Surfing the MASH Tsunami

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The EASL SLD Summit aims at updating a global community of liver stakeholders on the most recent advances in SLD research, both pre-clinically and clinically, focusing on MASLD and tackling the issue of MetALD.

In this episode, Jörn Schattenberg, Louise Campbell and Roger Green review the recently concluded meeting with faculty members Sven Francque and Hannes Hagström in two seperate interviews.

This final conversation from our interview with Sven centers on the research that Sven and his colleagues presented at the SLD Summit.  Most of this research focuses on portal pressures in pre-cirrhotic patients, including those with fibrosis levels as low as F0 or F1. Sven notes that relatively few of these patients have elevations of 10mmHg or more in these earlier stage scenarios, but a significant number have elevations from 5-9 mmHG, which might affect health in more subtle ways. Roger asks about the impact of this work on how we treat patients today and into the future. Sven follows up by identifying several areas for future research. As the groups moves toward the end of the interview, Louise asks questions around using NITs, notably FibroScan, to check for pressures because in some of her work, VCTE in biopsied and non-biopsied livers demonstrated different results. Sven congratulates Louise on the question and indicates this might be a powerful area for future research. 

With that, listen to the full episode to gain a richer understanding than can be described in this summary. If you have questions or comments around the Summit or any other themes addressed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at [email protected].

From the official EASL SLD Summit website:

The EASL SLD Summit aims at updating a global community of liver stakeholders on the most recent advances in SLD research, both pre-clinically and clinically, focusing on MASLD and tackling the issue of MetALD. You will gain insights in the most key techniques employed in research, clinical trials and clinical practice, with an understanding of their potential as well as limitations. You will learn about the most recent advances in our understanding of the disease, including the role of sexual dimorphism, circadian clock or vascular mechanisms, and potential new targets as well as modalities of treatment. You will exchange on these topics with both young fellows and established experts in the field in a highly interactive format with a lot of room for discussion. You will get the latest update on where we stand with the efforts of having MASLD, and SLD in general, on the agenda as a public health problem and the roadmap and policies to tackle this problem, in which the people living with SLD, and many stakeholders have been increasingly joining forces. In light of the latter, the Summit will also provide a space to further discuss the nomenclature change and its potential impact on research clinical practice and awareness. A session will be dedicated to discussing in-depth the issue of people who combine alcohol use and metabolic risk factors, designated as MetALD in the latest nomenclature. You will also get the latest data on diagnosis and prognostication in MASH and on how to tackle MASLD as a multisystem disease, informing you not only on what you need to do, but also on the science and evidence behind it.

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The EASL SLD Summit aims at updating a global community of liver stakeholders on the most recent advances in SLD research, both pre-clinically and clinically, focusing on MASLD and tackling the issue of MetALD.

In this episode, Jörn Schattenberg, Louise Campbell and Roger Green review the recently concluded meeting with faculty members Sven Francque and Hannes Hagström in two seperate interviews.

This conversation starts with Roger asking Sven for his impression about whether the three diseases - MASH, MetALD, Alcoholic SLD - lie on a single continuum or whether the alcoholic and non-alcoholic causes of disease are separate dimensions. Sven suggests that there are different dimensions that can be seen in elements of hepatic structure and vascularization, but that neither are completely independent. Switching to a different challenge around MetALD and alcohol, Jörn discusses the complexity in patients assessing their own drinking behaviors given that much drinking is a weekend-oriented social event rather than a consistent pattern of daily consumption. In the course of this discussion, both Sven and Jörn note their hope that AI/ML will provide pivotal new insights on these issues. Sven comments that he hopes that research will continue to develop along a path of basic science rather than simple drug testing and development. Roger suggests that the relatively low level of efficacy with late stage development drug suggests that we need to learn far more about the basic science to support development of highly successful drugs and NITs.

With that, listen to the full episode to gain a richer understanding than can be described in this summary. If you have questions or comments around the Summit or any other themes addressed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at [email protected].

From the official EASL SLD Summit website:

The EASL SLD Summit aims at updating a global community of liver stakeholders on the most recent advances in SLD research, both pre-clinically and clinically, focusing on MASLD and tackling the issue of MetALD. You will gain insights in the most key techniques employed in research, clinical trials and clinical practice, with an understanding of their potential as well as limitations. You will learn about the most recent advances in our understanding of the disease, including the role of sexual dimorphism, circadian clock or vascular mechanisms, and potential new targets as well as modalities of treatment. You will exchange on these topics with both young fellows and established experts in the field in a highly interactive format with a lot of room for discussion. You will get the latest update on where we stand with the efforts of having MASLD, and SLD in general, on the agenda as a public health problem and the roadmap and policies to tackle this problem, in which the people living with SLD, and many stakeholders have been increasingly joining forces. In light of the latter, the Summit will also provide a space to further discuss the nomenclature change and its potential impact on research clinical practice and awareness. A session will be dedicated to discussing in-depth the issue of people who combine alcohol use and metabolic risk factors, designated as MetALD in the latest nomenclature. You will also get the latest data on diagnosis and prognostication in MASH and on how to tackle MASLD as a multisystem disease, informing you not only on what you need to do, but also on the science and evidence behind it.

Send us Fan Mail

The EASL SLD Summit aims at updating a global community of liver stakeholders on the most recent advances in SLD research, both pre-clinically and clinically, focusing on MASLD and tackling the issue of MetALD.

In this episode, Jörn Schattenberg, Louise Campbell and Roger Green review the recently concluded meeting with faculty members Sven Francque and Hannes Hagström in two seperate interviews. 

The first featured interview is with Sven, who served as one of three organizing members for this year's Summit. In addition, Sven chaired both the opening and closing Plenary sessions on the subject of Metabolism, Alcohol and Toxicity. Sven also delivered a presentation titled Anti-platelet drugs in MASLD: pre-clinical and clinical data. This conversation starts with the co-hosts congratulating Sven on the success of the SLD summit program. In response to several questions, Sven discusses how the organizers began to shape a broader agenda even before the new nomenclature was adopted, and how they broadened further after its acceptance at the EASL Congress earlier in the year. Jörn responds that he felt the expanded focus made the meeting more robust and goes on to highlight the sections he liked best. After Roger asks about anticipated changes in future programs, Sven discusses the tremendous value he saw in having younger researchers present who in turn receive feedback from more senior colleagues. Louise concurs on this point before circling back to discuss the benefits of the MetALD disease classification.

With that, listen to the full episode to gain a richer understanding than can be described in this summary. If you have questions or comments around the Summit or any other themes addressed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at [email protected].

From the official EASL SLD Summit website:

The EASL SLD Summit aims at updating a global community of liver stakeholders on the most recent advances in SLD research, both pre-clinically and clinically, focusing on MASLD and tackling the issue of MetALD. You will gain insights in the most key techniques employed in research, clinical trials and clinical practice, with an understanding of their potential as well as limitations. You will learn about the most recent advances in our understanding of the disease, including the role of sexual dimorphism, circadian clock or vascular mechanisms, and potential new targets as well as modalities of treatment. You will exchange on these topics with both young fellows and established experts in the field in a highly interactive format with a lot of room for discussion. You will get the latest update on where we stand with the efforts of having MASLD, and SLD in general, on the agenda as a public health problem and the roadmap and policies to tackle this problem, in which the people living with SLD, and many stakeholders have been increasingly joining forces. In light of the latter, the Summit will also provide a space to further discuss the nomenclature change and its potential impact on research clinical practice and awareness. A session will be dedicated to discussing in-depth the issue of people who combine alcohol use and metabolic risk factors, designated as MetALD in the latest nomenclature. You will also get the latest data on diagnosis and prognostication in MASH and on how to tackle MASLD as a multisystem disease, informing you not only on what you need to do, but also on the science and evidence behind it.

Send us Fan Mail

The EASL SLD Summit aims at updating a global community of liver stakeholders on the most recent advances in SLD research, both pre-clinically and clinically, focusing on MASLD and tackling the issue of MetALD.

In this episode onSurfing NASH , Jörn Schattenberg, Louise Campbell and Roger Green review this recently concluded meeting with faculty members Sven Francque and Hannes Hagström. Jörn joins both guests as a fellow presenter and the group dives into program highlights with many fascinating takes and interplaying ideas. 

The first featured interview is with Sven, who served as one of three organizing members for this year's Summit. In addition, Sven chaired both the opening and closing Plenary sessions on the subject of Metabolism, Alcohol and Toxicity. Sven also delivered a presentation titled Anti-platelet drugs in MASLD: pre-clinical and clinical data. The following feature with Hannes explores elements of his presentation on how common alcohol overconsumption is in MASLD and how highly this increases risk for future cirrhosis. Throughout both interviews, Jörn is able to elaborate and reflect on his high level of engagement at the Summit as he chaired an industry session and gave three presentations with subjects ranging from clinical trial data (MAESTRO-NASH for resmetirom) to endoscopic bariatric therapies and mitochondrial uncoupling.

With that, listen to the full episode to gain a richer understanding than can be described in this summary. If you have questions or comments around the Summit or any other themes addressed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at [email protected].

From the official EASL SLD Summit website:

The EASL SLD Summit aims at updating a global community of liver stakeholders on the most recent advances in SLD research, both pre-clinically and clinically, focusing on MASLD and tackling the issue of MetALD. You will gain insights in the most key techniques employed in research, clinical trials and clinical practice, with an understanding of their potential as well as limitations. You will learn about the most recent advances in our understanding of the disease, including the role of sexual dimorphism, circadian clock or vascular mechanisms, and potential new targets as well as modalities of treatment. You will exchange on these topics with both young fellows and established experts in the field in a highly interactive format with a lot of room for discussion. You will get the latest update on where we stand with the efforts of having MASLD, and SLD in general, on the agenda as a public health problem and the roadmap and policies to tackle this problem, in which the people living with SLD, and many stakeholders have been increasingly joining forces. In light of the latter, the Summit will also provide a space to further discuss the nomenclature change and its potential impact on research clinical practice and awareness. A session will be dedicated to discussing in-depth the issue of people who combine alcohol use and metabolic risk factors, designated as MetALD in the latest nomenclature. You will also get the latest data on diagnosis and prognostication in MASH and on how to tackle MASLD as a multisystem disease, informing you not only on what you need to do, but also on the science and evidence behind it.

Send us Fan Mail

If you missed this year's Paris NASH meeting, you missed some exciting presentations featuring fresh, pivotal insights about Fatty Liver diseases and some new approaches to learning about this disease. For this episode From the Vault, we take a look back at what has by far been the most downloaded episode in the history of the podcast: S2-E46 - Highlights from Paris NASH 2021. Jörn Schattenberg and Stephen Harrison combine to provide a robust synopsis of the meeting while Roger Green asks a few questions and keeps the discussion in-bounds:

10:20 – Jörn introduces Paris NASH and discusses some of its basics, followed by introduction of Session 1: Epidemiology and the Public Response

14:07 – Stephen discusses potential for integrating home healthcare visits into clinical trials

17:15 – Session 2: Clinical Aspects

17:52 – “NASH does come in different flavors.” Are we thinking about NASH with sufficient granularity?

20:32 – NASH pathogenesis and its link to other metabolic diseases

21:32 – Session 3: Deep dive into fibrosis

24:30 – Talk on “Innovations in imaging assessment in fibrosis” raises pivotal questions about advances we can make in cellular-level understanding

26:57 – Talk from Scott Friedman on “Common mechanisms, molecular evolution and resolution of fibrosis in NASH” yields several key ideas

28:45 – The importance of understanding stellate cell subtypes

33:37 – Jörn and Stephen select some key moments from Day Two

35:45 – Innovations in clinical trial bring researchers to consider competing risks and challenges in determining causes of mortality in NASH trials

40:26 – Session 8, “Global NASH,” describes the size and scale of the NASH challenge around the world

If you have questions or comments around the contents of this episode or the FDA workshop on NITs, drug development or any other themes addressed in this week, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at [email protected].

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In Season 4, Episode 41, the surfers (Jörn Schattenberg, Louise Campbell and Roger Green) review highlights from the FDA's NIT workshop in three seperate interview sessions with guests Naim Alkhouri, Laurent Castera and Veronica Miller. Each guest participated in some form at the meeting and shares slightly differing but incredibly insightful perspectives.

This conversation is the first part of the Surfer’s interview with Veronica. Veronica starts by commending FDA for organizing the workshop and indicates that now we all need to process the data. Roger asks Veronica what FDA might have done better, and she indicates they might have offered more feedback about how far they feel the field has come. She notes that there are many steps ahead and that the FDA needs to be more cautious. She also felt that the mix of data presentations and panel discussions worked well. She points to ballooning and its challenges as the clearest point needing change and then went back to Dr. Johnson’s question about “why are we validating a surrogate with a surrogate?” Roger shares a comment from S1E12 after the first OCA Complete Response Letter and how a regulatory consultant elicited a strong reaction from Stephen Harrison for the same comment. This leads Louise to ask whether we should look to broaden our target outcomes beyond the liver. Veronica notes that we have traditionally looked in an organ-specific way but wonders whether the new nomenclature will focus more attention on metabolic disease, although the topic was not really addressed. As the conversation ends, Roger asks Veronica whether approaches like NAIL-NIT respond to the “surrogate of a surrogate” question. Veronica says that might be right and that other groups like NIMBLE and LITMUS are looking at similar issues, although they sometimes compare to biopsy (which is what drove the surrogate of a surrogate comment in the first place.)

Plenty more ideas are explored as this is both a fascinating and pivotal workshop which covers a range of topics on NITs with presentations by the some of the field's most innovative and knowledgable contributors. If you have questions or comments around the workshop, NITs, drug development or any other themes addressed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at [email protected].

Stay Safe and Surf On!

Send us Fan Mail

In Season 4, Episode 41, the surfers (Jörn Schattenberg, Louise Campbell and Roger Green)  review highlights from the FDA's NIT workshop in three seperate interview sessions with guests Naim Alkhouri, Laurent Castera and Veronica Miller. Each guest participated in some form at the meeting and shares slightly differing but incredibly insightful perspectives.

This conversation begins with discussing a point from a previous episode in 2022 about the difference between NITs to qualify patients for trials versus to evaluate efficacy of drugs. This point stems from the idea that the way disease regresses may not be the same way it progresses. Laurent notes that NIMBLE and LITMUS have demonstrated important results with large data over the last two years. Jörn comments on the limits of using transaminase as a key NIT and Laurent replies by discussing a study over time that shows faster early declines on liver stiffness and slow declines over time as therapy might shift from reducing inflammation to regressing fibrosis. Louise shifts focus to ask about the relationship between kilopascal drops related to lifestyle change, specifically to ask whether these are false positives or real effects. Laurent notes that BMI is a confounder for liver stiffness and that CAP might help assess this issue. Finally, in response to a question from Louise, Laurent answers that we do not know about some of the key changes in test scores, and need to know more.

Plenty more ideas are explored as this is both a fascinating and pivotal workshop which covers a range of topics on NITs with presentations by the some of the field's most innovative and knowledgable contributors. If you have questions or comments around the workshop, NITs, drug development or any other themes addressed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at [email protected].

Stay Safe and Surf On!

Send us Fan Mail

In Season 4, Episode 41, the surfers (Jörn Schattenberg, Louise Campbell and Roger Green)  review highlights from the FDA's NIT workshop in three seperate interview sessions with guests Naim Alkhouri, Laurent Castera and Veronica Miller. Each guest participated in some form at the meeting and shares slightly differing but incredibly insightful perspectives.

This conversation introduces the first part of an interview with Laurent Castera. Roger starts by asking Laurent how he, as one of the few non-American presenters, felt about the meeting. Laurent noted how important the meeting was given that it came from FDA, which the entire world looks to on drug approvals. Jörn notes that his general sense of the meeting is that while researchers have made significant progress with NIT research, particularly around ballooning, FDA might require more data. Laurent concurs, using the pithy statement “inflammation is a driver, liver fibrosis is a killer and steatosis is a marker.” He goes on to discuss the Brunt paper on ballooning before describing that he finds himself concerned that if biopsy is a bottleneck to approval, ballooning is the issue that might limit the number of patients approved for the drug. He sees this as a problem given how confounded the variable is. He closes this comment by noting that while we might have strong biomarkers for fibrosis, we do not seem to have such strength for NASH or drug response. Roger goes on to describe ideas from the past podcast conversation from Season 3 Episode 14 and whether the best next step is to redefine the ballooning variable.  Jörn shares an argument from the workshop that if it is so hard for biopsy to measure the necessary variable, why don’t we simply use the NIT? He also asks Laurent to comment on some unpublished data that Laurent was given permission by Dr. Vincent Wong to share at the meeting. Since the data is unpublished, it will not be described in this summary except to say that it appears extremely important and powerful and, hopefully, will pass review and be published later this year.

Plenty more ideas are explored as this is both a fascinating and pivotal workshop which covers a range of topics on NITs with presentations by the some of the field's most innovative and knowledgable contributors. If you have questions or comments around the workshop, NITs, drug development or any other themes addressed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at [email protected].

Stay Safe and Surf On!

Send us Fan Mail

In Season 4, Episode 41, the surfers (Jörn Schattenberg, Louise Campbell and Roger Green)  review highlights from the FDA's NIT workshop in three seperate interview sessions with guests Naim Alkhouri, Laurent Castera and Veronica Miller. Each guest participated in some form at the meeting and shares slightly differing but incredibly insightful perspectives.

Roger starts this conversation by discussing loss aversion – the idea that an individual’s decision does not reflect an overall fear of risk, but a specific fear of risking something they do not want to lose. Researchers and advocates define loss in terms of time to bring a drug to market or screen fail rates, but for government regulators, “loss” can refer to prestige or credibility when they make what are publicized as “wrong decisions.” Naim registers the issue, but notes that in his clinic, no more than 5% of people test in a way that might qualify them for clinical trials, and probably 1-2% ever participate altogether. He contrasts the high percentage of population with identifiable MASH (which might be 15%) with the 1 in 1,000 “unicorns” in the population that can qualify for trials, suggesting this demonstrates how strongly we need to reconsider testing standards and protocols. Jörn mentions that the FDA commentator in the final session suggested we avoid surrogates altogether and instead look into a million person trial.  Naim agrees that this is not feasible. From here, the group moves to other issues, including cause of death among patients with F0 to F3 fibrosis. As the conversation continues, Louise comments on the idea of doing broader, multi-organ or multi-outcome trials with drugs, as have been done with vitamins. She ends her comment by stating, “I would rather go into the future making the wrong decisions for the right reasons than the right decisions for the wrong reasons.” This statement represents a broader look at how we approve MASH drugs. Naim and Jörn both agree. In the last part of this conversation, Roger asks what Naim anticipates FDA might do next. Naim talks about studies generating more data with more NITs that might lead to what he describes as his “dream” – continuing the biopsy pathway but providing one alternative pathway based on a combination of NITS.

Plenty more ideas are explored as this is both a fascinating and pivotal workshop which covers a range of topics on NITs with presentations by the some of the field's most innovative and knowledgable contributors. If you have questions or comments around the workshop, NITs, drug development or any other themes addressed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at [email protected].

Stay Safe and Surf On!

Send us Fan Mail

In Season 4, Episode 41, the surfers (Jörn Schattenberg, Louise Campbell and Roger Green)  review highlights from the FDA's NIT workshop in three seperate interview sessions with guests Naim Alkhouri, Laurent Castera and Veronica Miller. Each guest participated in some form at the meeting and shares slightly differing but incredibly insightful perspectives.

This conversation covers the first part of our interview with Naim, who served as an expert panelist in Tuesday’s penultimate session. The conversation starts with Naim commending the session and noting that what drug developers and principal investigators truly are seeking is an NIT-based alternative path to conditional approval. Jörn’s response notes that the current alternative – biopsy to measure fibrosis level and NAS activity score – is imperfect, as would be an NIT approach at this time, but notes that he is not certain FDA sees the issue that way. Louise notes and commends Naim for the passion with which he made his case at the meeting. From here, Naim points out that the current system denies care or trial participation to people with clear NASH if the researcher cannot identify ballooning in the initial biopsy. Jörn suggests, and Naim agrees, that NITs need to be selected with an eye toward drug mode of action and markers. He specifically points out the value of MR technology and why he finds it superior to VCTE.

Plenty more ideas are explored as this is both a fascinating and pivotal workshop which covers a range of topics on NITs with presentations by the some of the field's most innovative and knowledgable contributors. If you have questions or comments around the workshop, NITs, drug development or any other themes addressed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at [email protected].

Stay Safe and Surf On!

[Meeting Information from the FDA Website]

Drug development for NASH/MASH with liver fibrosis has increased substantially and there is growing interest in developing NITs to detect the presence of fibrosis, and to accurately classify different stages of fibrosis as well as cirrhosis. Candidate NITs include both blood tests (circulating biomarkers) and imaging tests. In recent years, most data regarding use of NITs have been collected from NASH/MASH clinical trials. However, there are limited published data for use of NITs across the spectrum of the affected population that would be encountered in routine clinical care, including patients without fibrosis. This workshop will assist the FDA in identifying current knowledge gaps for using NITs as diagnostic biomarkers and reasonably likely surrogates, as well as provide a framework for additional data that are needed to fill these knowledge gaps. Ultimately, the FDA seeks to learn whether expert stakeholders have evidence to indicate currently available NITs are adequate to meet the Agency evidentiary standard for assessing primary evidence of clinical efficacy. The primary focus of this workshop is “non-cirrhotic NASH/MASH population with advanced (i.e., Stage 2 or Stage 3) liver fibrosis”. The workshop will not address the use of biomarkers for treatment trials in cirrhosis due to NASH/MASH, however, the workshop will discuss identification of “progression to cirrhosis” using biomarkers.