Surfing the MASH Tsunami

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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.

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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.

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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

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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.

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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. 

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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.

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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.

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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.

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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.

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The process of creating a new MASLD nomenclature for the condition formerly known as Fatty Liver Disease was a multi-year process with unique challenges and complications. Three leaders in the process, Maru Rinella, Jeff Lazarus and Meena Bansal, and patient advocate Mike Betel join Louise Campbell and Roger Green to discuss the process, transition and rollout.

00:00:00 - Surf's Up: Season 5 Episode 3
Co-hosts Louise Campbell and Roger Green sit with Maru Rinella, who co-chaired the New Nomenclature process, Jeff Lazarus, who oversaw the entire Delphi process, Meena Bansal, who played a key role and co-moderated the 2023 AASLD session, and patient advocate Mike Betel to discuss the entire process from inception to today and beyond.

00:03:57 - Meet Meena Bansal
Dr. Meena Bansal, Division Chief at Mt. Sinai Hospital in New York, discusses how she became involved in liver disease and her current research interests, and shares one fact about herself that might surprise you.

00:05:47 - Groundbreaker
Panelists share one piece of good personal or professional news from the previous week.

00:08:22 - Characterizing the Nomenclature Process
Maru and Jeff discuss the original goals of the process and how focus broadened and shifted throughout.

00:16:02 - How the Delphi Process Worked
Jeff describes the overall process. Roger asks about people who chose not to participate at the outset, which leads to a discussion about the overall rate of participation. Roger then asks what might have worked better, which leads Maru, Meena and Jeff to discuss groups they wish had been better represented.

00:27:05 - The Role of Allied Health Providers
Louise asks why Allied Health Providers did not play a larger role throughout the process. Maru and Meena differentiate between providers' roles in the early process and the mechanics of rolling out to the patient community.

00:29:38 - Focusing on the Rollout
Roger's question about the rollout leads Jeff to focus on some of the key early stage events. Jeff and Maru go on to discuss the high level of participation from key journals.

00:33:32 - Early Awareness
Mike Betel brings a piece of data on physician awareness from the pre-test of a study he is conducting in Canada, which serves as a conduit into the entire topic of who is aware of the nomenclature today and how knowledge will spread over time.

00:38:56 - The New Message for Patients
Louise notes that the upcoming UK effort to bring VCTE screening to primary care will provide an effort to define and characterize the disease for patients. Meena comments that providers have done this informally for years, but while the message used to be that the patient "just has fat on the liver," this nomenclature will formalize the disease, remove "just," and focus the patient on therapy.

00:39:15 - MetALD - A New Disease in the SLD Family
Roger states that in his mind, the newly defined disease MetALD is a major positive outcome of the process. Maru, Meena and Louise each describe ways this new definition will aid diagnosis and treatment, Mike notes that the message still must be tailored for each patient.

00:43:55 - Implication for Diagnostics
The group discusses the idea that while the nomenclature will not lead to new diagnostic tests, it might lead to increased and more appropriate use of the tests that exist.

00:48:25 - The Future of the Nomenclature
Roger asks the group where this process will be in a year and five years. Answers vary.

00:51:58 - Grading the Process So Far
Roger asks panelists how they grade the process to date. Grades are high although, as Jeff notes, they are grading their own work.

00:55:27 - Business Report
News on audience metrics, the upcoming Question of the Week, next week's epidemiology discussion and this week's Vault conversation