Surfing the MASH Tsunami

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SurfingMASH's last year-end interview with Stephen Harrison took place in 2022. Louise Campbell and Roger Green join Stephen to discuss a promising year in MASH drug development and the podcast itself. 

At the time, this was the description of the interview posted in Buzzsprout:

In the Season 3 NAFLD Year-in-Review conversations series, Surfers Jörn Schattenberg, Louise Campbell and Roger Green embark on a string of interviews with a handful of Key Opinion Leaders who made headlines and advances in Fatty Liver disease in 2022. In this exclusive segment, podcast co-founder and former co-host, Stephen Harrison, joins Louise and Roger to discuss the year-in-review as recorded before Madrigal’s breaking announcement of the Phase 3 MAESTRO-NASH results last week.

From the outset, Stephen admits there were “a lot of pleasant surprises” this year, alluding to the multiple positive Phase 2 trial results among other recent press releases. He anticipates several exciting modes of action becoming available in the imminent future. The interview goes on to look at advancements made in methodology of interpreting liver biopsies, understanding the limitations of biopsy and degrees of mitigation in response to those shortcomings. Stephen also offers in-depth investigation into the uptake of NITs as conditional clinical trial endpoints, something he sees as a process whose momentum keeps growing and strengthening.

Throughout this session, Stephen provides speculation as to what the promising new year holds for the Fatty Liver field. In his words, 2022 revealed “the most incremental advances in the field of NASH in the past decade.” He adds that, like this year, 2023 is primed to be pivotal. Surf on for the full-length, insight-laden interview with a remarkable physician and Principal Investigator making tremendous contributions to the pursuit of putting a major dent in Fatty Liver. 

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Manal Abdelmalek and Naim Alkhouri join co-hosts Jörn Schattenberg, Louise Campbell and Roger Green to reflect on the greatest professional accomplishments of co-founder and former co-host Dr. Stephen Harrison.

Naim Alkhouri starts this conversation by describing the two prospective epidemiology papers Stephen co-authored at San Antonio Military Medical Center in 2011 and 2021, an innovative design that provided early estimates of the breadth of MASLD and MASH in an asymptomatic population. He goes on to discuss Stephen's work on FAST and other NITs and finishes by remembering Stephen's exceptional work in drug development, culminating in the recent FDA approval of Rezdiffra. 

Manal Abdelmalek starts her comments  by recalling that Stephen developed the BARD score and, years later, celebrated that it had been supplanted by better tests. After commenting on his impact in drug development, she describes him as "visionary" and says Stephen was "not a one man show. He thought about networks and collaborations and how to move a field forward with speed and agility." 

Louise Campbell also reflects back on the BARD score and the process by which Stephen came to accept that the nomenclature change was a necessary thing. She closes her comments by reflecting on his persistence and innovation in drug development and finishes with a Harrisonisms about the value of failure and learning in the development of the product WD-40.  

Finally, Roger Green discusses how Stephen's desire to tear apart his failures and learn from them resulted in the landmark paper that challenged how biopsies were being read and interpreted in clinical trial design, and also agrees with an earlier comment from Manal about how innovative the original design for Pinnacle Clinical Research was.

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Manal Abdelmalek and Naim Alkhouri join co-hosts Jörn Schattenberg, Louise Campbell and Roger Green to share personal memories of co-founder and former co-host Dr. Stephen Harrison. 

Naim Alkhouri starts the conversation by describing how he met his "friend and mentor," Stephen. He recalls coming to San Antonio in 2017 to work with a different research group and contacting Stephen. Stephen told Naim he had "made the wrong decision" by not joining his team instead. Nonetheless, Naim persisted, and the two began a rich, rewarding friendship and research experience, which Naim describes in greater detail.

Jörn Schattenberg says that Naim's story resonates with him. Stephen "support[ed] younger people in the field," including Jörn when he was starting his career in Germany. Historically, there had been challenges in conducting clinical trials in Germany, but Stephen worked with Jörn to overcome these and create a stable structure and base for conducting MASH trials. Jörn notes that the relationship Naim described applies not only to the two of them, but also to many other young researchers. 

Manal Abdelmalek recalls meeting Stephen in the earliest days of MASH, when a few young researchers shared posters in a "dark corner" of an AASLD meeting. Manal was impressed by Stephen's energy, warmth, curiosity and confidence that what was then called NAFLD would be "big" someday. 

Louise Campbell recalls meeting Stephen in the early days of SurfingMASH and always being appreciative of his support for nurses and allied professionals and the role they play in patient treatment. She goes on to note that the SurfingMASH podcast's growth affirmed the vision that Stephen and Roger Green had when they started the podcast.

Finally, Roger Green shares his story of meeting Stephen at NASH-TAG 2019 and being impressed with how his energy suffused the entire space. Roger goes on to describe the process by which he and Stephen started the podcast and decided to expand its scope.

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Manal Abdelmalek and Naim Alkhouri join co-hosts Jörn Schattenberg, Louise Campbell and Roger Green to rshare some of their favorite "Harrisonisms" - words, phrases and verbal memes associated with co-founder and former co-host Dr. Stephen Harrison.

Naim Alkhouri starts by stating two of his favorite Harrisonisms, two that SurfingMASH listeners know well: "is the juice worth the squeeze?" and "Keep It Simple, Stupid." He goes on to add one that never appeared on the podcast, "FAIL stands for First Attempt In Learning," which he used frequently in discussed failed clinical trials. 

Manal Abdelmalek  shares several phrases she describes as "words to live by." Two of these are "don't you don't take yourself too seriously " and "There will be failures. The worst ones possible are those that you don't grow and learn from." She discusses how human, approachable and down-to-earth Stephen was, and closes with a story about him ordering a hamburger and "American French Fries" at a gourmet restaurant in Paris because that was all he really wanted to eat. 

Louise Campbell shared a Harrisonism she heard for the first time at Stephen's funeral about the difference between wisdom and knowledge: "Wisdom was knowing that a tomato was a fruit, and knowledge was knowing not to put it in a fruit salad." She goes on to comment on the joy he took in living a life of service.

Finally, Roger adds two favorites of his own: "the liver is the canary in the coal mine," and that when Roger heard Stephen ask whether the juice was worth the squeeze, he always followed it with "is the view worth the climb?" Roger goes on to tell a story about Stephen's older brother, Ken, responding personally to every social media post-mortem to Stephen he could find because it is what Stephen would have done, and Ken's comment about Stephen's basic humility and dedicating his accomplishments to "God's glory." 

Finally, Naim tells about story about Stephen's interest in wine and Naim's in shopping and how they merged in a single vignette about Stephen and his daughter Anna Lauren in Paris.

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The sudden passing on April 23 of our co-founder and colleague Stephen Harrison sent shock waves throughout the global SLD community. This week, Manal Abdelmalek and Naim Alkhouri join Jörn Schattenberg, Louise Campbell and Roger Green to remember and pay tribute to an exceptional leader, role model and human being.

00:00:00 - Surf's Up: Season 5 Episode 14
Episode introduction, including brief quotes taken directly from panelists.

00:03:11 - Introduction
Roger introduces the podcast. The three key opinion leaders, Jörn Schattenberg, Manal Abdelmalek and Naim Alkhouri, discuss their fast-paced, high intensity travel schedules.

00:04:41 - Groundbreaker: a special memory of Stephen
In place of a traditional SurfingMASH groundbreaker, Roger asks each panelist to share a special memory of Stephen. In turn, panelists discuss how they got to know Stephen and/or the role he has played in their lives. Summaries cannot do the emotion of these recollections justice.

00:17:30 - One Harrison accomplishment 
Roger asks the group each to describe an accomplishment that Stephen has left the field. Each panelists provided at least 2 or 3, with no redundancy.

00:23:52 - "Harrisonisms" and wrap-up 
In closing, Roger asks panelists each to provide a favorite "Harrisonism." Answers varied, although every group member recalled Stephen's question, "Is the juice worth the squeeze."

00:33:33 - Question of the Week
Roger asks how listeners feel their lives or work were affected by Stephen Harrison, either directly or indirectly. 

00:33:56 - Business Report 
This week's news on our new newsletter, future conversations, and the Vault, plus more on how we plan to honor Stephen.

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This vault conversation looks back to our coverage of International NASHDay 2023, the predecessor title to this year's Global Fatty Liver Day.

Thursday, June 8 was International #NASHDay 2023 and the podcast hosted a special session featuring patient advocates Gina Villiotti Madison (NASH kNOWledge), Marko Korenjak (European Liver Patients'​ Association) and Michael Betel (Fatty Liver Alliance). With co-hosts Louise Campbell and Roger Green, the group shares both a positive and sobering discussion around the Fatty Liver public health epidemic and its impact on younger generations now and into the imminent future.

Roger starts this conversation by asking Louise to provide more information about the U.K. Parliament debate that had just commenced. Louise notes that MPs from all parts of the UK participated and that they were extremely well-informed on childhood NAFLD and other issues. She notes that members told stories of their own weight loss and government promise to brief MPs on liver disease on an interim basis going forward. One MP said he did not like the term living with obesity, which is considered patient sensitive, because it implies that obesity is a permanent condition. This leads to Roger's closing question which asks each panelist to envision what their organizations' key 2024 International #NASHDay activities might be. While their answer are aligned with what they did for the International #NASHDay 2023, listen for some different twists and new directions.

This is a particularly important and moving episode that captures a range of topics pertinent to the patient perspective and, more broadly, stepping up to NASH.

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This closing conversation introduces two new concepts: the idea that MASH has so many facets that it is comparable to the metaphor of blind people touching an elephant, and the provider mandate to "rule the liver out" when assessing patients with metabolic diseases.  

Roger cites the parable of the blind people touching the elephant as a metaphor for liver disease, which is a precursor for multiple seemingly unrelated diseases (cardiovascular and extra-hepatic cancers, to name two). He says the point is to teach liver disease to healthcare professionals as "the elephant," not its different parts. Louise agrees and suggests that the simple action point for liver disease-as-elephant is to "rule the liver out" when assessing the various related diseases. The test for this must be "cheap" and "accessible;" it does not exist anywhere in the world today.

Roger suggests that the "Keep It Simple, Stupid" approach to liver disease incorporate the two simple action items discussed in this episode. For patients, act now, get screened. For providers, rule the liver out. 

In lieu of a final question, Roger asks panelists to describe one specific initiative they know of that is part of Global Fatty Liver Day. Mike describes a screening activity in Calgary.  He describes a "mistake" last year in letting patients eat healthy food before being scanned. Louise assures him that eating healthy foods will affect scan outcomes less than 1% of the time. Jeff discusses the successes of street teams around the world, who screened 77,000 patients as part of International NASH Day 2023. 
 
 

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Jeff McIntyre uses the discussion between Louise Campbell and Mike Betel as a jumping-off point for discussing some of the larger care challenges and barriers associated with MASH patient care. 

Jeff says the previous conversation between Louise and Michael provides "a really great synopsis" of the challenges and barriers to patient diagnosis and care. He reports that the Global Liver Institute is planning to release its first "Best Practices in LIver Health Policy" report.  For GLI, these challenges are more complex due to the need to find solutions that will work in countries around the world.  He also states that GLI believes the system needs to be intentional not only about diagnosis but also health system follow-through. This requires patient access and country systems set up for success.  Roger raises the issue of having safe spaces for people to exercise in less developed countries. Louise recommends tier systems so that the solution for each country reflects the country's economics. Roger discusses a recent study showing a link between food insufficiency in 4-year-olds and MASLD and MASH later in childhood. Jeff describes the Stockdale paradox: policymakers cannot get caught up in the big picture without dealing with the short-term issues ahead of longer-term success. 

Jeff describes two US health policy cases that reflect the Stockdale paradox:  the VA's initial decision (later reversed) to require biopsy for Rezdiffra and lobbying by the giant food companies to have added sugar included in the list of attributes of healthy food. 

Louise describes "a big to-do" in the UK about children's teeth and access to dentists because poor dental health drives a 7x increase in the risk of liver cancer. She would like to see a generalized dietician who can work with patients on the range of metabolic issues. Mike says it "scares" him about where to start small. Louise gives an example of boiling water before dressing wounds and taking other health actions in Angkor Wat, which led to dramatic declines in diarrhea and the spread of many diseases. 

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This conversation focuses on what happens after or around patient screening, addressing the challenges caused by using GLP-1s and dual incretin agonists to treat concomitant conditions before looking at the patient's liver, and then the opportunities that can come from on-site scanning and immediate feedback. 

Jeff starts this conversation by noting the popularity and widespread discussion around anti-obesity medications, which also have effects on MASH. He says this could "lead to a tricky couple of years" if results include decreased willingness to participate in clinical trials and/or decreased demand for fatty liver drugs from patients already on incretin agonists like semaglutide or tirzepatide. Generally, he expresses a concern that all this will lead to a decline in focus on the liver. 

Louise discusses activities in her two home countries, UK and Australia.  She starts by noting that interest in the healthcare system picks up when patients go to their primary care physicians seeking care for a given disease, in this case, liver disease. She goes on to note that "liver disease is a small portion of poor liver health," which leads to cardiovascular disease and extra-hepatic cancers. Thus, she says screening should identify patients with poor liver health in order to educate and intervene with these non-hepatic conditions. She describes data in her possession that says 33% of Australians who believe they are healthy have poor liver health, and that most of these are post-menopausal women. She says there is a mismatch between patient needs, perceived resource demand, and funds available to support these resources.

Mike asks Louise to comment on scanning as an educational activity. Before answering his question directly, she discusses the value of on-site patient questionnaires in improving the quality and perceived value of the overall visit.   Next, she discusses how she uses the sharing of scan results with the patient to generate a deeper patient understanding of the disease and activate conversation on how patients can help themselves better. Mike agrees based on his experience learning about his high CAP score, then lowering the level. Louise discusses steps treaters can take if the first intervention doesn't work. 

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This conversation centers around the Global Fatty Liver Day 2024 theme and the rationale behind focusing on screening.

It starts with Jeff describing how much has changed in MASLD in the past year and why this calls for a new focus. Jeff identifies the breadth of the global challenge of treating MASLD and related conditions, which is far broader than "just having one medicine for one aspect of the disease in one country." To Jeff and GLI, the best immediate path forward is to bring more patients into the system through screening, which provides the rationale for GLI's theme for the day, "Act Now. Get Screened."

Roger states that this effort will drop a large number of patients "in the top of the funnel," and notes that earlier podcasts demonstrate limited adoption of clinical care pathways or other ways to manage an increased patient volume. He asks Jeff where the care pathway issue fits in the "Act Now. Get Screened" vision. Jeff states this is an issue for the entire field, not just patients, and that the field needs to collaborate on a turnkey way for PCPs to screen easily. 

Roger describes the concern raised Naim Alkhouri (Season 4, Episode 50.3) that the current clinical care pathway approach might create chaos in the system. Also, Roger asks whether US reimbursement policy is far enough along for the various actors to participate. Roger asks about the most effective action that patients and advocates can take. Jeff replies, "Get Screened."

Mike Betel suggests that while this may be an issue for the entire field, he believes the onus for keeping this issue in front of providers must come from patients assertively asking questions and seeking support. Jeff agrees, but describes the relationship between patient and provider in this case as "symbiotic."