drugtrial

Drs. Michael Charlton and Mazen Noureddin and Global Liver Institute Director of Global NASH Programs Jeff McIntyre join Dr. Stephen Harrison, Louise Campbell and Roger Green to review some of the most important and exciting presentations from the final two days of the 2021 TLMdX, the annual meeting of AASLD.

 Each panelist chose 1-2 presentations or posters from the 2021 TLMdX from AASLD that they thought conveyed a major topic or question in the meeting. The group discussed each paper, sometimes moving far afield the original topic. As usual with SurfingNASH, conversations were interspersed with challenging insights and comments, debate and laugher.More additional info about this episode?

Highlights include:
3:31 - Introducing tonight's panelists
17:51 - Michael Charlton and Mazen Noureddin kick off reconsideration of "Efficacy and Safety of Pegbelfermin in Patient with NASH and Stage 3 Fibrosis: Results from the Phase 2b FALCON 1 study" (Late Breaker 1.) Group discussion ensues throughout this section
35:21 - Mazen discusses "PROXYMO Demonstrates Safety and Efficacy of Cotadutide, a novel Incretin Co-Agonist in Biopsy-Proven Non-Cirrhotic NASH with Fibrosis" (Late-Breaker 1)
43:09 - Group discussion
48:36 - Stephen Harrison discusses "Vonafexor, a FXR Agonist, Induced Hepatic and Renal Improvement in the Randomized, Double-Blind, Placebo-Controlled LIVIFY NASH Trial" (Late-Breaker 1)
55:36 - Group discussion
1:03:12 - Louise Campbell discusses "Impact of Modest Weight Reduction on Serum Markers, Liver Histology and Disease Progression in Patients with Advanced Fibrosis Due To Nonalcoholic Steatohepatitis (NASH)" (Parallel 29)
1:09:12 - Group Discussion
1:15:13 - Louise Summarizes "The Fibrosis-4 Index and Severe Liver Disease Outcomes in Primary Care: a Stratified Cox Analysis" (Parallel 29)
1:20:29 - Group discussion
1:21:59 - Michael discusses "ARO-HSD, an Investigational RNAi Therapeutic, Demonstrates Reduction in ALT and Hepatic HSD17B13 mRNA and Protein in Patients With NASH or Suspected NASH" (LP11)
1:26:23 - Group Discussion
1:28:16 - Jeff McIntyre discusses "Lifestyle Management of NAFLD with Obesity" (Emerging Trends Symposium, "Tailoring NASH Therapy"
1:39:11 - Group discussion
1:46:08 - Final question: "What's the one thing that you hope that the part of the community that you touch most directly is going to take out of this meeting?"

Profs. Scott Friedman and Michelle Long, Dr. Naim Alkhouri and Global Liver Institute DIrector of Global NASH Programs Jeff McIntyre join Louise Campbell and Roger Green to review some of the most important and exciting presentations from the first three days of the 2021 TLMdX, the annual meeting from AASLD.

Description: Each panelist chose 1-2 presentations or posters from the 2021 TLMdX from AASLD that they thought conveyed a major topic or question in the meeting.  The group discussed each paper, sometimes moving far afield the original topic. As usual with SurfingNASH, conversations were interspersed with challenging insights and comments, debate and laugher.

Highlights include:
5:27 - Introducing tonight's panelists
15:27 - Naim Alkhouri discusses "The Prevalence of Alcoholic and Nonalcoholic Fatty Liver Disease in Adolescents and Young Adults in the US" (Parallel 5)
20:33 - Group discussion
28:56 - Louise Campbell discusses "An advanced practice provider (APP) pathway achieves more effective weight loss in NAFLD patients compared to standards of care" (Parallel 2)
37:40 - Group discussion
46:28 - Scott Friedman discusses "The influence of host genetics on liver microbiome composition in patients with NAFLD" (Poster #`1654)
48:39 - Scott transitions to "The influence of host genetics on liver microbiome composition in patients with NAFLD" (Poster #1781)
50:31 - Scott ties these two results together in addressing the importance and complexity of microbiome: "I say that ...in part based on the work of Marty Blazer...an infectious disease doctor, who's sort of convinced me that epidemiologically it's very hard to explain how a disease showed up on our radar screens in a 20 to 30 year period, uh, that didn't exist before...Certainly our genes haven't changed over hundreds, if not thousands of years, to any extent. And so something external has changed. It comes back to the environment," and dietary changes.
52:53 - Group discussion
58:48 - Michelle Long discusses "Longitudinal association between MRE and liver-related events and CV events in NAFLD" (Sunday Presidential Plenary session)
1:07:56 - Group discussion
1:09:08 - Group discussion shifts toward the question of whether and when FDA might move away from biopsy as the requisite endpoint in drug trials
1:15:03 - Roger shares audience question on probiotics and NAFLD. Scott provides primary answer
1:16:37 - Jeff discusses Donna Cryer's talk on "Grit, Grace, Gratitutde and Resilience: What You Wish Your Doctors Knew about You" (Sunday Patient Forum)
1:22:53 - Group discussion starts by considering the best word to describe the optimal provider:patient interaction ("partnership" emerges as preferred choice)
1:28:23 - Roger discusses "Topline Results from the Alpine 2/3 Study," a Phase 2b trial evaluating 3 doses of the FGF19 Analogue Aldafermin,(Sunday Presidential Plenary session) and "Efficacy and Safety of Pegbelfermin in Patient with NASH and Stage 3 Fibrosis: Results from the Phase 2b FALCON 1 study." He connects these results by saying "What was striking is that if all you were doing was scoring the balls and strikes, then you'd say that those were both the same thing because neither one of them was going to point to a commercial success in launch." However, he continues, "the differences between the two vastly outweigh the similarities" in that pegbelfermin demonstrated minimal ability to differentiate from placebo while aldafermin clearly differentiated from placebo but might not have presented a strong enough commercial profile given other drugs in development.
1:33:07 - Group discussion
1:36:25 - Scott adds one comment on the importance of digital pathology if we are to continue relying on biopsy.
1:37:04 - Final question: "What's the one thing that you hope that the part of the community that you touch most directly is going to take out of this meeting?"

Jörn Schattenberg and Mazen Noureddin join the Surfers to discuss five recently-reported or ongoing clinical trials in NASH cirrhosis. The reviews focus on study findings and their implications, but also on the methods used to conduct each trial and the implications of these designs on generalized learning and ability to move beyond the biopsy.

Stephen Harrison leads the group in discussing recent results from NASH cirrhosis trials, including the REVERSE trial with obeticholic acid, the FALCON 2 trial with pegbelfermin and a post-hoc analysis of Galectin Therapeutics' Phase 2 trial for belapectin. The group also discussed ongoing trials including the FGF-21 efruxifermin, the FGF-19 aldafermin, the Galectin-3 inhibitor belapectin and the combination agent trial from Gilead Sciences. Along the way, Terns Pharma CEO Sen Sundaram joins from the audience to ask whether the name "cirrhosis" is the most appropriate way to define the disease, given all that we are learning. This session takes a deep look at cirrhosis, with focus on clinical trials, disease pathology and patient management.

Manal Abdelmalek, Ken Cusi and Jörn Schattenberg join Louise Campbell and Roger Green to discuss key presentations at AASLD 2021 and preview SurfingNASH's coverage of the event. This virtual meeting runs from November 12-15 and is scheduled on East Coast time.

Highlights include:
9:19 – Roger begins the conversation, by describing the AASLD program elements and what SurfingNASH will cover.
10:46 – Manal Abdelmalek kicks us off by focusing on Dr. Neil Henderson’s Hans Popper (Basic State of Science) Lecture and the relevance his talk will have meaning for NAFLD and NASH.
12:53 – Ken Cusi links this talk to Monday’s Emerging Trends Symposium on “Tailoring NASH Therapy.”
15:26 – Manal identifies Friday’s Liver Cell Biology SIG, with its focus on gut-liver access and gut microbiota triggering, as another source of knowledge and insight for future potential NASH therapies
16:45 – Jörn Schattenberg raises Parallel Session 10 on Diagnostics and Biomarkers of NAFLD (Sunday, 10:00a) which will focus on LITMUS work in which he participated. He goes on to describe the research and how it can drive better patient treatment in advance of medications.
19:05 – Louise discusses the Public Health and Healthcare Delivery SIG (Friday, 5:30p). She is excited that the session will discuss the foundational role a behavioral approach health can play, particularly in the absence of medications. 
19:58 – Roger, Louise, Jörn and Manal mention Friday afternoon sessions of particular interest. 
22:51 – Louise identifies “a couple of really good sessions on Saturday,” the Women’s Health Program (4:00p) and Parallel Session 2 on “Health Services and Public Health” (10:00a)
23:20 – Ken Cusi summarizes some high points of the post-graduate course. 
25:34 – Manal kicks off our conversation of Sunday presentations by discussing two talks from the plenary sessions: the presentation of the Alpine 2/3 results by Stephen Harrison and the longitudinal association between MRE and liver-related and cardiovascular events in NAFLD.  Jörn adds a though by noting the inclusion of CVD results and then discussing their meaning.
28:03 – Manal notes the presentation from the Million Veteran program, 
28:33 – Roger discusses some speculation from the podcast around the time of the aldafermin withdrawal and expresses the hope we will learn whether aldafermin was more a clinical or commercial failure. Jörn questions whether the decision to read out biopsies at 24 weeks may have been part of the reason the trial missed its primary endpoint
29:42 – Louise points out Parallel Session 17 titled “NAFLD and NASH: Predicting Outcomes and Response to Interventions” (Sunday, 4:00p) and its possible connection to some recent podcast topics
30:08 – Manal refers to the diagnosis and biomarker session Sunday as an opportunity to delve deeper into machine learning and artificial intelligence, after which Roger and Manal discuss the insights that AI  improves and those it does not. 
32:14 – Ken raises the joint AASLD-ALEH symposium Sunday (1:00p) as an excellent opportunity to learn more about the challenges stakeholders face in Latin and South Ameria and the southwestern US.
33:29 – Jörn notes that the panel has not discussed the sessions covering clinical trials of novel therapies and identifies some trials of interest.
36:14 – Manal mentions a paper at Parallel Session #33, Experimental Advances in NAFLD (Monday, 3:00p) that looks at single-cell RNA sequencing in mice to identify that hedgehog signaling in hepatocytes is a critical early event for NAFLD fibrosis in humans.
37:25 – Ken expresses optimism about the quality of the meeting, departs. 
39:01 – Louise, Jörn and Roger identify other sessions of interest on Monday.
42:23 – Final question focuses on what panelists anticipate will be the most powerful takeaway from the meeting. 
46:33 – Business Section 

 Alina Allen and Ian Rowe lead the Surfers in considering biopathological shortcomings in fibrosis as a solitary endpoint. Their comments stem from Alina's presentation of the recent Mayo Clinic paper, "MRE for Prediction of Long-Term Progression and Outcome in Chronic Liver Disease: A Retrospective Study." In this conversation, Alina summarizes the paper, after which Stephen Harrison asks questions about availability of subgroup analysis.

This conversation focuses on flaws in biopsy as a measurement device and also in fibrosis as a solitary endpoint.

In the rest of the discussion, the group discusses challenges in proving that NITs can accurate measure and differentiate between different drugs in terms of therapeutic efficacy. One challenge is with the current metrics. We speak frequently about the challenges with biopsy and with fibrosis being an ordinal variable, but as Alina notes, being too tied for fibrosis means we focus solely on one measure of improvement and downplay others, such as steatosis.

The conversation is too rich and nuanced to be captured in a paragraph or two. This episode is worth two or three listens to capture all its points.

Alina Allen and Stephen Harrison spearhead a discussion on how MRE results can provide a foundation for developing Subpart H Clinical Trial Endpoints from non-invasive testing data. Their comments stem from Alina's presentation of the recent Mayo Clinic paper, "MRE for Prediction of Long-Term Progression and Outcome in Chronic Liver Disease: A Retrospective Study." In this conversation, Alina summarizes the paper, after which Stephen Harrison asks questions about availability of subgroup analysis.

 For NASH to move "beyond the biopsy," researchers must develop reliable clinical trial endpoints using non-invasive tests. This conversation winds up centering around MRE's ability to provide those metrics.

It starts with two different points. Ian Rowe comments on the power of message in dealing with patients. Specifically, he notes that the word "cirrhosis" does not engender strongly emotional or motivated responses whereas the word "cancer" certainly does so. Next, Stephen Harrison asks how cleanly we can translate MRE results into transient elastography readings. Ian suggests the answer is "not very clearnly."

Then the meat of the conversation starts, as Stephen asks whether MRE and LSM can lead us to a viable Subpart H surrogate endpoint. For this to work, he notes, we would have to translate LSM and/or liver function readings into a metric that then translates into an outcome. Alina Allen notes that MRE has the benefit of producing consistently read results without the reader variability issues we find with biopsy. Stephen pushes further, noting that it would be a major step to link magnitude of effect to a one-level fibrosis change, Alina reveals that the number falls consistently around 19%. Alina notes that we have no similar relationship for MELD scores, but the group agrees in the end it should be possible to design trials around MRE-based outputs.

Professors Alina Allen and Ian Rowe join the Surfers to discuss our ability to predict long-term outcomes using MR Elastography. The conversation flows around Mayo Clinic's recent Hepatology publication, "MRE for prediction of long term progression and outcome in chronic liver disease.
 
The ability to predict long-term outcomes using MR Elastography (MRE) and other non-invasive testing methods will be pivotal to drug development and, separately, to diagnosing, staging and monitoring patients. Alina presents highlights from Mayo's recent CGH paper and lends her own significant experience in this area. As we learned last year, Ian leads or is involved in large population-based studies in Leeds, with considerable focus on how NITs can support patient treatment most successfully and cost effectively. This is a topic where all five panelists can contribute from unique perspectives reflecting their own experiences.

Highlights include:
8:53 - Alina Allen begins to discuss recent Mayo Clinic publication "MRE for Prediction of Long-Term Progression and Outcome in Chronic Liver Disease."
10:22 - Source of data for this retrospective analysis
11:33 - Discussion of results starts by discussing accuracy in pre-cirrhotic patients
13:05 - Key point: biomarkers can tell us more because they are continuous numbers, not two or three level models
14:08 - Stephen Harrison asks for specific numbers that listeners can use as rules of thumb for prediction
15:08 - Alina -- a 1 point increase in kPa...more than doubles the risk of cirrhosis for pre-cirrhotic patients, increases risk of decompensation by 22% in compensated cirrhotics
18:53 - Ian Rowe describes results as "great because it speaks to the development of more personal risk stratification for patients."
19:53 - Alina expands on the benefit for clinicians who need to treat and manage individual patients more intelligently and cost effectively
22:08 - Ian describes a study he and his team in Leeds are conducting that addresses similar issues. 
24:09 - Alina raises question of how to monitor sub-F2 patients in hepatology and even primary care clinics
24:59 - Louise Campbell: same metrics will allow us to individualize terminal care and palliation sooner for patients whose livers will fail. Leads to a more in-depth discussion with Ian on what should happen in the UK today vs. what is happening. 
27:39 - Alina describes palliative care in the US as "an area that needs a lot more work" and raises some of the challenges
30:13 - Stephen asks whether we can reverse engineer or analyze these results for FibroScan. Ian reports that his data suggests this is a more complicated challenge. 
31:41 - Stephen asks about implications for endpoint designation in pre-approval outcomes studies, then suggests an alternate design with endpoints based on MRE
33:10 - Alina agrees with idea, referring to Scott Friedman's point in S2 E51 about the genesis of NAFLD activity scores and fibrosis levels
34:45 - Alina: "I think this connection between what we currently use to what we need to move in the future is starting to get made" and paints a picture for what trials might look like.
36:15 - Stephen asks whether we know enough to propose a Subpart H endpoint that is not biopsy driven. He and Alina agree we are close to having one key endpoint proven: a 20% decreasae in MRE correlates to a 1 level decrease in fibrosis.

Antaros Medical's Chief Scientific Officer Lars Johansson joins Stephen Harrison, Louise Campbell, and Roger Green to reprise the key points of his recent Paris NASH talk. In this section, panel members speculate on the largest, most important conceptual changes that the new imaging approaches can drive in disease knowledge and research.

This session begins with Lars discussing the value of 3-D MRI, a technique he discussed in Paris, as well as work he did not mention in Paris that looks at spleen volume. The conversation ends with each panelist answering two questions from Roger. First, he asks the panelists to "Dare to Dream" the one most significant advance each one hopes will ensue from these imaging advances. After this, he asks two final wrap-up questions. To Lars, he asks the most important messages listeners should take from this episode. To the others, he asks the most "mind-blowing" thing they heard.

Antaros Medical's Chief Scientific Officer Lars Johansson joins Stephen Harrison, Louise Campbell, and Roger Green to reprise the key points of his recent Paris NASH talk. This conversation revolves around the implications of Lars's comment that we should track and analyze functioning hepatocyte cells as an excellent marker for liver function.

This conversation starts with a comment from Louise Campbell that this entire approach might play a significant role in moving us beyond the biopsy. Lars agrees, noting that studying fibrosis and fat reduction places too much emphasis on "what shouldn't be" in the liver instead of focusing on "what should be," which are high functioning hepatocytes. To explore hepatocyte function, he discusses use of gadolinium contrast agents, more than 50% of which are taken up by hepatocytes. This provides a setting to combine dynamic functional inputs based on hepatocyte function with static measures based on stiffness and PDFF. This provides a truly dynamic look at liver disease, which is particularly important given the liver's ability to regenerate. Stephen spends the last few minutes of the conversation by discussing the results this approach can yield and contrasting it favorably to the techniques we use today, some of which are difficult to implement and none of which provide the richness of information achievable with the imaging techniques Lars describes.

Antaros Medical's Chief Scientific Officer Lars Johansson joins Stephen Harrison, Louise Campbell, and Roger Green to reprise the key points of his recent Paris NASH talk. In this conversation, Lars and Stephen discuss the value of assessing the balance of fibrogenesis and fibrosis in healthy and unhealthy livers.

Introducing our guest surfer, Stephen Harrison describes Lars Johansson's Paris NASH talk as "remarkable and intriguing." Lars begins his comments by discussing the use of PET tracers to target fibrosis through Collagen Type I cells as well as hepatic stellate cell activation through PDGFR beta. He and Stephen go on to discuss two critical ways the resulting insights can change drug development: first by identifying the correct circulating blood biomarkers to include in different trials or pieces of research, and second by optimizing combination therapies based on the specific effects each agent has on the fibrosis and fibrogenesis processes. On the latter issue, Stephen suggests this approach might have benefit not only in NASH but also a broader range of metabolic diseases Lars concurs.

Mazen Noureddin joins Stephen Harrison, Louise Campbell and Roger Green to close our series of "Biggest Stories of NASH Summer." In this conversation, Louise Campbell raises two very different points about the earlier conversation.

Louise's first point has to do with steps taken to maintain compliance with clinical trials and whether researchers can analyze these in a way that will help front-line treaters understand what are keys to patient pharmaco-adherence. This leads to a conversation about why trials are managed the way they are and what it is reasonable to expect from front-line practices. Louise's second point asks us all to envision the biopsy the patient provides as a "gift" and to consider how we might treat samples differently if we viewed them that way. The conversation circles back to Stephen's multiple sample slide idea, with Stephen and Mazen discussing what the impact of this approach might be in terms of screen fail rate and placebo response. Finally, Stephen makes predictions for the Ole Miss - Alabama football game, which will have occurred by the time you listen.

Ian Rowe, Michelle Long and Manal Abdelmalek reveal what they consider the most important NAFLD/NASH stories of summer.

Which NAFLD/NASH stories did they choose? The newly-appointed Professor Rowe discusses the importance of the FDA approval of the ELF test as a prognostic for cirrhosis. True to her epidemiological background, Professor Long reviews the prospective prevalence study that Stephen Harrison, Naim Alkhouri and others conducted in San Antonio. Finally, Professor Abdelmalek uses a comment she received at a presentation this summer as a jumping-off point to discuss potential value currently available generic drugs -- metformin, statins, carvedilol -- in treating portal pressure among cirrhosis patients. Some highlights:

4:39 - Ian Rowe's understated announcement
6:31 - Ian's event: FDA approves ELF
9:49 - ELF (and other NITs) will improve risk stratification by replacing ordinal Fibrosis scores with continuous test results
11:37 - Louise Campbell raises the issue of testing for the increasing NAFLD/NASH prevalence in Third World countries with fewer resources than the West has
13:02 - Ian notes that widespread population screening must start with a simple, inexpensive test, even in wealthier countries
14:54 - Roger Green raises the value of visual (picture) test results and asks how blood-based tests can overcome the fact that they do not produce pictures. Discussion and friendly debate about relative value of risk scores and visual outputs ensues.
18:39 - Ian discusses his work on patients' understanding of cirrhosis, which demonstrates the value of nursing in cirrhosis care clinics. Louise amplifies his point.
22:34 - Wrap-up question for Ian's interview
24:20 - Conversation with Michelle Long begins
26:49 - MIchelle's event: Stephen Harrison and Naim Alkhouri's paper on "Prospective Evaluation of the Prevalence of Fatty Liver Disease and NASH in an Unselected Middle-age Cohort"
28:28 - MIchelle mentions NAFLD/NASH prevalence rates among study participants
32:35 - Louise revealed what she learned in a high-level qualitative scan of patient records
33:36 - Louise discusses recent paper on the long-term of simple steatosis
35:27 - Louise wonders about the level of NAFLD/NASH education and awareness among endocrinologists.
40:10 - Louise raises the idea of scanning patients who have come to physician for other procedures, just as Stephen did in the prevalence study
44:56 - Conversation with Manal Abdelmalek begins
47:40 - Manal's event: NIH funding the new liver cirrhosis network
49:22 - Manal focuses on the urgency of doctors and patient today, the need to propose helpful therapies. At 50:30, she discusses a recent single-dose 1000mg metformin study checking its effect on portal pressure in patients with cirrhosis.
53:35 - Manal notes that statins, beta blockers have some reported positive effects in cirrhosis
56:27 - Roger raises the idea of maintaining fibrosis level as a clinically meaningful endpoint for approval
59:28 - Louise describes a way that even general practice physicians can track cirrhosis using their FibroScan machines or other equipment
1:03:19 - Manal raises the idea that this is drug help we can provide for some patients now, before approval
1:07:19 - Closing question for the third conversatio

Jörn Schattenberg joins Stephen Harrison and Roger Green to review some highlights from last week's Paris NASH meeting. This conversation looks at the Day Two sessions and the overall implications of the meeting.

Paris NASH is a meeting for basic science and interdisciplinary thinking. While the first two conversations of this series focused specifically on one or two sessions, this one takes a broader view and searches for high-level lessons and questions. From the second day, Jörn Schattenberg chose to mention several talks he felt made particularly important points and a session "NASH Around the World" that demonstrate the scale of the global challenge by looking at major countries around the world. Finally, Stephen Harrison and Roger Green joined Jörn in selecting one key takeaway from the meeting and our conversation.

Jörn Schattenberg joins Stephen Harrison and Roger Green to review some highlights from last week's Paris NASH meeting. This conversation looks at the session covering fibrosis.

Paris NASH is a meeting for basic science and interdisciplinary thinking. Since Stephen Harrison was drafted into co-chairing the session titled "Deep Dive into Fibrosis," he led this conversation. The session included three presentations with a powerful collective message about stellate cells: that different stellate cell subtypes perform in unique ways in terms of how they function, the process(es) through which they become modified and what this represents in terms of performance. This description does not do Stephen and Jörn's comments justice. It's a short session, so listen for yourself...

Jörn Schattenberg joins Stephen Harrison and Roger Green to review some highlights from last week's Paris NASH meeting. This conversation looks at sessions covering epidemiology, public response and clinical questions.

Paris NASH is a meeting for basic science and interdisciplinary thinking. As Jörn Schattenberg reviews the first two sessions of the meeting, he covers both these territories. The first session started with Professor Jeffrey Lazarus discussing some of the same issues he covered as our guest on S2 E40 of SurfingNASH. The other presentations in the first session covered economic theory and automated care models, which led Stephen Harrison to share his own thoughts on the importance of building an integrated model for clinical trials. The second session of Paris NASH discussed clinical aspects of disease. Jörn focused on a paper discussing how NASH itself varies among different patient phenotypes and what that could imply in terms of diagnostics, patient treatment and drug development.

Jörn Schattenberg joins Stephen Harrison and Roger Green to review some highlights from last week's Paris NASH meeting, an event with exciting scientific messages and insights.

If you missed last week'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. 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

Donna Cryer joins the Surfers to discuss how the COVID-19 Delta Variant is affecting Fatty Liver Disease in 2021.  This conversation focuses on the current and potential impact of the Delta and future variants on clinical trial performance. 

Seventeen months ago, Surfing the NASH Tsunami began as a podcast focused on how COVID-19 and the pandemic would affect NASH clinical trials. Some 90 original episodes later, we return to this subject in this conversation. Roger Green asks questions about how COVID-19 has affected clinical trial conduct in the US and other major markets and the rest of the Surfers provide answers about the current and future benefits from what we have learned managing trials in this pandemic. Keep listening to hear some potentially sobering comments on the effect Delta or a possible more potent future variant might have on patient recruitment and assignment. At the end, the four panelists all discuss one point listeners should take away from this conversation.

Donna Cryer joins the Surfers to discuss how the COVID-19 Delta Variant is affecting Fatty Liver Disease in 2021. This conversation focuses on vaccine confusion (taking the flu vaccine, the meaning of full approval) and the importance of global COVID-19 vaccine equity and policies that support it.

This conversation has several moments of debate, one around the likely strength of flu season in the US and another around how strong the impact of Pfizer/BioNTech's full FDA impact is likely to be in the US. On the flu discussion, Stephen Harrison follows up Donna Cryer's advocacy for all patients to take the flu vaccine by suggesting that the US will have a light flu season this year. The group does on to debate how much impact full vaccine approval is likely to have in the US and what will drive the increase in vaccinations that does occur. Finally, Donna Cryer and Roger Green discuss the case for vaccine equity, with both panelists noting that the larger portion of the cost of vaccinating countries with large, underdeveloped rural populations will lie in creating the distribution systems necessary to get treatment to patient, NOT in manufacturing the vaccine.

Donna Cryer joins the Surfers to discuss how the COVID-19 Delta Variant is affecting Fatty Liver Disease in 2021. This discussion focuses on the process of moving immunocompromised and transplant patients to the front of the booster dose queue.

After Roger Green sets the preamble for this discussion of COVID-19 Delta variant and Fatty Liver Disease, Donna Cryer kicks the discussion off by discussing how immunocompromised and liver transplant patients, who had low priority for the initial COVID-19 vaccines, moved to the front of the line for the booster doses. This is a story of communication, collaboration and just plan hard work to make certain that the data necessary to make this case was completed and communicated properly.At the end of the conversation, Stephen Harrison discusses an article from Raj Reddy in the Journal of Viral Hepatitis that makes many similar points about what we have learned about the liver (with some special focus on Fatty Liver Disease) during the first year of the COVID-19 pandemic.

Jörn Schattenberg joins the Surfers to discuss drug development in cirrhosis, which evolves into a discussion about how to drive NITs forward.

Historically, NASH drug development strategy has started in advanced fibrosis with the goal of progressing to cirrhosis next. This episode suggests an entirely different approach.

The episode starts by discussing the complexities of treating cirrhosis and evolves into a discussion on why compensated cirrhosis might be the BEST place to achieve fast, successful drug development today.

Key moments include:

10:12 - Why discuss cirrhosis?

11:40 - Challenges in cirrhosis treatment and drug development

13:08 - A changing viewpoint on cirrhosis as drug development target

17:24 - NASH and cirrhosis disease progression

20:10 - Diagnosing and stratifying cirrhosis patients

24:20 - NITs might make cirrhosis a better drug development target than F2/3

30:06 - Building momentum to reconsider NASH and cirrhosis drug development

33:47 - Identifying the conceptual road block in the move toward NITs in cirrhosis

39:09 - Formulating a plan of action to strengthen cirrhosis drug development and treatment

40:53 - A "disruptive technology" to pool clinical trial results

44:28 - The challenge: pushing cirrhosis treatment and drug development forward

50:09 - Business section