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Key Opinion Leaders Manal Abdelmalek, Naim Alkhouri, Scott Isaacs and Zobair Younossi join Roger Green to discuss  FDA's approval of semaglutide for patients with non-cirrhotic MASH. This conversation focuses on benefits for patients and ways that having two drugs with different modes of action will change pharmacotherapy choices.

This conversation starts with the group describing the sense of "enthusiasm" and "fulfillment" hepatology drug developers feel to see two drugs approved in the US and many other major changes to come (more drug approvals, FDA acceptance of a path to approval that is not based on liver biopsy). One interesting takeaway is that while the approval of semaglutide will likely change the number of patients treated with MASH pharmacotherapy, the greater impact of this approval will be on public awareness of MASH and the accompanying demand for treatment. In terms of actual drug use, the first major change will come among patients living with obesity but not Type 2 diabetes. Most of these patients previously saw their semaglutide prescriptions rejected for payment by health insurers. However, many of these patients will be living with MASH, and they are likely to see their prescriptions approved. 

Instead, the largest impact may involve increased education and awareness. Scott pointed out that endocrinologists, who frequently prescribe incretin agonists, will have reason to learn how to diagnose and manage MASH in patients they already treat. Zobair noted that an array of companies, starting with pharmaceutical manufacturers and scanning companies, will dramatically increase investments in prescriber and patient education. 

Another important benefit may come in terms of coverage. Scott points out that most patients living with obesity but not diabetes are unlikely to have their semaglutide prescriptions covered by commercial insurers. Those living with non-cirrhotic MASH are likely to have semaglutide covered. A separate but related point: Naim reports that ~30% of the MASH patients he sees are taking an incretin agonist at the time of initial visit.

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00:00:00 - Surf's Up, Season 6, Episode 12
This week's episode is a special three-part roundtable on the implications of the FDA's recent approval of semaglutide. Naim Alkhouri, Manal Abdelmalek, Scott Isaacs and Zobair Younossi join Roger Green in a discussion that focuses less on specifics of pharmacotherapy and more on how having two drugs available will change MASH management in the US.

00:08:45 - Part I: How Will The Semaglutide Approval Affect Patient Treatment and Pharmacotherapy?
The group starts by describing the sense of "enthusiasm" and "fulfillment" hepatology drug developers feel to see two drugs approved in the US and many other major changes to come (more drug approvals, FDA acceptance of a path to approval that is not based on liver biopsy). One interesting takeaway is that while the approval of semaglutide will likely change the number of patients treated with MASH pharmacotherapy, the greater impact of this approval will be on public awareness of MASH and the accompanying demand for treatment. In terms of actual drug use, the first major change will come among patients living with obesity but not Type 2 diabetes. Most of these patients previously saw their semaglutide prescriptions rejected for payment by health insurers. However, many of these patients will be living with MASH, and they are likely to see their prescriptions approved.

Instead, the largest impact may involve increased education and awareness. Scott  pointed out that endocrinologists, who frequently prescribe incretin agonists, will have reason to learn how to diagnose and manage MASH in patients they already treat. Zobair noted that an array of companies, starting with pharmaceutical manufacturers and scanning companies, will dramatically increase investments in prescriber and patient education.

00:25:30 - Part II: How the Structure of Medical Practice Is Likely To Change
Naim states that many hepatologists are currently uncomfortable managing patients on GLP-1 agonists. This will need to change. Manal points out that providers must check for cirrhosis while testing for MASH and understand how to respond. An increase in the number of providers having access to in-office scanning devices will facilitate this process. Zobair states that even if all the related specialists integrate MASH into their practices, the actual patient care demand will require alternate  pathways in which the responsibility for patient care will rest with specialist APPs.

After Naim Alkhouri describes some of the differences between resmetirom and semaglutide in terms of practical treatment decisions, the discussion focuses on why MASLD and MASH will create unique challenges for hepatology practices. Manal views the issue as a matter of time; practices cannot absorb large numbers of new, non-urgent patients. Naim suggests that the real issue is the business question: specialists today do not profit simply from treating patients. Zobair agrees with Naim and notes that the challenge is not unique to hepatology. He expresses the hope that AI and efficient database management will make it easier to target patients, screen, diagnose and treat them.

00:44:17 - Part III: What Happens Next?
In this final section, panelists identify some of the changes they foresee if we are to manage the tsunami of undiagnosed MASLD patients. Many of the comments touch on themes discussed earlier in this episode, but a couple are unique. Zobair states we must remember that the vast majority of MASLD patients will never develop MASH. Manal foresees a more sophisticated approach to selecting pharmacotherapies as prescribers have a broader set of options, each with its own benefits and drawbacks. Scotts anticipates a "paradigm shift" in which endocrinologists view MASH similarly to how they view retinopathy, neuropathy and retinopathy.

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This week's expert interview is with Dr. Emily Andaya, Medical Director of the Cardiovascular Program at Major Health Partners of Shelbyville, IN. She joins Louise Campbell and Roger Green to discuss the American Heart Assocation's CKM initiative, why she believe it should be titled "CKLM" for liver, and how including liver in the CKM scoring system would make it stronger and provide a more robust tool to help improve patients' health. 

Emily begins by discussing her attendance at the American Society for Preventive Cardiology meeting in Boston the previous weekend, where Dr. Christos Montzoros presented a talk proposing that the liver's role in cardiovascular diseases is "equally critical" compared to the kidney and other multi-metabolic co-morbidities. Dr. Montzoros closed his talk by stating that the CKM syndrome description should be changed to CKLM to reflect the importance of the liver, and that the CKLM patient scoring and criteria should reflect this as well.

Next, Emily describes the 0-to-4 scoring system that the CKM initiative has chosen to use and the recommendations that accompany the scoring system itself. The system does not neatly overlay the 4-point fibrosis scoring system or the NAS score, but Emily describes how these might be incorporated into the CKM score. 

The conversation shifts to focus on patient management. Since the original CKM paper was published in 2023, resmetirom had not yet been approved and the paper itself focused more on screening than on treatment. To Emily, adding the "L" to CKM would entail adding resmetirom to treatment protocols as appropriate, and also considering drug combinations that addressed liver disease. Louise takes this issue from the other side, suggesting that every time a provider prescribes a drug to a CKM patient, the potential for negative liver effects should be part of the selection process. Emily and Louise agree that providers and patients should take a holistic approach to therapy for these patients. One benefit: even if a patient has multiple organs affected by multi-metabolic challenges, the provider can educate the patient that there is a single target disease to treat instead of multiple different diseases. As Roger notes, treating 4-5 discrete diseases simultaneously sounds overwhelming, while treating one overarching disease sounds far more manageable.

The conversation ends with a focus on whether we are correctly identifying high-risk cardiovascular patients in the current environment, and how this more holistic focus might improve patient screening and identification.

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Multi-Metabolic Week focuses on the idea that MASLD and MASH are elements in a systemic set of Multi-Metabolic issues. This conversation is the second of two looking at the concept of the "Multi-Metabolic Clinic," a clinic that treats the entire spectrum of multi-metabolic diseases.

This conversation starts by focusing on how the two clinics train other physicians and practices on multi-metabolic issues. The EDOM clinic in Spain is certified to provide nutritional training to other practices across the country, while the newer, smaller Trajectory Health Partners practice provides support on use of FibroScan and, more recently, Velacur from Sonic Incytes. Louise notes how important training is for optimal use of scanning devices, which includes both technical proficiency and knowledge of how to educate and motivate patients using the results of the scans. 

From there, the conversations shifts to focus on differences between treating patients in a conventional practice vs. a multi-metabolic one. The key differences involve length of patient visit and use of allied providers to educate patients more fully. Next, Louise asks whether the clinics have data on reducing the number of patients needing to go to a hospital. EDOM has data while the younger Trajectory has a clear sense this happens but no large-scale practice data to support this sense. 

Louise's last question is to ask how each physician would "sell" colleagues in their specialty on why to set up a multi-metabolic practice. The answers reflect the different specialties in which the physicians were trained originally (endocrinology in Spain, gastroenterology in the U.S.) but have significant common elements. 

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Multi-Metabolic Week focuses on the idea that MASLD and MASH are elements in a systemic set of Multi-Metabolic issues. This conversation is the first of two looking at the concept of the "Multi-Metabolic Clinic," a clinic that treats the entire spectrum of multi-metabolic diseases. 

The core of this episode starts during the weekly groundbreaker exercise, during which our guests began to describe the path that brought them from single-disease specialization to the broader multi-metabolic practice.. Immediately after the groundbreakers, participants describe their clinics today, including patient population and principles underlying their approach to treatment. 

For Karen, the path started in a conventional gastrointestinal practice. A decade ago, she gained certification in obesity medicine. While treating patients for obesity, she came to appreciate the interplay of obesity, diabetes and the other manifestations of multi-metabolic disease. Eventually, she divided her practice and time so that she spent half her time in the GI practice and the other half creating Trajectory Health Partners, a practice focused on overall metabolic health.

For Dr. López, the initial goal was to "re-educate the hypothalamic problem," which he saw as the root cause of obesity and from which all other metabolic issues came. He describes this as "the auto-destruction button" of patients' lives, leading to two causes of death: (1) insulin resistance and related cardiovascular problems, and (2) short-telomere cancers. 

The rest of this conversation focuses on the tests that the two clinics use to confirm MASLD or MASH and their approaches to treating multi-metabolic patients.

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00:00:00 - Surf's Up: Season 6, Episode 11 

This week, we modify our usual episode structure to focus on multi-metabolic practices and constructs. The multi-metabolic practices covered this week are run by non-hepatologists who have chosen to focus on the liver in a broader cardiometabolic context. They include two practices discussed during a two-part roundtable, one run by US gastroenterologist Dr. Karen Jerome-Zapadka and the EDOM practice in Spain, run by endocrinologists. The expert interview is with Dr. Emily Andaya, an internist who helms a cardiometabolic practice in Indiana, US, that focuses on the liver. 

00:14:23 - Roundtable Part I: Groundbreaker and introduction

The core of the episodes started during the weekly groundbreakers, as guests began to describe the path that brought them from single-disease specialization to the broader multi-metabolic practice.. Immediately after the groundbreakers, participants describe their clinics today, including patient population and principles underlying their approach to treatment.

00:26:15 - Roundtable Part II: Tools they use

Guided by Louise, the specialists discuss the devices they use to screen and stage patients and the drugs they use to treat them. One interesting item that emerges is that EDOM relies on a 0-to-4 disease severity classification, but it does not align point-by-point with the 4-point fibrosis scale common in MASH. 

00:40:28 - Roundtable Part III: Training Providers in the Clinics

Louise starts this segment by asking the EDOM team how they train practitioners in their clinic. EDOM trains practitioners in nutrition and technologists in the proper use of scanning devices. Karen comments that one big issue in re-training involves the length of visits: 15 minutes for a typical GI visit vs. 60 minutes for an initial multi-metabolic session and 30 minutes for follow-ups. Along with this, the information gathering technique are different.

00:50:57 - Roundtable Part IV: Patient Health and Wrap-up

Louise asks participants whether and how they have measured the impact the multi-metabolic approach has on patients' health (profound in both cases) and whether they are seeing an increase in HCC. Karen sees a difference among her long-term patients, while EDOM refers patients before their fibrosis reaches cirrhosis stage. 

In the last part of the episode, panelists share perspectives on how their initial specialties fit with the broader multi-metabolic practice and the kinds of impact they can have on patients.

01:12:50 - Expert: Dr. Emily Andaya discusses US initiatives in multi-metabolic health

This week's expert is Dr. Emily Andaya, an Indiana (US)-based internist whose practice has expanded to take on a multi-metabolic focus. She begins by discussing her recent attendance at the American Society for Preventive Cardiology (SPC) meeting in Boston, where she heard a talk by Dr. Christos Montzoros, an endocrinologist and multi-metabolic advocate, who emphasized the importance of incorporating the liver into preventive cardiology's focus. Louise and Emily agree that cardiometabolic focus involves evaluating general, overall health, but Emily discusses how this might require a deeper or broader testing protocol for each target organ. Emily describes the 4-point CKM scale and Louise asks how fibrosis or NAS scoring, as deployed in the MASH CRN system, might be valuable here. This is a far-ranging conversation, but one special point of interest involves the psychological benefit of telling a patient they need to treat one (multi-metabolic) condition, instead of separate heart, kidney, endocrinological and liver conditions, which might feel far more overwhelming. 

01:48:48 - Conclusion

Because Roger is on vacation, there is no business report this week.

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This week's expert is Tim Jobson, Medical Director of Predictive Health Intelligence, a UK-based consultancy. Tim joins Louise Campbell and Roger Green to share an update on PHI's Somerset UK project and other activities. 

The Somerset pilot was designed to help the NHS identify untreated patients at high risk for liver disease and bring them to the office for screening. Tim describes hepatoSIGHT, a tool that "allows clinicians to get their hands on the data and to find patients both for treatment and for clinical trials."  He describes it as standard in Somerset, UK, now, and proceeds to share new data about the patient experience. This is a unique program in that providers reach out to tell individual patients they should visit the physician based on information found in their medical records. Interestingly, patient response is overwhelmingly positive. Louise shares data indicating that 94% of individuals located by the NHS in this manner visited their GPs. Six in ten respondents rated their satisfaction with the process, giving it a mean of 4.8 on a 5-point scale. Tim also shared some preliminary modeling suggesting that sustained use of hepatoSIGHT could increase clinical trial participation as much as 50-fold if trial sites had the capacity to take all these patients. 

Based on the results of the pilot, hepatoSIGHT is now standard throughout the Somerset region and is being evaluated for broader use. Tim and Louise both point out that this represents a major advance in the applied use of preventive hepatology. In all, this is a warming, affirming look at whether and how patients know they benefit from what we ask them to do and share.   

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Roger Green talks with LiverRight CEO Brandon Tudor and Chief Medical Officer Alexander Lalos about the launch of LiverRight, America's first virtual hepatology clinic, which has recently begun treating patients.

Brandon starts the conversation by telling the story of how he and his partner, Pete Celano, started LiverRight: they saw liver disease as a growing disease in a medical system that was ill-equipped to provide front-line care. When the two men "secret shopped" getting doctor's appointments, they found extremely long waits (3-5 months in examples provided throughout this conversation) for appointments that put stress on the patients and their schedules (days off from work, hours of travel to the clinic). Brandon gave one example in Arizona, where LiverRight could get a hepatologist certified and accepted by insurance months faster than the patient could get an appointment at a local hepatology center. 

Al amplifies the issue by noting that when the patient in Arizona was scheduled to see a transplant hepatologist, who certainly could treat the patient but was "not really appropriately matched to [the patient's] condition. To Al, who is a transplant hepatologist himself, the virtual approach provides three benefits: convenience, speed and a better match between provider and disease. As Al notes, transplant hepatologists spend their time doing transplants, an important and highly specialized skill. A far broader swath of providers could treat a patient seeking testing for MASLD. 

Al notes two more benefits he sees with virtual clinics. After online triage during the initial visit, the patient is routed to the level and type of provider best matched to that individual's need for care. The second benefit, which Al says "may sound crazy," is that an online visit, where the provider is looking directly at the computer (and patient) while entering information, feels far more personal than an in-person visit where the provider is looking at the computer monitor instead of the patient. 

The rest of the discussion covers various advantages that the LiverRight executives believe accrue from virtual care. The most important, in Brandon's words, is that virtual "allows us to move to a preventive world instead of a reactive world." One that Al mentions is that the quality and breadth of knowledge of the virtual providers is higher than he expected and leads to both guidelines that are appropriate to task and special knowledge in key areas such as nutrition.

NOTE: Roger Green is a paid advisor to LiverRight

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This conversation is the first segment of SurfingMASH’s July discussion of key events from the first six months of 2025. Co-hosts Jörn Schattenberg, Louise Campbell and Roger Green each chose one topic of personal interest.  Today, Jörn Schattenberg discusses two recent papers that demonstrate differences in how individual patients respond to different proteomic tests and what this can mean for individualized treatment plans. 

Jörn begins by citing Modulation of megabolic, inflammatory and fibrotic pathways by semaglutide in metabolic dysfunction-associated steatohepatitis, a paper from researchers at Novo Nordisk that Nature magazine posted online on July 21. In this paper, the researchers utilized proteomic testing (aptamer-based SomaSignal NASH tests) to determine whether semaglutide successfully addressed different NAS score elements: steatosis, lobular inflammation, hepatocyte ballooning and fibrosis. The proteomics-based tests indicated an improvement in all four of these elements, but the elements that improved and the amounts of improvement varied among individuals. To Jörn, this suggests that we can use an individual patient's proteomic results to tailor individualized therapy based on the areas in need of improvement, so that the prescriber would know whether the best approach to resolve NAS and reduce fibrosis was one that focused on metabolic issues vs. specific anti-fibrotic effects in the liver. He supports this idea by referring to a paper he had published in JHep Reports. In this paper, he and his colleagues looked at semaglutide Phase 1 and 2 obesity trials, where MASLD was not a criterion for entry. However, analyzing individual patients with the SomaLogic panel revealed that many had some form of MASLD and that semaglutide therapy could resolve the specific MASLD issues. 

The rest of the conversation focused on Jörn's conclusion and the potential for tailoring treatment plans to the individual. Lousie hailed the entire concept as extremely helpful not only in selecting a pharmacotherapy but also in providing patients with information they could use to improve their health further. Roger suggests that the kinds of proteomic tests Jörn describes can lead to first-line multi-agent pharmacotherapy to address the disease with agents that collectively will address the individual patient's profile. 

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00:00 - Surf's Up 6.10.1
This conversation covers three topics. Jörn Schattenberg discusses two papers that suggest an exciting role NITs might play in future prescribing decisions, two executives from LiverRight describe the U.S.'s first virtual liver clinic, and Tom Jobson of Predictive Health Intelligence updates us on how simple analyses of large data bases can identify and motivate high-risk liver patients to visit their doctors. 

00:17:30 - Roundtable: NITs might help physicians determine the value of metabolic vs. specific anti-fibrotic effects for individual patients

The overall theme of this roundtable is "Major Stories and Events of the First Half, 2025." Jörn's contribution is to discuss two papers that use proteomic analyses to determine the degree to which a patient's MASH is driven by metabolic issues as compared to direct fibrotic challenges. Today, when we have only a few drugs, limited NITs and no proteomic tests available for use in practice, these findings point to directions for future research and test development. Over time, providers may be able to prescribe based on the knowledge of h0w much benefit metabolic agents might provide as compared to anti-fibrotics. This may point to step therapy or multi-agent first line therapy, but it is an exciting idea.

00:29:50 - Newsmakers: LiverRight opens America's first virtual liver clinic 

LIverRIght CEO Brandon Tudor and Chief Medical Officer Alexander Lalos join Roger Green to discuss the launch of America's first virtual hepatology clinic. Brandon shares his personal history to explain why providing fast access is so important to him. Alex describes his original motivation to go into Transplant Hepatology and how, over time, his focus has shifted from healing the sick to preventing disease in the first place. They describe how LiverRight works and their successes to date in reducing patients' time from first contact to visit, often from months to days. NOTE: Roger Green is a paid advisor to LiverRight.

00:56:44 - Expert: Tim Jobson describes how Hepatoscope is helping the NHS identify untreated high-risk liver patients and bring them to the office for screening. Tim describes hepatoSIGHT, a tool that "allows clinicians to get their hands on the data and to find patients both for treatment and for clinical trials."  He describes it as standard in Somerset, UK, now, and proceeds to share new data about the patient experience. This is a unique program in that providers reach out to tell individual patients they should visit the physician based on information found in their medical records. Interestingly, patient response is overwhelmingly positive. Six in ten respondents rated their satisfaction with the process, giving it a mean of 4.8 on a 5-point scale. Tim also shared some preliminary modeling suggesting that sustained use of hepatoSIGHT could increase clinical trial participation as much as 50-fold if trial sites had the capacity to take all these patients. In all, this is a warming, affirming look at whether and how patients know they benefit from what we ask them to do and share.   

01:29:58 - Conclusion

The business report discusses the next few episodes and asks who would like to meet Roger at Paris MASH.