines and consider the role of Big Data in early MASLD screening. Roger asks Jeff whether he considers the updated MASLD CPG a step forward. Jeff praises the guidelines as "amazing" and suggests that one reason is that EASD and EASO are partners in drafting and promoting them.Roger's next question to Jeff addresses the idea that Big Data can provide a set of common variables that will outperform FIB-4 in predicting which patients are at high risk of MASLD or MASH, as Hannes Hagstrom discussed in Episode 17 this year. Jeff believes we can use more data than only the FIB-4 today but that, in the long run,we need better biomarkers to simplify the system. Jörn adds that having historical blood tests will allow for that kind of analysis, which should be superior to FIB-4. Jeff points out the challenge: not all variables are collected in each country. Bottom line: the solution must be simple and realistic to apply in practice in different countries.  

Healthy Livers, Healthy Lives Chair Jeff Lazarus joins Jörn Schattenberg, Louise Campbell and Roger Green to discuss some of the specific structural challenges that confront global MASLD public policy, along with some promising local activities. Louise observes that, in her experience, primary care practitioners appreciate the support that specialist nurses can bring in educating providers about the disease and patients about how to better support themselves. Jeff responds that these are good findings as individual cases, but to make major changes in the field, we need large-scale, top-down innovations. One thing that, oddly, works in MASLD's favor is that most patients with advanced MASLD will have concomitant diseases requiring involvement with other specialties. Today, teams are looking at system issues to find the largest, most intractable structural problems so that solutions can emerge. After that, "we'll start to see bigger and faster improvements in the field." Jeff talks about several positive things happening in New York. First, he mentions a New York Times article about junk food and how manufacturers target aggressive marketing to poor and marginalized populations, with the net result that these populations have processed and ultra-processed foods making up a large share of their diets. Also, a "visionary" health commissioner is creating a program, Healthy NYC, with the goal of increasing life expectancy by reducing specific diseases.MASLD is not part of the effort today but with clinician support. we can get there over time. Earlier, Jeff had commented about the ease of implementing the FIB-4 test. Now, Roger raises the issue again, this time mentioning that SurfingMASH guests from ex-US markets have mentioned that ALT is not a standard test in their countries and asks Jeff if MASLD is making progress here. Jeff discusses the debate around this issue.  

Healthy Livers, Healthy Lives Chair Jeff Lazarus joins Jörn Schattenberg, Louise Campbell and Roger Green to discuss why political will is so important in overcoming inertia and obstruction in global MASLD public health policy.Louise notes that she left NHS because of obstruction against earlier stage efforts to promote liver health and asks how to achieve these goals. To Jeff, it all depends on political will. He provides an example from viral hepatitis to prove his point.Roger asks how to motivate primary care practitioners who are overloaded with tasks they need to complete during short, overly scheduled patient visits.Jeff notes this is a challenge today, with a solution that lies in education that not only teaches about the disease but also stresses the cost of inaction. To Jeff, teaching FIB-4 to primary care and automating the algorithm to make it available in every electronic patient record is the minimum we should strive for today.Jörn focuses on the cost of inaction from a different direction: physicians who are afraid they will demoralize patients when they diagnose a disease with no available treatment. Jeff responds, "Do we not raise awareness because we don't have out-of-the-box solutions?" He goes on to describe different types of solution that might work for a patient, ranging from digital apps to linking patients to social agencies that can provide support and services. Jeff notes that "the field will need to change as we find more patients," due to increased demand on public health systems and social agencies.

Healthy Livers, Healthy Lives Chair Jeff Lazarus joins Jörn Schattenberg, Louise Campbell and Roger Green to discuss how the coalition came into existence and to describe two initiatves aimed at increasing early screening.Jeff starts the conversation by describing the "bit of a bubble" in which the MASLD community lives: great news and lots of excitement within, but very limited exposure to related metabolic specialties (endocrinology, primary care, cardiology) and limited awareness among the people and organizations that shape public health policy.Jörn adds that Jeff has been working for the last 4-5 years to create a multi-stakeholder coalition to promote liver disease to relevant professional societies and public health policy shapers. Jeff notes that patient advocates, clinicians, and professional societies each have a pivotal role to play in advancing liver care, particularly MASLD care.Healthy Livers, Healthy Lives is a coalition of four major professional organizations (AASLD, ALEH, APASL, and EASL) along with other partners, like the Indian National Association for the Study of the Liver (INASL), to raise awareness within the liver field and also other metabolic specialties. Jeff describes it as  "really trying to be an open, transparent, engaging, ambitious and aspirational coalition" with a light structure and just a few areas of focus over the next year: World LIver Day on April 19, the World Health Assembly, and the UN General Assembly.Louise asks about efforts to promote early screening that will help patients get care earlier in their disease progression. Jeff mentions two: a project to "double the diagnosis" over the next 3-4 years, and another project to identify all the concomitant conditions with sufficient cost of disease to merit screening everyone in that group. The latter will provide the kind of data to which public policy makers respond best.

00:00:00 - Surf's Up: Season 5 Episode 22  Jeff Lazarus joins Jörn Schattenberg, Louise Campbell and Roger Green to discuss Healthy Livers, Healthy Lives, a coalition of four major professional organizations (AASLD, ALEH, APASL and EASL) and other partners. This coalition works with other specialties to create global public health awareness and drive "top-down" solutions that are pivotal to stemming the MASLD Tsunami.  00:06:48 - The need for a MASLD public health coalitionJeff starts the conversation by describing the environment in which the MASLD community lives today: great news and energy within, but minimal exposure among related metabolic specialties and public health policy shapers. 00:11:55 -  Healthy Livers, Healthy LivesJeff describes the structure and goals of Healthy Livers, Healthy Lives.00:13:32 - Two initiatives to increase early screeningIn response to a question from Louise, Jeff mentions two efforts: a project to "double the diagnosis" over the next 3-4 years and another to identify all the concomitant conditions with sufficient disease cost to merit screening everyone living with that condition. 00:16:39 - Political will and structural changeLouise asks how we can overcome obstruction within the system to promote liver health. To Jeff, it all depends on political will, the energy that converts successful localized strategies into large-scale, top-down innovation. The solutions to the most significant, most intractable structural problems that evolve this way can drive "bigger and faster improvements in the field." 00:28:40 - Good things happening in New York In this context, Jeff shares how a visionary health commissioner in New York has created the Healthy NYC program to increase life expectancy by reducing specific diseases. 00:33:00 - The updated MASLD CPGJeff praises the updated MASLD CPG guidelines as "amazing" and suggests that one reason is that EASD and EASO are partners in drafting and promoting them.00:35:40 - Big Data-drive screening solutionsThis section explores whether and how Big Data can provide a set of standard variables that will outperform FIB-4 in predicting MASLD risk (see S5 E17). Jeff and Jörn identify the benefits and challenges of this approach.  00:38:38 - The upcoming U.N. General Assembly MASLD side eventHealthy Livers, Healthy Lives is holding this event at the U.N. General Assembly meeting in mid-September. The goal is to push the World Health Organization to develop and release a global health sector MASLD strategy.   00:40:41 - Presenting MASLD to politiciansOne challenge in educating policymakers about MASLD is that people do not die from MASLD. Sadly, large death counts produce public sector action, as we all saw with COVID-19. Suggestion: Reframing the issue as to how many people die with MASLD, not from MASLD, may make the story easier to tell.   00:43:06 - How listeners can support this initiative Roger asks Jeff how listeners can support the Healthy Livers, Healthy Lives initiative. Listen to hear Jeff's suggestions.   00:44:58 - LiverAIM and closing comments Jeff mentions LiverAIM, the largest European Commission-funded liver project in 26 years (see S5 E15). Jörn restates the importance of working with experts in developing public health approaches that drive policy change from the top down. Channeling Louise, Roger suggests that professional organizations need to bring allied health providers into the dialogue.   00:50:03 - Question of the Week Roger asks what listeners believe they can do in their own organizations and lives to support the goals discussed today.  00:50:36 - Business Report News on next week's session, Roger's office hours, and the Vault conversation.

This week's vault conversation looks back 17 months when Ken Cusi joined co-hosts Louise Campbell, Jörn Schatenberg and Roger Green to discuss the revised AASLD Practice Guidance that had been issued the previous week. At the time, here was SurfingMASH's summary of the conversation: Late last week, AASLD published new practice guidance on the clinical assessment and management of NAFLD. The Surfers convene with Ken Cusi, who contributed to the previous iteration published in 2018, to explore its key features and implications. The updated document reflects the many advances pertinent to any practitioner caring for patients with NAFLD. This conversation focuses on the impact this guidance may have on patients: will it make a difference and if so, how?Ken asserts his position that both patients and providers need to be educated on solutions available today. Measures range from effective diet modifications to bariatric surgery and anti-obesity drugs. Louise Campbell reminds us that not all patients interact with physicians and that nurses, dieticians, and other allied health professionals experience more numerous contact points in terms of co-morbidity management. She asserts that guidances and guidelines need to make an effective impression on the frontline professionals, caretakers and even the patients themselves. This prompts Ken to share some exciting news with regard to the ADA formally recognizing NASH as a problem associated with diabetes. He reveals that he is chairing a committee that will work to create a consensus statement on this subject through consulting an array of stakeholders. Notably, they are inviting the participation of dieticians, diabetes educators, pharmacy representatives, obesity management leaders, primary care representatives and hepatologists, among other groups. Ken expresses his optimism for the momentous energy and convergence of fields in an unprecedented effort to collectively combat Fatty Liver diseases. Jörn adds that such collaboration will drive stronger patient advocacy and better education about what specific questions they should be asking their treaters. 

In this closing conversation, updated MASLD CPG co-authors Frank Tacke and Elisabetta Bugianesi and podcast co-hosts Louise Campbell and Roger Green consider what the guidelines might foretell in changes in provider education, structure of patient visits and treatment in less affluent or medically advanced countries. The last set of questions begins with Roger asking what kinds of changes the authors would like to see in the healthcare system.  Frank likes Louise's idea of cardiometabolic pathological nursing and, more broadly, motivating physicians and nurses to view MASLD holistically. Elisabetta envisions a world where not only are there multidisciplinary teams, but each physician asks what they can do for the "liver/kidney/metabolic alliance." Frank describes this as "like a dream" and would like a world where the patient comes to the hepatologist for a cardiac workout, endocrine workout, nutritional counseling and other holistic support. It would also help get the correct patients triaged in primary care or referred to specialists.  Roger asks whether Tumor Boards in oncology serve as a model for integrated metabolic disease treatment. Frank says in his institution, boards exist for cirrhosis patients but will never be realistic for the number of patients needing treatment. As the episode winds down, several issues emerge. Louise wonders how these guidelines might be used in less affluent countries or those with less advanced/resourced healthcare systems. Elisabetta stresses the importance of generating awareness. Roger asks how the guidelines will incorporate updates for future drugs and bariatric surgery data; Frank feels this will not be a particular challenge and cites the upcoming data on obesity drugs and the SPECIAL study as information that might drive updates. Frank also suggests that all listeners should download the guidelines (the link is listed on the Surfing the MASH Tsunami web page.) And with one final set of congratulations to the authors, the episode ends.  

For most of this conversation, updated MASLD CPG co-authors Frank Tacke and Elisabetta Bugianesi discuss key issues related to pharmacology and prescribing choices. At the end, the focus shifts to the guidelines' overall benefits and some new kinds of education they call for. The conversation starts with co-host Roger Green asking about key issues from the pharmacology section. Frank states that one benefit of the CPG is the clarity around the point that optimal treatment for a co-morbidity must involve thinking holistically about the liver in the overall metabolic context.Elisabetta notes that while no drugs are efficacious for cirrhosis, the document does report that some drugs are safe for these patients, although sometimes with adjusted doses.Frank concurs that the document provides guidance on managing patients with end-stage liver disease and also discusses how to manage cirrhosis and its various complications. Elisabetta notes that these can be the most difficult patients to screen for HCC because "the fat liver is sort of foggy."This leads co-host Louise Campbell to discuss a point that arises frequently on this podcast: the positive value of simply stabilizing disease through medication and lifestyle.Roger adds that many primary care physicians in the US find managing metabolic multi-comorbid patients confusing and frustrating. These guidelines, with an integrated vision of metabolic diseases and the idea that stabilization might be a sound strategy, simplified the perceived task.Louise suggests that these guidelines "pinpoint...a role of the potential future" for nurses who can support the entire cardiometabolic syndrome. As she points out, even hepatology nurses are "not good at fatty liver disease." This document might drive a curriculum for such a specialization.

In this conversation, updated MASLD CPG co-authors Frank Tacke and Elisabetta Bugianesi discuss some of the guidelines' key goals and issues surrounding the screening, diagnosis and management of MASLD patients. As the conversation starts, co-host Roger Green says that he, too, was impressed that all these adjustments were made within a month at the end of the process. Frank praises the "very engaged Delphi panel" that reacted and voted quickly, and fairly consistently.  He proceeds to discuss how the Delphi panel was formed. From here, the discussion shifts into its key focus: patients. Roger asks for high points in the discussion of screening, diagnosing and managing patients. Elisabetta starts by stating that the resmetirom approval is creating a great push for screening because physicians feel that there is something they can do to help their patients. She describes an approach that begins with FIB-4, proceeds to VCTE and offers two paths for patient management. This should help the system identify patients before cirrhosis or HCC in pre-cirrhotic patients.  Frank points out that this set of guidelines does not rely on biopsy for risk assessment, which he terms "a major breakthrough."  Co-host Louise Campbell lauds the document's approach to diet advice, specifically the broad range of diets that will make it valuable worldwide and for primary care physicians to work from.  Frank adds that the guidelines have adjusted thresholds and other "adaptations to the ethnic background of the individual." This included considering the socioeconomic factors of a target country.