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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.

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 and comment on several other topics.Lars Johansson's Paris NASH presentation, "Innovations in Imaging Assessment of Fibrosis"," introduced his audience to a dynamic, multidimensional view of tools that can show us how the liver works. Rather than focusing on static measurements of "what shouldn't be there," Lars discusses the measurement of "what should" - for example, the interplay of fibrosis and fibrogenesis. Most striking, he describes an array of leading edge and state of the art imaging techniques that shift focus from today's "what shouldn't" targets (fat and fibrosis) to "what should" (functioning hepatocytes, to give one example.) This different viewpoint combines with the novel imaging tools and approaches to create an episode that might leave you repeatedly thinking "Oh, Wow!" Expected to be challenged and exhilarated!Highlights include:12:27 - Stephen Harrison introduces Lars Johansson by discussing the Paris NASH meeting and the session Stephen chaired14:29 - Lars begins his discussion of the Paris NASH paper15:35 - The role of PET tracers in assessing disruptions in liver homeostasis through assessment of hepatic stellate cells and imaging collagen Type I17:58 - Why Stephen sees the kinds of imaging Lars describes as "potentially a game changer" and his "next step": to associate these results with blood-based biomarkers 20:59 - Lars discusses the best interplay of circulating blood biomarkers and PET tracers, and highlights combination therapy development as an area for development22:29 - Stephen suggests that this approach can provide more holistic solutions than histopathology, particularly for metabolic disease and specific sub-types25:04 - Louise discusses the benefit to the patient of using these kinds of technique to move beyond much current biopsy26:25 - Lars's "second piece from Paris" is the use of a gadolinium contrast agent due to its high level of hepatic uptake27:41 - Roger observes that these tools allow us to study the liver as a dynamic system28:24 - Lars discusses why to him, hepatocyte function  is a robust dynamic measure 29:38 - Stephen speculates that these techniques can create knowledge more efficiently than our best measures today and suggests that they will provide greatest value in cirrhosis and advanced fibrosis34:32 - Lars suggests these kinds of techniques might replace for augment HVPG over time and goes on to share an integrated version of how much data these approaches can produce in a single drug trial 36:22 - Louise's "Dare to Dream:" replace biopsy with an easier way to assess path of disease which will allow more efficient screening of more patients37:12 - Roger's "Dare to Dream:"  visualize the liver in the context of the whole patient39:23 - Stephen's "Dare to Dream:" to become cognizant of  how the range of noninvasive tests can help us mold drug development for different phenotypes of patients and separately,  to speed drug development41:09 - Lars's "Dare to Dream:" Bring these techniques to early drug development, which will streamline investment of time and money by improving focus 42:52 - Roger's final question - "The one thing that 'blew everyone's minds' the most."46:40 - Business Section - A listener record; for the first time, a conversation gets more downloads than its episode, update on CME, requests for conferences you would like us to attend

Last author and leading endocrinology Fatty Liver Opinion Leader Ken Cusi joins co-author Stephen Harrison, Louise Campbell and Roger Green to discuss the recent Clinical Care Pathway published in Gastroenterology. This conversation answers the question "What Can Be Done Today?" in terms of screening and patient management without approved drugs.The paper "Clinical Care Pathway for the Risk Stratification and Management of Patients with Nonalcoholic Fatty Liver Disease" is a clarion call to action, but what exactly should clinicians do? This conversation addresses that issue. Louise Campbell starts by stating that the World Health Organization should incorporate Fatty Liver disease into their diabetes initiative. Next, she leads the group into a discussion of the merits of transient elastography, which leads Ken Cusi and Stephen Harrison to discuss blood-based and imaging options clinicians can deploy when they lack access to a FibroScan or similar device. Finally, Roger asks the most important step stakeholders should take now, which provide an array of different actions.

Last author and leading endocrinology Fatty Liver Opinion Leader Ken Cusi joins co-author Stephen Harrison, Louise Campbell and Roger Green to discuss the recent Clinical Care Pathway published in Gastroenterology. This conversation centers on two issues: driving behavior change and recognizing the scope of the need.For "Clinical Care Pathway for the Risk Stratification and Management of Patients with Nonalcoholic Fatty Liver Disease" to achieve its goals, clinicians need to be motivated to action and then understand what to do and why. This conversation discusses different philosophical and behavior economics motivators. Ken Cusi stated his excitement based on the belief that once a clinician starts to screen and sees one seemingly healthy patient with cirrhosis, he will treat differently. Roger Green pointed out three small items in the first paragraph of the paper that seem designed to say, "This is serious. Pay attention!" Finally, Ken and Stephen Harrison discuss their previous work in assessing prevalence, which demonstrated that disease is far more widespread than most people (clinicians and patients alike) believe and over the past 10 years, we may be seeing a dramatic increase in the number of seemingly healthy people with severe NASH.

Last author and leading endocrinology Fatty Liver Opinion Leader Ken Cusi joins co-author Stephen Harrison, Louise Campbell and Roger Green to discuss the recent Clinical Care Pathway published in Gastroenterology. This conversation centers on how the working group came to be and how they developed this pivotal paper.The path to publishing "Clinical Care Pathway for the Risk Stratification and Management of Patients with Nonalcoholic Fatty Liver Disease" had its challenge, both in terms of forming the working group and then working through the key issues and questions for the paper. In this conversation, last author Ken Cusi addresses the first point and co-author Stephen Harrison addresses the second one. Between the two, Louise Campbell comments on how important this paper is to the future of Fatty Liver diagnosis and treatment.

Last author and leading endocrinology Fatty Liver Opinion Leader Ken Cusi joins co-author Stephen Harrison, Louise Campbell and Roger Green to discuss the recent Clinical Care Pathway published in Gastroenterology.Last week, Gastroentrology published the article "Clinical Care Pathway for the Risk Stratification and Management of Patients with Nonalcoholic Fatty Liver Disease.This paper and its predecessor, "Preparing for the NASH Epidemic: A Call to Action," was the result of collaboration between leaders in endocrinology, diabetes care, bariatric medicine and obesity care, primary care, gastroenterologists and hepatologists. This paper presents a clear, straightforward multidisciplinary pathway for the identification, screening, diagnosis, risk stratification and management of NAFLD and NASH patients. It is truly a groundbreaking piece of work.Dr. Kenneth Cusi, who served as last author on both papers, joins the Surfers to discuss the effort that went into development of the pathway and critical elements for its adoption and use.Highlights include:7:40 - Ken Cusi begins to discuss his history with Stephen Harrison and work on the Clinical Care Pathways paper10:41 - Louise Campbell's initial reaction: "A pivotal piece"12:29 - Stephen Harrison discusses the way the group worked together13:54 - Ken's first goal: "to build the muscle" for non-hepatologists to think about Fatty Liver whenever treating a patient in the three targeted groups17:26 - Stephen identifies a key discussion point in the group: identifying at-risk patients to target18:48 - Why the group chose FIB-4 as its initial standard test20:57 - Ken's hope: medical societies asking their clinician members to screen the three groups regularly for Fatty Liver22:42 - Three items that struck Roger Green immediately22:35 - Ken's "down to earth" study of asymptomatic patients25:38 - Increasing awareness might drive two changes in prescribing behavior: doctors might select diabetes drugs with the liver in mind and not stop the patient's statins26:46 - Stephen reviews the 2021 San Antonio prevalence study29:54 - Stephen: What's changed since the 2011 San Antonio prevalence study? Moderate-to-severe NASH more than doubled!32:00 - Louise: liver disease should become part of the WHO initiative on diabetes33:07 - Ken explains elastography in simple terms35:10 - Stephen discusses principles of screening for NASH patients with significant cirrhosis risk36:07 - Stephen lists blood-based and imaging confirmatory options for clinicians who cannot access FibroScan or other in-office elastography38:11 - Roger: How does this translate into the last 5 or 10 patients a clinician saw?39:20 - Ken expresses optimism that new obesity drugs will motivate non-hepatologists to look for NASH harder and treat it more aggressively40:41 - Louise raises two more questions42:14 - Stephen's closing comments: we're at the beginning, like the Wright Brothers43:32 - Louise's closing comments: education, education, education...and advocacy44:22 - Ken's closing comments: share hepatologists' knowledge with other specialties to improve screening and care of Fatty Liver disease46:04 - Roger's closing comment: if a journey of 1,000 miles starts with a single step, this is like starting with a marathon47:17 - Business report -- CME credits for Surfing the NASH Tsunami, the reason for two sponsors and an exciting schedule ahead

Mazen Noureddin joins Stephen Harrison, Louise Campbell and Roger Green to close our series of "Biggest Stories of NASH Summer." In this conversation, Roger uses a classical Marketing Research question to help the group sort out the relative impact potential of the ideas they have been discussing.This conversation starts with Roger Green using an old marketing research question. He asks each panelist to divide 100 points of potential to change between Stephen's multi-slide concept, drug development as exemplified by the EFX trial and advances in NITs as exemplified by MRE. The group each comes to different answers and uses different logic to get there. Listen to their thinking to decide what you can learn from each of them and where you disagree.

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.

Mazen Noureddin joins Stephen Harrison, Louise Campbell and Roger Green to close our series of "Biggest Stories of NASH Summer." In this conversation, Stephen Harrison starts by discussing some issues and insights around the use of FGF-21s and then "hijacks" the conversation to explore a standard practice in histopathology that he would like to change.This conversation starts with Stephen talking about the differences between FGF-21s and discussing why these results are so compelling. He asks Mazen to comment on how he expects to use FGF-21s in practice and Mazen provides a thoughtful, nuanced reply.At this point, Stephen shifts gears to ask why we do not produce more slides from a given liver sample. He and Mazen agree that they have wondered about this for a while and believe it would strengthen results. Speaking from more of a straight statistical perspective, Roger Green agrees.

Mazen Noureddin joins Stephen Harrison, Louise Campbell and Roger Green to close our series of "Biggest Stories of NASH Summer." In this conversation, Stephen Harrison provides an image to suggest the enormity of the coming NASH pandemic and Mazen identifies his two biggest stories of summer.Mazen's "biggest things of summer" include Stephen's recent article on the efruxifermin Phase 2a trial that was published in Nature and the Mayo Clinic group's work on MRE. For the efruxifermin, he cites some remarkably positive trial results, with a second related point. The study was published in Nature Medicine, which is only now and its various publications are now looking to publish original clinical trial research on NASH and Fatty Liver disease. To Mazen, this demonstrates the growing focus on NASH as a coming challenge.Earlier in this conversation, Stephen makes the same point a different way by noting that according to estimates published by some of our leading hepatologists, the number of NASH-related deaths from 2016-2030 in the US will dwarf the number of COVID-19 deaths to date.On Mazen' second point, he discusses why MRE is such an important diagnostic testing method for clinical trials and why papers like this one will be so critical in moving "Beyond the Biopsy."Stephen wraps up this conversation by noting how quickly Fatty Liver research and knowledge are developing on multiple paths, all in common.

Mazen Noureddin joins Stephen Harrison, Louise Campbell and Roger Green to close our series of "Biggest Stories of NASH Summer" with his own unique slant on recent events and publications.Mazen's take on the 'Biggest Stories of NASH Summer" integrates the content of papers, the journals in which they were published and the attention they received to form a message that says, "Fatty Liver has more good news to report and more people who want to learn about it." Halfway through, Stephen Harrison "hijacks" the episode to ask a common sense question about how the Fatty Liver community uses slides from biopsies today. This leads to a conversation in which each participant comes at the issue from a dramatically different angle.Highlights include:8:49 - Mazen Noureddin begins to discuss his "Biggest Stor(ies) of Summer"9:54 - Mazen focuses specifically on the efruxifermin (EFX) paper in Nature Medicine12:56 - Mazen shifts focus to the recent paper from the Mayo Clinic group that used a retorspective study of MRE results and longer-term outcomes to demonstrate that MRE improve prognosis accuracy in CLD patients15:24 - Stephen Harrison begins his response to Mazen16:45 - Stephen discusses what he considers the most important lessons from the EFX trial18:33 Mazen on where FGF-21s are likely to be used and what what duration22:21 - Stephen "hijacks" the discussion to raise the idea of one H & E slide per biopsy.25:12 - Mazen agrees with Stephen's statement about multiple slides26:51 - Roger concurs from a probability sampling point of view27:18 - Louise begins her reply by discussing the impact of side effects on patients, using Hep C as an earlier example, and the hope that clinical trials can more closely resemble care in everyday practice29:06 - Stephen comments on why trials and clinical practice are so different and why it continues to be this way31:38 - Mazen discusses FGF-21 side effects in the context of GLP-1s32:47 - Louise notes that biopsy samples are valuable and costly to the patient (in terms of discomfort, at least) and that we show the patient respect by extracting the maximum possible value from each tissue sample33:31 - Roger asks the historical logical for doing only one H & E slide per patient. Mazen speculates, then Stephen explains.37:05 - Roger asks whether the goal is to improve screen fail rates and reduce placebo scores at the same time. Stephen confirms this.37:58 - Roger asks group to assign scores to the relative importance of multiple slides, new medications and moving to NITs. Answers vary. The reasons are even more interesting than the answers themselves

Professor Manal Abdelmalek joins Louise Campbell and Roger Green to discuss the important Fatty Liver stories of the last few months. She focuses on NIH's recent decision to stand up and fund the Liver Cirrhosis Network.To Dr Abdelmalek, the NIH action signifies increased focus on the significant long-term consequences of Fatty Liver disease. She discusses a Q&A at a talk she gave this summer where a physician noted that drug development is exciting but three years in the future and asked, "What can I do for my patients NOW?" She cites a recent small, early-stage study that suggested a single dose of metformin might have an impact on portal pressure and goes on to suggest that statins and beta blockers might also have a role to play in treating compensated cirrhosis patients. Louise Campbell contributes a strategy for evaluating patients taking these older drugs using FibroScan and blood-based tests. This is an innovative way to look at providing immediate benefit for patients who need it most urgently.

Professor and epidemiologist Michelle Long joins Louise Campbell and Roger Green to discuss the important Fatty Liver stories of the last few months. She focuses on the recent paper on prevalence of NAFLD and NASH in an unselected middle-aged population.To Dr. Long, an epidemiologist, there has been very little high quality perspective research on NAFLD/NASH prevalence. She discusses why she considers the study a methodological advantage. She and Roger Green agree that the conventional wisdom, which posits a 25% incidence of NAFLD and that 25% of NAFLD patients have NASH, is probably far too low. Instead, they note, a more realistic NAFLD estimate might be 37% NAFLD and a more realistic NASH estimate might be 14%. This suggests a far greater need to screen quickly and aggressively across most patient segments. At that point, Louise Campbell joins the conversation to suggest a strategy to screen faster and more efficiently. All things considered, this conversation increases the salience of diagnosing and treating Fatty Liver disease and some ways to find patients.

Newly-appointed Professor Ian Rowe joins Louise Campbell and Roger Green to discuss the important Fatty Liver stories of the last few months. He focuses on the recent FDA approval of the ELF test for prognosis of cirrhosis.To Professor Rowe, the ELF approval was the most important story of summer because it promises a brighter future for non-invasive tests and, eventually, decreased reliance on biopsy. Dr. Rowe points out that transitioning from the ordinal results that biopsy generates (fibrosis score level) provide limited, unrealistic guidance in determining the probability of a downstream negative event (transplant, cancer, death). He contrasts this to continuous test results, including blood-based and device-driven tests, which provide clearer guidance about downstream risks. Louise Campbell adds her own reflections about the importance of inexpensive, blood-based tests to address the emerging NASH pandemic in poorer Third World Countries. This is not a long conversation, but it looks at the issue from some unusual, enlightening angles.

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 announcement6:31 - Ian's event: FDA approves ELF9:49 - ELF (and other NITs) will improve risk stratification by replacing ordinal Fibrosis scores with continuous test results11:37 - Louise Campbell raises the issue of testing for the increasing NAFLD/NASH prevalence in Third World countries with fewer resources than the West has13:02 - Ian notes that widespread population screening must start with a simple, inexpensive test, even in wealthier countries14:54 - 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 interview24:20 - Conversation with Michelle Long begins26:49 - 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 participants32:35 - Louise revealed what she learned in a high-level qualitative scan of patient records33:36 - Louise discusses recent paper on the long-term of simple steatosis35:27 - 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 study44:56 - Conversation with Manal Abdelmalek begins47:40 - Manal's event: NIH funding the new liver cirrhosis network49:22 - 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 cirrhosis56:27 - Roger raises the idea of maintaining fibrosis level as a clinically meaningful endpoint for approval59:28 - Louise describes a way that even general practice physicians can track cirrhosis using their FibroScan machines or other equipment1:03:19 - Manal raises the idea that this is drug help we can provide for some patients now, before approval1:07:19 - 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.