Surfing the NASH Tsunami

This conversation comes from our first look at MASEF, last September, when lead author Mazen Noureddin joined the Surfers to discuss his recent breakthrough paper on this new NIT.  The original conversation had a robust write-up:

Mazen Noureddin joins co-hosts Jörn Schattenberg, Louise Campbell and Roger Green to discuss serum identification of at-risk MASH and the Metabolomics-Advanced Steatohepatitis Fibrosis Score (MASEF). In late July, Mazen co-authored a paper on the subject which was published in Hepatology.

This conversation begins with Louise’s initial response around the setting of application for MASEF. She poses a question that leads the group to explore possible pros and cons of different approaches and the potential impact each might have in terms of cost effectiveness. For example, Jörn wonders how feasible it will be for non-experts to administer. Mazen suggests that its application will be relatively easy before explaining how to navigate the caveat of a gray zone similar to that of VCTE. After a few more comments on sequential pairing with FIB-4, Mazen next teases the possibility of demonstrating therapeutic efficacy in the drug development space. 

Louise returns to a question around cohorts and asks whether variables like age or sex has an impact on the test’s capabilities. She then asks whether this sort of work has the potential to inform retrospective cardiac studies. After Mazen and Louise go back and forth with a few ideas in response, Roger makes the comment that he is struck by the wide breadth of application and describes the platform as “elegant.” As the conversation winds down, the group discusses a few comparisons between different blood-based markers. 

If you have questions or comments around MASEF, metabolomics or any other ideas considered in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at questions@SurfingNASH.com. The Surfing the NASH Tsunami will be back next week with more original content.

After some final discussion about GLP-1s, this conversation entails Roger Green summarizing what he has heard in the episode so far and testing for confirmation or correction. It goes fast and covers significant ground. 

Naim Alkhouri starts this conversation by discussing patients for whom he would prescribe resmetirom vs. GLP-1s. Lean MASH patients are likely to receive resmetirom. Earlier fibrosis patients are more likely to receive semaglutide. A multimorbid F3 patient might receive both. 

Roger asks how things might change with tirzepatide, since it is a dual agonist with strong MASH-lowering effects. Naim expresses doubt that tirzepatide will be antifibrotic, since neither GLP-1 nor GIP have direct liver effects. He has more faith in the glucagon dual- and triple-incretin agonists. 

The rest of the conversation involves Roger stating themes he has heard earlier and asking for confirmation or amendment. It moves pretty fast, covers a lot of territory, and receives some agreement and some correction.

This conversation touches on two important subjects: the impact of different potential resmetirom prices on the size and structure of the treatable MASH population, and the impact GLP-1s are having (and will have) on clinical trial recruitment and basic patient treatment. 

It starts with Naim Alkhouri expressing concern over the $39-52K price he has heard for resmetirom, which ICER has deemed cost-effective. He mentions another paper that says a price of $19,000 would be cost-effective. To Naim, this magnifies a question that is already quite widely considered: when to prescribe resmetirom vs. a GLP-1 agent. He discusses some patient factors that might go into his decision. 

Naim describes ways that GLP-1 use, which can be sporadic or episodic, is affecting clinical trial recruitment. Ian Rowe discusses the current use of GLP-1s in the UK and suggests that if the price for resmetirom is high enough, GLP-1s will receive significant use. 

Naim Alkhouri shifts direction slightly, from discussing current GLP-1s to exciting recent clinical trial report. He focuses on two: survodutide from Boehringer Ingelheim and efruxifermin from Akero Therapeutics. Recent exciting results from BI and Akero suggest to Naim and others that the future for drugs is bright. 

Ian Rowe anticipates a significant amount of co-prescription of GLP-1s and resmetirom in this population. GLP-1s have already demonstrated clear cardiovascular, weight loss, and HbA1c-lowering benefits. To Ian, that creates sufficient motivation to prescribe GLP-1s to multimorbid patients with diabetes, obesity and most likely MASLD or MASH. To him, the price of resmetirom will have a tremendous impact on how often UK physicians rely on GLP-1s alone.

This conversation focuses more tightly on the specific challenges with the current approaches that use NITs to diagnose and stage advanced MASH fibrosis and explores several newer options and ways of thinking about the challenge.

Roger Green notes that recent papers discuss the failure to predict accurately with FIB-4. He asks how we can improve predictive performance. Louise Campbell notes some specific challenges, after which Jörn Schattenberg praises John Dillon's work in automating lab detection algorithms. He also reiterates his view that repeat testing will be pivotal in good test protocols. Ian Rowe rejoins the conversation (from a faulty Internet connection) to comment that our inability to stage patients reliably will lead to government payers like NHS believing that they will need biopsy to stage patients accurately and treat them cost-effectively. Jörn says Germany will work differently and if EMA approves it, it will launch in Germany.

Roger asks about new tests on the horizon and specifically whether there is sufficient improvement in diagnosis, staging or treatment. He refers specifically to MASEF and Naim Alkhouri's earlier comments about four scan vendors at his conference. Ian says there are tests that can rise to this task, but they are not produced in sufficient quantity and cost too much to become a first-line option. Naim notes that the most exciting tests are a couple of years away. Ian returns to Jörn's earlier point about the value of sequential testing vs an individual test. Louise suggests that device size will be pivotal for primary care.

This conversation explores the challenges with using the current non-invasive tests (NITs) to diagnose patients with F2/F3 advanced MASH fibrosis. If tests today cannot achieve the requisite level of precision, panelists explore other ways to define patient targets.

Roger Green starts by recalling that in a recent episode (Season 5 Episode 2), Jeff McIntyre suggested that in the US, the initial patient population may be as small as a few hundred thousand people. Ian Rowe states that current tools are incapable of placing these patients in a narrow diagnostic or therapeutic window. Jörn Schattenberg takes a "pragmatic" approach to defining the patient he is certain to treat; test results are a small part of his calculus.

Naim Alkhouri shifts the discussion to focus on VCTE cutoff points for cirrhosis. The interplay between Naim and Ian suggests that different practices and guidelines carry with them different cutoffs. Jörn expresses gratitude that the can watch the US and learn from that experience. He notes the tension between wanting a cost-effective system and large numbers of patients clamoring for the new medicine. The need to rule some patients out is obvious, the way to do so is challenging.

Asking, "What can we do besides scan" or use conventional tests, Naim discusses some newer options, starting with the metabolomics-based MASEF score discussed in Season 4 Episode 39. He also mentions the LiverFast test. Jörn describes factors that can render a test inappropriate for a particular patient. Louise suggests the right test will depend on the specific question the provider is trying to answer.

This conversation explores why proper use of non-invasive tests (NITs) will play a pivotal role in increasing the number of patients diagnosed and treated for MASH. It becomes particularly pivotal if, as expected, the first MASH drug is approved later this month.

Roger Green starts this conversation by describing why he considers NIT use and adoption one of the two pivotal patient treatment issues for 2024. Jörn Schattenberg notes that he has not received any referrals from PCPs or endocrinology based on elevated FIB-4, which would happen if enough front-line treaters were adopting the new clinical care pathways. Educational efforts have begun, but do not seem to be changing behavior yet. As Jörn puts it, "We're still preaching, and I haven't seen it in much activity."

Naim Alkhouri states that his experience is the same as Jörn's. He reminds us that we covered some of these issues in a 2023 end-of-year conversation (S4 E50.3). He reiterates his concern with FIB-4 as a standalone first-line test and states his preference for combining it with an in-office scan. He comments that at the recent Desert Liver Conference, four companies displayed these devices, each with a different price point and convenience factor. 

Ian Rowe describes the British experience as being different: "every patient with elevated ALT in the context of metabolic risk factors has a FIB-4 and now has a FibroScan." His biggest concern is that tests are insufficiently precise. If we have top-end and bottom-end cutoffs, he fears, "you're going to end up excluding a lot of patients who would be potentially eligible for treatment."

In 2024, the two major areas for change in diagnosing and treating MASH  are new drug approval and changes in use of NITs. Naim Alkhouri and Ian Rowe join Jörn Schattenberg, Louise Campbell and Roger Green to consider what might change with NITs and how having an approved drug might change thinking on this issue.

00:00:00 - Surf's Up: Season 5 Episode 5
Opening introduction, including brief quotes taken directly from the episode discussion.

00:02:36 - Introduction and Groundbreaker
Panelists congratulate Naim on the recent, highly successful Desert Liver Conference. In the groundbreaker, each panelist shares one piece of good news from the previous week.

00:06:36 - Why Focus on NITs?
Roger describes why he considers this issue worthy of an episode. Naim and Jörn both state that they have received no referrals from PCPs or endocrinology based on elevated FIB-4 tests. Ian notes that the UK has guidelines and pathways built into some protocols; these make it challenging to stage a patient as F2 vs F3 vs early compensated cirrhosis.

00:13:06 - NITs and treating F2/3 MASH patients 
Ian says that current tools are incapable of defining the small nitial target patient population Jeff McIntyre suggested in Season 5 Episode 2.  patients clearly enough to place them in a narrow diagnostic or therapeutic window. Jörn takes a "pragmatic" approach to defining the patient he is certain to treat; test results are a small part of his calculus. Naim shifts the target patient to focus on VCTE cutoff points for cirrhosis. There is no clear cutoff.

00:18:45 - Tests worth using beyond the widely discussed options
Asking "What can we do besides scan" or use conventional tests, Naim discusses some the new blood-based tests. Jörn describes factors that can render a test inappropriate for a particular patient. Louise suggests the right test will depend on the specific question the provider is trying to answer.

00:22:59 - Improving on FIB-4
Roger notes that recent papers discuss failure to predict accurately with FIB-4. In the conversation that follows, panelists agree that automating test results and using a series of tests instead of a single event will both have real value.

00:28:27 - New Devices and Blood-Based Tests for Use in Office
Roger asks about new tests on the horizon and specifically whether there is sufficient improvement in diagnosis or treatment. Naim notes that the most exciting tests are a couple of years away. Ian returns to Jörn's earlier point about the value of sequential testing vs an individual test. Louise suggests that device size will be pivotal for primary care.

00:35:30 - Impact of Resmetirom Price
Naim expresses concern over the $39-52K price he has heard for resmetirom. Roger states that price reflects size of target market. At that point, the discussion veers toward factors that drive drug prices higher.

00:40:22 - Impact of GLP-1s on treatment and resmetirom
Roger asks the group what the impact of consumer-driven GLP-1 use is likely to be on US prescribing of MASH drugs. Ian discusses use of GLP-1s in the UK and suggests that if the price for resmetirom is high enough, GLP-1s will receive significant use. Recent exciting results from BI and Akero suggest to Naim and others that the future for drugs is bright.

00:47:16 - Final question
This entails Roger summarizing what he has heard in the conversation and testing for confirmation or correction. It goes fast and covers significant ground.

00:53:26 - Question(s). of the Week
The question is what else will change, besides prescribing, once a drug is improved and what the industry can to do optimize change.

00:54:06 - Business Report
News on audience metrics, the upcoming Question of the Week, future episodes and this week's Vault co

Two years ago, Surfing the MASH Tsunami conducted two episodes with Chris Estes, then the chief modeler for the Center for Disease Analysis Foundation exploring issues around CDAF's then-recent publication of a NASH/MASH disease model. This conversation centers on issues of advanced fibrosis. We thought it might be interesting to look back at that episode in lieu of today's topic. Here are the summary notes from 2022:

This conversation starts with Chris Estes describing the processes he and his colleagues at the Center for Disease Analysis Foundation have used to build a disease model for NAFLD and NASH prevalence in 15 countries. Chris discusses some of the unique challenges that modeling NASH presents. Among other items, these include (a) spontaneous regression of disease; (b) "excess" mortality (mortality not from liver disease where NASH is a contributing factor); and (c) interplay of demographics (gender, age, race, etc.) and co-morbidities (most notably Type 2 diabetes) with disease.

When Chris ends his initial comments, Jörn Schattenberg asks about the viability of using obesity as the anchor for increasing prevalence estimates instead of diabetes, noting the varying definitions of BMI across countries. Chris notes that obesity is imperfect but adds that we have robust, stable, long-term obesity data bases in most countries, whereas diabetes estimates are newer and many people with diabetes to not recognize they have the disease.

The last element in this conversation starts with Alina Allen noting that for clinical trial development, researchers test patients with a range of diagnostics. As a result, they do not need to develop estimates based on (or even linked directly to) obesity or diabetes. Alina asks what models can tell us that can help bring down high placebo rates in double-blinded, placebo-controlled clinical trials. Chris mentions meta analyses as recently as seven years ago that exhibited negative disease progression over time and adds that any assessment of F3 (or even F2) fibrosis is affected by concomitant disease.

This conversation is sponsored by Resoundant, a Mayo Clinic company and the developers of Magnetic Resonance Elastography. MRE is widely available with over 2000 locations worldwide, and can be done as a low-cost, rapid exam in just 5 minutes. Together with PDFF, this quantitative exam is called an Hepatogram – a powerful non-invasive alternative to liver biopsy in many cases. For more information, visit www.resoundant.com on the web.

As the episode comes to an end, the group winds up focusing on the need for better, more frequent MASH education as a pivotal need if we are to flatten the growth curve of the MASLD pandemic. In the process, the discussion returns to the risk for women and the important role they can play. 

Louise Campbell starts this conversation by harkening back to the issue of post-menopausal women. As she notes, women provide most of the hands-on care in health system, and also do most of the cooking and food shopping for the home. To Louise, targeting women also targets children, so educating women will have multiple derivative benefits.

Zobair Youonossi agrees completely, particularly for the low SDI countries. I suggest that slowing prevalence and disease has two elements: fewer patients at the starting line (or with early MASLD) and better therapies and programs for patients who already live with the disease. I also ask whether the consumer uptake of GLP-1s might have an impact in the US.

Zobair states that educating children is the key long-term driver and that the effect of consumer medical behaviors like taking GLP-1s is likely to be minimal. He also believes that MASLD requires more attention from global and national governmental and non-governmental players…NOW!

This episode does not have a formal closing question, but the rest of this conversation offers a wrap-up of each panelist’s perspective.

This conversation focuses largely on the work of the Global NASH Council, an effort of over 200 stakeholders in more than 50 countries to address a range of macro issues in the MASLD space.

Zobair Younossi, who is the Global NASH Council Chair, starts this conversation by discussing a specific Global NASH Council project on how to implement guidelines for different specialties across regions. He offers two reasons this is such an important project.

1. In general, Zobair notes, 90% of the content in guidelines is virtually identical, but the other 10% might vary widely. The goal of the Global NASH Council is to identify this last 10%, understand the reasons for these differences, and seek to align them better.
2. As he points out, guidelines are worthless without effective implementation. The second goal of this project is exactly that: to improve implementation.

Zobair goes on to discuss other Global NASH Council projects, ranging from shared biopsies to the previously mentioned modeling activities. He notes its growth in size and expresses gratitude to the other global MASLD leaders, including Jörn Schattenberg, who are part of one of more of the Council's major projects.

Roger Green asks Zobair to put the guidelines project and the Council's policy focus in the context of his earlier comments about high SDI vs. low SDI countries. He describes differences in what food insecurity means between the two types of nations and how that should affect each country’s pursuit of policy and guidelines. He also suggests that it will be more important to provide patient and provider information for specific low SDI countries.

In this opening conversation on MASLD disease burden, Zobair Younossi summarizes and expands on some key points from the recent Diabetes Spectrum review article he co-authored with Linda Henry.

Zobair starts by discussing the recent review article, Understanding the Burden of Non-Alcoholic Fatty Liver Disease: Time for Action which he describes as "a summary of a large body of evidence that's being generated." He points to three pivotal issues:

1. The treatment burden associated with MASLD and MASH is extremely high and will grow over time. The prevalence of MASLD in the overall population has grown to ~38%, but for Type 2 diabetics, who have worse outcomes associated with MASLD, this number is 68%. MASH numbers are estimated to be 5-7% in the general population, but 37% among T2D patients. As diabetes increases across the globe, these rates will go higher.
2. The humanistic burden, as measured in Quality of Life scores, is also significant. Patients living with MASLD and MASH report lower QoL scores, which translates not only into a less happy, more depressed society, but also into significant indirect economic effects due to poorer worker performance and, presumably, more time away from work. 
3. The economic burden of MASLD is significant in every country, but the scale and structure of this burden varies from country to country. Key drivers include dietary issues and inactivity, and issues are becoming more pronounced globally. These economic issues are driven largely by the key downstream sequelae. The leading causes of death from MASLD are cardiovascular disease and extrahepatic cancers, which are costly, and patients with cirrhosis are highly susceptible to liver cancer as well. 

Jörn Schattenberg joins the conversation to commend Zobair on his work, which, as Jörn puts it,  "educate[s] us as physicians on where the risk factors and the at-risk populations are, and we're moving that way. I mean, we're trying to focus on patients with diabetes that are more advanced from the hepatologist perspective." He also discusses the ongoing effort to educate endocrinologists and primary care about these issues as well, since those two specialties treat the lion's share of diabetic patients. 

Zobair goes on to describe the Markov models of disease cost his group has built already in seven countries, and plans to build in more. Key point: MASLD is costly everywhere, but the structure of cost and, most importantly, public health solutions will vary from country to country.

Initially, this conversation focuses on how cost-effectiveness issues relate to the MASLD Disease Burden. In the process, Zobair Younossi provides education on some of the metrics and concepts pivotal to drug value assessment.

Roger Green starts off asking how the economics of treating MASH stack up against hypercholesterolemia at the birth of statins in the 1980s, where the medical benefit was clear but economic was harder to manage. Zobair proceeds to describe the process by which the cost effectiveness of drugs is measured, computation of Quality Adjusted Life Years, or QALYs, and how different countries vary in the level of QALYs they consider cost effective. He also notes that within the US, at least, we may be willing to accept five times greater cost per QALY than for another. He also points out that cost effectiveness grows as new therapeutic options include price competition into a market.

Louise Campbell shares the specific US cost numbers from Zobair’s article, which she describes as “frightening,” particularly given the rate of growth in the disease and society’s lack of efficacy in shifting the curve on this. Zobair responds by saying that one goal of the article was to create awareness that regular surveillance of diabetic patients for MASLD could have a significant economic impact in the US. 

As the conversation winds down, Jörn Schattenberg comments that all this is a team effort and Zobair agrees heartily.

This conversation starts with a focus on slowing the growth of the MASLD pandemic, and then veers slightly into a discussion of the specific issues post-menopausal women face with MASLD. 

Roger Green starts by commenting how it seems both pivotally important and highly efficient to find a way to flatten the growth curve, and he asks Zobair what he considers key to doing so.  Zobair replies that the key is to focus on multidisciplinary care centered around primary care, which will require extensive physician education. He also comments that countries may differ widely in what their current MASLD priorities should be. He introduces the idea of the sociodemographic index and the difference between high and low SDI countries. To Zobair, it is critical to elevate the issue of how to support low SDI vs. high SDI countries, which involves, in different ways, every stakeholder from WHO down to patients and their advocates.  

Louise Campbell shifts focus to point out that the article raises a point about the increased risk of MASLD to postmenopausal women. This brings up a range of comments, the most important of which revolve around the need to educate OB/GYN physicians and their allied providers on the important liver risk to post-menopausal women.

Zobair Younossi, Chair of the Global NASL Council, publishes seminal papers  on MASLD epidemology, cost of disease, and related public health needs regularly. Co-hosts Jörn Schattenberg, Louise Campbell, and Roger Green ask questions and share perspectives from their own experiences.

00:00:00 - Surf's Up: Season 5 Episode 4
Opening introduction, including brief quotes taken directly from the episode discussion.

00:02:45 - Introduction and Groundbreaker
Panelists swap brief, lighthearted comments about where they are geographically and where they have been recently. In the groundbreaker, each shares one piece of good news from the previous week.

00:11:15 - Epidemiology article
Zobair Younossi discusses the recent review article, Understanding the Burden of Nonalcoholic Fatty Liver Disease, published earlier this month in Diabetes Spectrum. He starts by discussing incidence and growth rates for MASLD, MASH, and cirrhosis across the world, and how these differ by country. He goes on to discuss the impact of MASH on patient Quality of Life and the high correlation between multi-metabolic patients (most notably diabetics) and negative outcomes.

00:15:55 - Panel questions and comments
Jörn Schattenberg joins the conversation to praise this and other of Zobair's works for helping physicians know what to do when they decide to become more engaged in treating MASLD and MASH. This leads Zobair to discuss the Markov model they have created to evaluate burden of disease.

00:19:14 - Costliness and cost-effectiveness of therapy
In response to a question from Roger Green, Zobair describes the criteria and metrics used to evaluate the cost-effectiveness of a new drug or diagnostic. Louise Campbell comments on how high and underappreciated the social and economic burdens of disease are to every global society. Zobair notes that health economists do not focus on liver disease as a discreet set of costs and burdens.

00:27:17 - Goals and activities for the next few years
Roger states that given how fast the  MASLD and MASH populations are growing, an effort to "flatten the curve" would be heroic. Zobair replies that each country needs to fight liver disease, but that each country will have different immediate challenges.

00:31:28 - Women's health and liver health
Louise notes that the epidemiology paper refers to the high level of risks among women over 55. This leads to a discussion between Jörn, Zobair and Louise on the higher risk level post-menopausal women experience and some pathological elements that make this important.

00:34:58 - Global NASH Council
Zobair bridges this portion of the conversation to discuss the work of the Global NASH Council, a group of >200 members in >50 countries organized into different workstreams to create knowledge and awareness around MASLD and MASH.

00:38:59 - Low SDI and High SDI countries
To Zobair, one element in the global effort on MASLD and MASH is the recognition that High SDI (wealthier) and Low SDI (power) countries face dramatic differences in the challenges they face.

00:41:14 - Reducing the rate of disease growth
To Louise, educating women might be a key to driving awareness, both because post-menopausal women live at higher risks and because they cook and schedule for their families. This leads to a broader discussion about the most effective education starting with children. Finally, Zobair discusses the importance of making all stakeholders PLUS global agencies recognize the scale of this challenge and to act in concert with increasing urgency.

00:48:42 - Question of the Week
The first Question of the Week asks what steps each of us can take to help stem the pandemic.

00:49:41 - Business report
News on audience metrics, the first Question of the Week, next week's episode and this week's Vault conversation

Our first conversation focusing on the new MASLD nomenclature surfaces as part of our coverage of the EASL Congress 2023. Hepatology researchers and key opinion leaders Sven Francque and Ian Rowe joined Jörn Schattenberg and Roger Green to discuss the value of the new nomenclature and its current and anticipated impact on their practices. 
This conversation focuses on the outcome of the nomenclature process, a three-stage Delphi process that produced new names and classifications for what had previously been known as fatty liver disease and henceforth will be known as steatotic liver disease (SLD). Sven, who was actively involved in the entire exercise, gives a concise summary of the process by which the new classifications were developed and how the new terminology will work. The rest of the conversation focuses on three issues.

1. Excitement that we will now have the opportunity to study patients whose disease has both metabolic and alcohol-based components.
2. The processes by which the three clinicians, Sven, Ian and Jörn are starting to share the new structure with their patients with varying degrees of success. One interesting observation emerges here from Sven: the English language terms do not translate equally into Dutch, so there is a patient advocate-led effort to create a new set of terms in Dutch.
3. Roger raises concerns about implementation planning for the new nomenclature. One concern is around the possible impact on drug or diagnostic development and the other is about the kinds of communication issues covered in earlier episodes. Sven, who again worked more closely on the process, states with confidence that the change will not have an impact on drug or diagnostic trials. Subsequent events prove Sven right.

This conversation ties up several issues related to MASH and the new MASLD nomenclature that the panel did not touch on earlier in the episode. These range from the impact the nomenclature might have on other elements of treatment to the impact of this effort over time. Finally, the panelists grade the process to date (they admit, their views might be a bit biased) and signs of success. 

Roger Green starts this conversation by asking what impact panelists believe the new MASLD nomenclature might have on NITs. From one perspective, Meena Bansal notes that it should have no impact given that NAFLD/NASH and MASLD/MASH map so similarly on top of one another. From a different perspective, Jeff Lazarus asks whether the nomenclature and accompanying guidelines from professional societies will result in more testing. The group aligns around the idea that patients living with Type 2 diabetes are an excellent target for increased testing with NITs given the high overlap of the two groups. Maru Rinella comments specifically that all efforts to tie T2DM to MASLD as frequently common metabolic diseases will be helpful and that discussing the proper use of NITs might be one way to make this connection. Louise Campbell agrees that increased focus on "Healthy Livers, Healthy Lives" will drive exactly these kinds of discussions. The rest of the episode consists of Roger asking panelists three questions, to which they respond: 

1. What might change over the next year or two? Meena believese that approval of a drug will drive significant growth in the learning curve and, with that, enhanced disease awareness and understanding. Jeff suggests that this will not take the form of a transition from NAFLD to MASLD, but instead that people first learning about the disease will use the new nomenclature properly. Mike Betel notes that on the Fatty Liver Alliance website, ~98% of searches are simply for "fatty liver disease." Over time, he anticipates this will change and also that websites like FLA will address "fatty liver" queries in terms of new nomenclature. 
2. Impact on ICD codes. Meena, who is doing significant work in this area, answers that the goal is to have no impact but simply a smooth cutover. 
3. How the group would grade its work on this activity to date. As Jeff notes, answers from the people who led the process are likely to be quite biased, but all gave fairly high grades. 

This conversation focuses on how the new MASLD nomenclature might improve providers' explanations of MASH to patients. Louise Campbell describes new opportunities, while Meena Bansal describes how focusing on metabolism provides a richer opportunity for providers to explain to MASH patients why fat on the liver matters.

Louise Campbell starts this conversation by discussing a new NHS program providing primary care centers with VCTE units they can use to screen patients for MASLD and MASH. She points out that this will provide a unique opportunity to present the new MASLD nomenclature to primary care and allied health providers in a way that connects immediately to diagnosing patients and educating them properly about their disease. She notes that at the patient level, the discussion is still likely to focus on excess fat on the liver but presents the idea of "fat" in a less stigmatizing way.

Meena Bansal focuses more specifically on exactly how provider-patient conversations might change. For years, she suggests, physicians have written "hepatic steatosis" on patient charts, but then told patients they "just have a little fat on the liver." In her view, the new nomenclature will take the word "just" out of the discussion and present the "little fat on the liver" as part of a metabolic syndrome that requires treatment. She goes on to mention another source of excitement: the ability to consider MetALD patients as part of the same MASLD community and add them to Mt. Sinai's longitudinal patient registry, which will likely become a rich source of MetALD data.
Earlier in the episode, Jeff Lazarus had mentioned his excitement at the growing role and publicity for the "Healthy Livers, Healthy Lives" initiative. Louise notes that increasing focus on liver awareness and awareness of the importance of liver health, as discussed in Season 5 Episode 2, aligns neatly with Meena's disease description and the new communication opportunities for new physician and allied health specialties.

This conversation shifts from the rearview to the path ahead. Louise Campbell starts by asking about the role of Allied Health Providers in the process. After this issue, process leaders Maru Rinella, Jeff Lazarus and Meena Bansal discuss how this will roll out as we move ahead.

It starts with Louise Campbell asking why there Allied Health Providers did not play a larger role in the Delphi process. Maru Rinella replies that, in her vision, this group’s involvement will be critical in the rollout and message development but less so in a Delphi process that was mostly about hashing out, as Maru puts it, “the nuances of the disease.” To Maru, this is also the place where patient voice brings the most pivotal value. Meena Bansal notes that there were some PAs and NPs in the Delphi process. Meena Bansal agrees that their role will be critical in discussions on how to communicate the disease to the patient (a topic we return to in later conversations). Louise appreciates, accepts and largely agrees with this discussion. 

Roger Green shifts focus from the past process to ask about the rollout phase: when it began, what it will include and when it might end. Meena says it will never end. Jeff Lazarus comments that while publication was the formal rollout, even before then groups were vying to be the first to change their names. He also noted that the article was published simultaneously in several journals with broad, rapid uptake in the literature. Since the key is to raise awareness and educate the population, he considers the speed and breadth of uptake a major sign of success. Maru Rinella comments that journal participation has been generally excellent.

This conversation focuses on the Delphi process for a new MASLD nomenclature. It starts with Jeff Lazarus describing what a Delphi process is and how it worked here. Jeff and two other key players in this process, Maru Rinella and Meena Bansal, describe what they consider some of its greatest strengths as well as one thing they wish had worked out better.

Jeff's description focuses on the four rounds of data gathering and some key activities that transpired before the formal process began. He goes on to identify what he considers some of the pivotal outputs of this one. In particular, Jeff describes the focus on patients with alcohol and diet issues, and the naming of a new discreet disease for these patients (MetALD) as being “revolutionary.” 

Roger Green agrees with Jeff's assessment that the naming of MetALD was an important outcome and that the process had clear benefits in this way. He goes on to ask why people opted out of the process. Maru Rinella comments that some people opted out after the third phase due to disagreements with the direction of the activity. Roger refines the question to ask why people opted out in the first place. Jeff and Maru note the amount of work required for this kind of activity, and he, Maru Rinella and Meena Bansal all describe that not all invitees understood how important this process would be upon first invitation. Jeff and Maru go on to mention that the participation rate was high, somewhere around 80%.

Roger asks what could have gone better. Maru, Jeff and Meena Bansal each note groups for which they wish participation had been broader, including possibly a broader representation of stakeholders (notably, more patients, although Maru notes this was not for lack of trying) and more organizations or countries.

This conversation focuses on the issues and visions that led to the identified need for a new MASLD nomenclature. Maru Rinella and Jeff Lazarus discuss the original goals of the process and how focus broadened and shifted throughout.

It starts with Maru Rinella describing what she terms “an existential crisis” for the field around a publication suggesting changing the name of the disease from “non-alcoholic” fatty liver disease to “metabolic” fatty liver disease. She considers this the main impetus for key global players to converge. Jeff Lazarus notes that stigma and several other processes came into the discussion. Maru and Jeff agree that the participant recruitment process came in two phases, one where it was hard to get participants and a later point where it was to manage the size of the exercise. Jeff felt the tipping point happened when people understood how the Delphi process would work and also the need for this to succeed. Maru felt that people had to grasp the implications of a consensus process, which Delphi is. As the conversation ends, another leader in the process, Meena Bansal and a patient advocate participant, Mike Betel of the Fatty Liver Alliance, describe how they came to enroll.