Surfing the MASH Tsunami

Send us Fan Mail

This final conversation starts by considering prescribing models for other diseases and how they might work here, shifts to discussing the challenges of keeping a patient enrolled in a long-term clinical trial (or even participating in a trial in the first place), and moves on to the final question for the episode. 

The conversation picks up on the FG-21 conversation, particularly how FGF-21 might be prescribed alongside Rezdiffra. Roger Green starts by asking whether and how this prescribing pattern might fit in an "oncology" model, where FGF-21 might be an induction drug and Rezdiffra a maintenance drug. Michael Charlton suggests that benefits from FGF-21s are likely to fade once therapy is discontinued, which would make this model suboptimal.

Jörn Schattenberg raises the issue of keeping patients in the long-term clinical trials necessary to achieve hard outcomes. Jörn advocates keeping his patients in trials but notes that long-term compliance will become increasingly challenging as more therapeutic options become available and the patient may not be improving. Michael suggests we will find similar challenges in recruitment for new trials if patients have to accept the possibility of receiving a placebo. Roger notes that biopsy requirements increase this challenge. 

As the episode winds down, Roger asks participants what they believe are exciting studies likely to come to light over the next three months. Their answers vary. You'll have to listen to learn. 

Send us Fan Mail

This conversation sees the end of the "hot topics" discussion, followed by Michael Charlton discussing issues and excitement around the FGF-21 class.

As we begin, Louise Campbell and Jörn Schattenberg speculate on ways to incorporate metrics like the Dietary Inflammation Index into multifactorial care. Michael asks whether alcohol is figured in the index, given its pro-inflammatory nature, and celebrates the fact that we can now evaluate MetALD patients as a group instead of removing them from classical MASH clinical trials. Louise, who raised the issue in the first place, does not know. As she notes, she first found the issue within the last week. One key question for her is how we can use this in 5-10 years when primary care becomes a key player in MASLD and all metabolic diseases. 

Roger Green's hot topic involves "Ask the MD" columns in US newspapers and magazines. He gives "two cheers" for help columns in which MDs recommend that MASH patients  "go to your doctor and ask for an ultrasound."  He asks whether the PCP is the right destination and whether "ultrasound is the test to seek. However, he appreciates that all this brings MASH badly-needed visibility in the public eye. Michael and Louise agree that given how few patients are treated today, any such public acknowledgment is positive.

Michael discusses the emerging excitement around the FGF-21 class. The recent agents from Akero and 89bio are "emerging as highly potent" in terms of PDFF change and transaminase responses. While we need to learn more, he asks how this will fit in with Rezdiffra and, more generally, how long we can give a patient a "potent" growth factor and what will happen if/when the patient needs to discontinue therapy. Jörn and Michael note adherence challenges with this therapy; Roger comments that even with daily oral drugs, adherence can be a challenge.

Send us Fan Mail

After Michael Charlton finishes discussing research he finds compelling, Jörn Schattenberg and Louise Campbell each describe one item they have been focusing on recently. 

Michael mentions the recent JAMA publication of a small, randomized controlled trial exploring the use of low-dose aspirin in biopsy-confirmed MASLD patients, which he describes as "a tremendous result." The results suggest benefits in terms of both fat fraction (PDFF) and transaminase levels. Jörn provides more detail about the trial. While the sample size was small, the results were highly promising. There is much to learn here from a larger RCT and also from understanding the biological mechanism better, but the group agrees this is a promising development.

Roger Green asks his fellow Surfers to discuss one item that has attracted their attention in the past week. Jörn Schattenberg goes first and discusses the upcoming Innovations in SLD Think Tank 2024. He expresses excitement that changes in format should yield unique, high-value benefits. Roger notes that Jörn and his co-chair Jeff Lazarus will discuss the think tank's results during the episode posting on May 15. 

Louise mentions her constant pursuit of finding ways to improve prediction with FibroScan.  In doing so, she found a study indicating correlation between the Dietary Inflammation index score and kilopascal level on FibroScan testing. Investigators are exploring the use of this index in an array of non-liver diseases related to metabolic syndrome or chronic kidney disease, but the correlation with kilopascals is fairly clear. Louise would like to see research looking at controlled attenuation parameter, since she can usually "see a fat change faster than a stiffness change." 

Send us Fan Mail

Michael Charlton and the Surfers discuss two issues: defining therapeutic futility for Rezdiffra and describing some advances in MASLD translational medicine. 

The conversation starts by continuing the topic of therapeutic futility. Louise Campbell asks Michael how he plans to determine therapeutic futility with Rezdiffra in terms of side effects or efficacy. Michael indicates that he will continue patients on Rezdiffra as long as their disease does not progress. While he would prefer a more robust approach, he describes the scale of challenge in defining futility for a drug where FibroScan and transaminase levels did not provide strong prediction.

Roger Green asks what percentage of patients are taking concomitant GLP-1 therapy. This leads to a brief sideline discussion on levels of therapeutic adherence.

Roger asks Michael what he find exciting in translational medicine these days. Michael cites the LiverRisk score, a developing test he describes as "substantially superior" to other biomarkers. His group is currently working with NHANES data to see whether this is predictive for patients who had transient elastography and met MASH criteria. He particularly wants to determine whether this is a dynamic test. 

Michael goes on to discuss the work his group is doing on the microbiome, where he and others are finding potentially valuable insights. The challenge continues to be how to translate these insights into clinically meaningful interventions.

Send us Fan Mail

In this initial conversation, Michael Charlton describes some ways that the presence of Rezdiffra has affected practices and procedures in his clinic and shares issues he and his colleagues are discussing. 

As the conversation begins, Michael hails Rezdiffra as proof that as a species, "we can be capable of amazing things in a good way," a drug approved by FDA to reverse fibrosis in a significant number of patients with the world's most common liver disease. From there, he goes on to discuss the challenges his metabolic live disease clinic faces in prescribing the drug. The first issue: the label provides "tremendous latitude" in defining the target F2/F3 patient properly.

Jörn Schattenberg asks about the patients coming to his clinic and how much knowledge they possess of the disease and medication. He also asks how Michael discusses Rezdiffra with them. 

Michael describes a clinic with hepatology and endocrinology, nutrition support and a group of nurses all of whom can do elastography.  Some patients want medication, others seek to care for themselves first through nutrition and physical activity plans. In all cases, the clinic takes a holistic approach, particularly because most patients have at least one more metabolic complication.

Michael shifts to a second issue: futility. The label does not include information on treatment-stopping criteria.  He alludes briefly to a leading KOL group that is creating "something to help the field" decide which patients to treat and when to stop therapy, among other issues. 

Jörn asks whether the clinic is setting up a new panel of test for these patients, Michael states that the clinic relies mostly on standard tests: FIB-4, ELF, FibroScan, and, for patients above a certain threshold, MRI. 

Send us Fan Mail

Michael Charlton joins Jörn Schattenberg, Louise Campbell, and Roger Green for a far-reaching conversation that covers ways Rezdiffra is already impacting MASH patient treatment, exciting recent studies and broader issues in clinical trial recruitment.  

00:00:00 - Surf's Up: Season 5 Episode 11
Opening comments from the panel, including brief quotes taken directly from the episode. 

00:02:32 - Introduction
Opening comments (re)introducing listeners to Michael Charlton

00:04:34 - Groundbreakers
Each panelist shares one piece of good news from the previous week.

00:06:56 - Impact of Rezdiffra launch on Michael's clinic 
Michael hails Rezdiffra as "an amazing thing" in terms of its global impact. He goes on to discuss the challenges his clinic faces in properly defining the target F2/F3 patient. 

00:14:40 - Defining positive response and treatment futility 
In response to a question from Louise, Michael indicates that he will continue patients on Rezdiffra as long as they do not progress. 

00:19:44 - LiverRISK score
The conversation shifts to focus on progress in translational medicine. The first item Michael cites is LiverRIsk, which he terms "substantially superior" to other biomarkers. Next, he mentions his group's work on the microbiome and the challenges in translating items like these into clinically meaningful interventions.

00:23:15 - Low-dose aspirin as anti-MASH medicine 
Michael discusses the recent JAMA publication of a small RCT suggesting benefits from use of low-dose aspirin in biopsy-confirmed MASLD patients.  He and Jörn agree that while the sample size was small, the "highly promising" results might be worthy of discussion with patients.

00:26:29 - Jörn and Louise share their items of interest
Jörn discusses his excitement about the upcoming Innovations in SLD Think-Tank 2024 and its new format. Louise discusses a study indicating correlation between the Dietary Inflammation index score and kilopascal levels. 

00:33:27 – Questions about the Dietary Inflammation Index 
Louise and Jörn speculate on ways to incorporate this kind of result into multifactorial care. Michael asks whether alcohol figured in the index given that many MASH patients consume alcohol. 

00:35:38 - Roger on patient feedback
Roger asks how panelists feel about MD columnists recommending that MASH patients  "go to your doctor and ask for an ultrasound."  Michael and Louise agree that given how few patients are treated today, any such public acknowledgment is positive.

00:38:11 - Excitement and questions surrounding FGF-21s
Michael discusses the emerging excitement around the FGF-21 class. "emerging as highly potent" and asks questions its use and long-term value to patients. The group discusses adherence challenges with a q1w injectable therapy. 

00:41:26 Therapeutic models for MASH prescribing 
Roger asks whether prescribing for FGF-21s might align with an "oncology" model, with FGF-21 as induction drug and Rezdiffra as maintenance drug. Michael suggests that benefits from FGF-21s are likely to fade once therapy is discontinued. 

00:43:08 - Challenges in clinical trial recruitment and adherence
Jörn, Michael and Roger all agree on the growing challenge of keeping patients in the long-term clinical trials necessary to achieve hard outcomes.

00:47:24 - Closing question
Roger asks participants what they believe are exciting studies likely to come to light over the next three months. 

00:49:33 - Question of the Week
The question asks how much value old standard drugs like aspirin or pioglitazone are likely to bring to MASH or MASLD patient treatment.

00:50:22 - Business Report
This week's news on audience metrics, SurfingMASH sponsorship, spring events and this week's Vault conversation.

Send us Fan Mail

This episode is a follow-up to Season 4, Episode 5, where we met Tim Jobson. His company, Predictive Health Intelligence (PHI), takes a unique approach to identifying and monitoring MASLD patients using basic EHR data and analytics. This session explores PHI's work over the past years and considers implications for several liver-related health challenges. 

00:00:00 - Surf's Up: Season 5 Episode 10
Opening comments from the panel, including brief quotes taken directly from the episode. 

00:02:04 - Introduction and Groundbreaker
Each panelist shares one piece of good news from the previous week.

00:07:02 - New projects from Tim
Tim discusses the three major activities that PHI has undertaken since our last visit.

00:12:46 - Sequential testing
Roger Green asks Tim to state one key lesson he would like to share with a global audience. Tim speaks of the value of sequential testing and the value of collecting data that will support this effort. 

00:15:33 - Data governance and privacy
Louise Campbell asks Tim about privacy issues and GDPR status for these types of basic health information. Tim states that the number of cases where patients have exhibited concerns when they learn the data is helping them get/stay healthier is virtually nil.

00:22:31 - Most and least helpful data items
Tim states that "factual data" (e.g., lab tests) are more valuable than "coded data" reflecting a treater's point of view. 

00:25:21 - Thoughts on patient gender and age 
In response to Louise's questions, Tim shares that his group creates separate analyses by gender, strongly prefers creating risk thresholds to "measures of normality and abnormality," and already is seeing a trend of patients needing MASLD care at younger ages. 

00:30:23 - Differences between MASLD and HCV
Tim discusses some differences in the challenge of bringing in-need HCV patients into the healthcare system compared to in-need MASH patients. HCV patients tend to live at lower socio-economic status, and some who lead high-risk lives may be homeless. MASH patients are more likely simply to lack knowledge and more likely to come to a physician visit once identified. 

00:38:38 - Specific challenges in the US
In response to Roger's questions, Tim identifies two differences in the US today: greater clinician motivation due to Rezdiffra coming to market and a greater need for an inexpensive way to target the right patients and then track whether the drug appears to be working.

00:41:49 - Keeping data import simple
Tim comments that these kinds of activities are challenging enough when data sets and needs are fit to goal and fairly simple, let alone if researchers or policymakers inflate the dataset unnecessarily. This is particularly important because the system can probably locate so many untreated patients using simple data. 

00:47:18 - Seeking high-value patients more effectively and final question
Louise and Tim consider what might be the "sweet spot" when patients are ill enough to appreciate that they need treatment but still hardy enough that therapy has time to work. From there, Roger asks a final question about how all stakeholders can contribute to the goal of aggregating large-scale basic sequential data.

00:52:52 - Question of the Week
The question asks what help listeners' organizations or others like them can offer in providing data or otherwise helping enrich data sources for assessing the value of repeat measures. 

00:53:37 - Business Report
This week's news on audience metrics, post-Rezdiffra episode ideas and this week's Vault conversation.

Send us Fan Mail

This conversation comes from our coverage of The EASL Congress, 2023, when Sven Francque and Ian Rowe joined Jörn Schattenberg and Roger Green to consider primary care screening at the top of the Clinical Care Pathway. The original conversation had a robust write-up: 

Ian starts this conversation by pointing to unmet needs in the primary care setting for disease identification. He refers to a related presentation of interest from Vincent Wong titled A clinical care pathway to detect advanced liver disease in patients with type 2 diabetes through automated fibrosis score calculation and electronic reminder messages: a randomized controlled trial. Ian suggests that this study proves both the value of working to identify more patients and the considerable amount of work remaining in this area. The group goes on to discuss what the implications of this study are for treatment in primary care both now and into the future of patient care. In particular, Jörn elucidates the value of FIB-4 not only as a screening tool for liver-related outcomes, but also as a predictor of cardiovascular risk and all-cause mortality. Secondly, Jörn notes that when a NASH therapy becomes available, "the granularity of picking up those patients will be higher" and physicians will be more motivated to take action provided that they have both a screening tool and available treatment to prescribe. This leads to discussion around the differences between hepatology and private medicine practices and management of a population-level disease. Ian raises the question around how frequent should testing be performed in the primary care setting for different pathways. 

Send us Fan Mail

This conversation focuses on how the need for biomarkers will evolve in an era of in-office screening and MASH drugs and ends with answers to Roger Green's closing question. 

Hannes Hagstrom starts this conversation by noting that one challenge as MASH drugs become available involves knowing when to discontinue or add to therapy since, as he points out, Rezdiffra will not be efficacious for all patients. This leads Jörn Schattenberg to the need for predictive biomarkers that will be specific to drugs or modes of action. These have not been studied much to date. Jörn is confident these will not be today’s biomarkers, but is unclear about whether they should point to genotype, mode of action or something else. After some byplay about how quickly this can come about (years vs. decades), Roger Green suggests that one key to commercial success will be the identification of this exact type of biomarker.

Louise Campbell broadens the group's focus somewhat by noting that since changes in nutrition and physical activity will be part of any regimen we need to assess the impact of these as compared to the drug itself. Jörn describes this vision as “kind of scary” but notes that diet and exercise labeling is standard for drugs in the US, exactly as it is with Rezdiffra, and these are not monitored closely. From there, we consider the kind of study one might do to assess nutrition and physical activity independently and why that might be extremely hard.

From there, the discussion moves on to Roger's final question, in which he asks what steps each panelist believes will take place in the next two years to support improved triaging and patient management through the system. Four active minds produce more than four answers. Listen to learn.

Send us Fan Mail

This conversation explores the implications of increased access to economically viable in-office screening, particularly when primary care practices begin to use the new scanning devices.

Roger Green begins this conversation by recalling a concern Naim Alkhouri expressed during S4 E50.3, that primary care reliance on FIB-4 can flood the pathways with many “wrong” patients, which might lead to confusion within the channels. Hannes Hagstrom describes a role for primary care at the top of the funnel if practitioners have clear guidance and training. Roger suggests this approach will make primary care providers triagists. The group agrees as long as primary care has clearer guidance based on a limited set of reliable, widely used tests and algorithms. In this context, Jörn Schattenberg suggests that while VCTE might be the first point-of-care test, perhaps EHR-based algorithms can be created and deployed to identify the optimal number and types of patients to bring into the system.

This reliance on algorithms can create another challenge. Hannes notes that many algorithms are being published but none are becoming the standards that will be key to primary care assuming a triage role. Louise Campbell feels that the fact that VCTE is fundamentally non-discriminatory between modes of action makes it a good tool as part of this, but we have lots of screening and education before bringing protocols or devices into a primary care setting. As the conversation wraps up, Hannes notes that we will need to keep some patients out of the pathway due to age or low level of disease to identify two qualifiers and that when we have multiple drugs and different lines of therapy or treatment patterns, that will recast the issue once again. algorithms are being published but none are becoming standards, and standards will be key to the primary care as triage approach. Louise Campbell feels that the fact that VCTE is fundamentally non-discriminatory between modes of action makes it a good tool as part of this, but that we have lots of screening and education to do before bringing protocols or devices into a primary care setting. As the conversation wraps up, Hannes notes that we will need to keep some patients out of the pathway due to age or low level of disease to identify two qualifiers and that when we have multiple drugs and different lines of therapy or treatment patterns, that will recast the issue once again.