Surfing the MASH Tsunami

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In yet another topical debut, Surfing NASH explores pediatric and adolescent Fatty Liver disease, its alarming prevalence and developing the field's understanding around how to treat this vulnerable subpopulation. The Surfers are joined in discussion by Naim Alkhouri and chief of Gastroenterology, Hepatology and Nutrition at Children’s Hospital Los Angeles, Rohit Kohli for a special session which illuminates a critical issue intimate to the two extremely knowledgeable guests.

Roger Green prefaces this conversation with the observation that as a pandemic of Fatty Liver disease grows at boggling speed, so too does NAFLD and NASH in younger populations. While this recognition may in part be attributed to improved methodologies, it is evident that lifestyle norms around diet and exercise continue to exacerbate the problem. Rohit expands on the notion that an environmental shift has contributed to the dilemma, referring to the emergence of accessible, low cost, calorically-loaded processed foods that are not only to be available at home but also within schools. He refers to a study of a controlled cohort on incidence of NAFLD in children from 2009-2018. Strikingly, it was determined that the incidence of NAFLD diagnosis significantly increased over time from 36.0 per 100,000 in 2009 to 58.2 per 100,000 in 2018 (P < .0001). Still, many children may remain undiagnosed. Roger comments on the potential of geopolitical events during this study that could influence shift of a nutritional landscape. 

Naim adds that estimates around prevalence also increase when considering adolescents as opposed to children. He highlights that 17-25% of adolescents are suffering from “not just NAFLD, but actually NASH and significant fibrosis.” A combination of genetic backgrounds and complicating conditions ranging from obesity to sleep apnea are entangled with disease progression. Lastly, Naim shares a sobering anecdote from his clinic of a 13 year-old patient with biopsy-proven cirrhosis.

If you have questions or interest around pediatric and adolescent Fatty Liver disease, we kindly ask that you submit reviews wherever you download our discussions. Alternatively, you can write us directly at [email protected]. 

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In yet another topical debut, Surfing NASH explores pediatric and adolescent Fatty Liver disease, its alarming prevalence and developing the field's understanding around how to treat this vulnerable subpopulation. The Surfers are joined in discussion by Naim Alkhouri and chief of Gastroenterology, Hepatology and Nutrition at Children’s Hospital Los Angeles, Rohit Kohli. This is a special session which illuminates a critical issue intimate to two extremely knowledgeable guests. Rich with invaluable insights, the panelists elaborate on the following major themes:

08:55
Roger Green prefaces this conversation with the observation that as a pandemic of Fatty Liver disease grows at boggling speed, so too does NAFLD and NASH in younger populations. While this recognition may in part be attributed to improved methodologies, it is evident that lifestyle norms around diet and exercise continue to exacerbate the problem. Rohit expands on this notion by sharing apt research examples which demonstrate swelling prevalence in younger populations. He suggests that while methodologies have improved, we are indeed witnessing increasing incidence. Most strikingly, Naim refers to an anecdote witnessed in his clinic of a 13 year-old patient with biopsy-proven cirrhosis.

16:05
Jörn Schattenberg steers discussion toward the cardiometabolic implications behind patients living longer with Fatty Livers. Naim describes a paper he co-authored which sought to strengthen understanding of epidemiology by histopathology reports in Sweden. With access to virtually all liver biopsies in the country, the group set out to identify cardiovascular disease emerging in patients previously diagnosed with NASH under the age of 25. He details results which underscore a swathe of associations linking Fatty Liver to metabolic complications. Rohit adds comments around the role and appropriateness of bariatric surgery in adolescents to mitigate the long-term metabolic consequences of obesity. Louise Campbell prompts explanations around histopathological differences in adolescents versus adults, and what's unique in the application of NITs for younger patients. 

28:37
The group continues to consider how to accelerate clinical trial learnings into real world implementations. This develops into ideas around effectively introducing lifestyle interventions to children at a societal scale. It's noted and agreed that nutritional matters are family matters. Rohit describes guidelines which utilize annual physicals with adolescents as an opportunity to track liver health. Naim goes on to describe elements contributing to our understanding of early life risk and natural history of disease.

38:22
As the session winds down, Roger asks the panelists for what impact they envision emerging trials and drugs to have in the pediatric space. Each provides thought-provoking responses and Louise raises grave concern over coping with the enormous industry influence on the milieu of nutrition surrounding children. Listen to the full feature to hear the various reactions.

If you enjoy this episode, have questions or interest around pediatric and adolescent Fatty Liver disease, we kindly ask that you submit reviews wherever you download our discussions. Alternatively, you can write us directly at [email protected].

Stay Safe and Surf On!

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This week, SurfingNASH is offering conversation segments to showcase our new series, The NASH Tsunami in Diabetes: Getting Ahead of the Rising Tide. Rising Tide, as we call it, is a subscription-only series targeted at the primary care physicians, endocrinologists and allied health professionals who provide front-line treatments for patients living with Type 2 Diabetes and/or obesity. In this episode From the Vault,  Jeff Lazarus and Roger Green discuss the ease of creating valuable metrics in a comprehensive care model, while our three practitioners -- Stephen Harrison, Jörn Schattenberg and Louise Campbell -- dive further into how they believe this model will improve care.

KEY POINT: Broadening the number and diversity of health care providers assigned to each individual patient will improve care by improving focus on the areas that count. It is important that system designers ask the right questions and answer them rigorously in context; it is undesirable for the systems to look more or less identical.

If you enjoy episode 9 and its introduction to Rising Tide, please visit our website and sign up to listen to the full discussions and more exclusive content. We also kindly ask that you submit reviews wherever you download our discussions or, alternatively, write to us directly at [email protected].

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This week, SurfingNASH is offering conversation segments to showcase our new series, The NASH Tsunami in Diabetes: Getting Ahead of the Rising Tide. Rising Tide, as we call it, is a subscription-only series targeted at the primary care physicians, endocrinologists and allied health professionals who provide front-line treatments for patients living with Type 2 Diabetes and/or obesity. This sample session comes from the just-released Season 2 debut which focuses comprehensively on a new chapter of the podcast and why 2023 might be “the best year ever” for Fatty Liver.

The group considers what made 2022 special. Mazen highlights Madrigal’s positive topline results from the Phase 3 trial of resmetirom for treatment of NASH and liver fibrosis. He also notes Intercept’s study on evaluating the safety and efficacy of obeticholic acid in patients with compensated cirrhosis. Ken underscores the development of algorithms for identifying and diagnosing patients. He is optimistic about different societies aligning to define pathways because NAFLD and NASH are metabolic diseases at the center of converging fields. Roger states his highlight of 2022 to be movement toward noninvasive tests and away from biopsies.

Conversation expands on the NASH drug pipeline. Mazen cites utility in GLP-1 medications, like semaglutide, and the pan-PPAR agonist, lanifibranor. Roger adds that efruxifermin, an FGF21, has the potential to regress fibrosis in pre-cirrhotic patients. Ken notes it was previously thought that a monotherapy would cure NASH. Today, the promise of combination therapies demonstrates benefits which positively impact weight and other cardiometabolic variables. Roger echoes the idea that the ability to stop progression and reduce steatosis is an achievable target today.

Shifting to diagnostics, Roger explains the fading narrative of biopsy as a gold standard. Mazen emphasizes need to screen Type 2 diabetics and those with two or more metabolic risk factors. He introduces a simple test, called FIB-4, which helps to estimate the amount of scarring in the liver. FIB-4 is a basic computation that factors a patient’s age, liver enzymes and platelet count. He also describes transient elastography FibroScan, a noninvasive method evaluating liver fibrosis by measurement of liver stiffness. Lastly, he details the enhanced liver fibrosis (ELF) test, a blood test that provides a score reflecting the severity of liver fibrosis. A key message: patients with Stage 2 fibrosis and higher need to be referred as this is the population with significant risk of facing severe complications. Ken builds on the idea behind criticality in screening and identifying early in disease progression. There are simply not enough hepatologists to treat the millions of patients with liver disease.

After more notes around guidelines and practical, systemic approaches to navigate widespread prevalence, the panelists offer closing comments. The final points focus on: 1) biggest takeaways for frontline treaters, and 2) most exciting elements to emerge in this space in 2023.

If you enjoy this preview, please visit our website and sign up to listen to the full episode and more exclusive content. We also kindly ask that you submit reviews wherever you download our discussions or, alternatively, write to us directly at [email protected].

The Rising Tide podcast series and all episodes are produced under a non-restricted grant from Novo Nordisk. Novo Nordisk has neither influenced nor reviewed the contents of this podcast in any way. This content represents the views of the speakers and does not necessarily represent the views of Novo Nordisk. The content herein is for educational purposes only and should not be taken as medical advice.

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This week, SurfingNASH is offering conversation segments to showcase our new series, The NASH Tsunami in Diabetes: Getting Ahead of the Rising Tide. Rising Tide, as we call it, is a subscription-only series targeted at the primary care physicians, endocrinologists and allied health professionals who provide front-line treatments for patients living with Type 2 Diabetes and/or obesity. This preview looks at drug choices prescribers can make today for patients with Type 2 Diabetes Mellitus and obesity that have positive impact on Fatty Liver disease. In addition to co-hosts Dr. Ken Cusi and Roger Green, panelists for this discussion include endocrinologist Dr. Scott Isaacs, second author of the recent AACE guidelines, and hepatology researcher Dr. Naim Alkhouri.

Ken notes that we are living in a period where the paradigm around treating chronic metabolic conditions is shifting. In a world where one in five patients with T2DM lives with clinically significant fibrosis, Ken states providers can no longer ignore the liver when making treatment decisions about diabetes. He also suggests that hepatologists need to become more comfortable using medications that were previously reserved for diabetes.

At this point, Naim and Scott join the conversation. Naim begins by discussing EDICT, a trial that compared the standard T2DM regimen of the day (metformin, followed by the sulfonylurea glipizide and then insulin) to a first-line combination therapy of metformin, the GLP-1 agonist exenatide and the PPAR pioglitazone. At the end of this six-year period, the researchers found meaningful, statistically significant differences in three key Fatty Liver parameters: prevalence of NAFLD (69% vs. 31%); clinically significant fibrosis (26% vs. 7%); and percentage fat in the liver (12.5% vs. 8.5%). It also found that patients achieved a lower HbA1c level (6.0% with the combination, vs. 6.8% in the standard treatment group).

In response to a question from Roger, Ken identifies three majors lessons of the last 10 years:

7 of 10 Americans with T2D have a fatty liver; those with NAFLD but not T2D see their chances of becoming diabetic and , separately, developing cardiovascular disease double.

15-20% of Americans with T2D also exhibit moderate-to-advanced cirrhosis.

GLP-1s, as a class, address multiple factors of chronic metabolic disease. They reduced HbA1c, promote and maintain significant weight loss, and slow progression of fibrosis.

Naim expresses a concern that many doctors treating patients with T2D do not consider NASH. A Cleveland Clinic assessment of ICD-10 codes demonstrated that only 5% of T2D patients were coded for NAFLD. This means the 2/3 of the T2D patients in that system have fatty livers and were never evaluated! Similarly, ~2/3 of the patients who present with cirrhosis in his clinic were never told that they had NAFLD. In Naim’s view, NAFLD should be a disease for primary care and endocrinology to treat, while it should be hepatologists that treat NASH.

If you enjoy this preview, please visit our website and sign up to listen to the full episode and more exclusive content. We also kindly ask that you submit reviews wherever you download our discussions or write to us directly at [email protected].

The Rising Tide podcast series and all the episodes are produced under a non-restricted grant from Novo Nordisk. Novo Nordisk has neither influenced nor reviewed the contents of this podcast in any way. This content represents the views of the speakers and does not necessarily represent the views of Novo Nordisk. The content herein is for educational purposes only and should not be taken as medical advice.

Send us Fan Mail

This week, SurfingNASH is offering conversation segments to showcase our new series, The NASH Tsunami in Diabetes: Getting Ahead of the Rising Tide. Rising Tide, as we call it, is a subscription-only series targeted at the primary care physicians, endocrinologists and allied health professionals who provide front-line treatments for patients living with Type 2 Diabetes and/or obesity. This preview comes from our second episode which focused on the new AACE Fatty Liver Guidelines.

The panelists include four authors of the guidelines: first author Dr. Ken Cusi from the University of Florida, third author Dr. Diana Barb, also from the University of Florida, and the two leading AASLD representatives in this project, Dr. Zobair Younossi of INOVA Health Systems and Dr. Maru Rinella of the University of Chicago. Dr. Younossi focuses his discussion on the epidemiology of the disease and what it suggests in terms of treatment goals and priorities. Dr. Cusi identifies the two main messages of the guidelines: the importance of FIB-4 as a screening tool and the fact that even today, with no recently approved NASH drugs on the market, there are therapeutic choices providers can make that will benefit NASH patients. Dr. Barb discusses in detail prescribing decisions that can benefit diabetes patients at risk of progressing to significant NASH fibrosis and beyond. Dr. Rinella lends comments throughout from her own perspective and that of AASLD. This fast-paced episode provides a tremendous amount of information while remaining accessible and easy to follow.

If you enjoy the preview, please visit our website and sign up or sign in to listen to the full episode and more exclusive content. We also kindly ask that you submit reviews wherever you download our discussions or, alternatively, write to us directly at [email protected].

The Rising Tide podcast series and all the episodes are produced under a non-restricted grant from Novo Nordisk. Novo Nordisk has neither influenced nor reviewed the contents of this podcast in any way. This content represents the views of the speakers and does not necessarily represent the views of Novo Nordisk. The content herein is for educational purposes only and should not be taken as medical advice.

Send us Fan Mail

This week, SurfingNASH is offering conversation segments to showcase our new series, The NASH Tsunami in Diabetes: Getting Ahead of the Rising Tide. Rising Tide, as we call it, is a subscription-only series targeted at the primary care physicians, endocrinologists and allied health professionals who provide front-line treatments for patients living with Type 2 Diabetes and/or obesity.

This sample session comes from the debut episode which focuses on research that has led AACE to issue guidelines, AGA to propose clinical care pathways and AHA to produce a white paper on the links between Fatty Liver Disease and CVD Risk. Endocrinology researcher and key opinion leader Ken Cusi discusses his work looking at NAFLD and NASH in diabetic patient populations. He covers studies confirming that patients with diabetes are at least twice as likely to have NAFLD or NASH as non-diabetics. He notes that this effect is confirmed in overweight as well as obese patients and is proven independent of obesity (an important note: the two together are worse than either alone). In practical terms, he asserts that primary care and endocrinology clinics are the places we can identify NAFLD and early NASH before these become later-stage fibrosis or cirrhosis requiring attention from hepatologists. In that context, he notes that twice as many patients in an endocrinology clinic will test positive for NAFLD or NASH compared to a primary care clinic, thus making endocrinologists a vital target group for earlier identification and treatment of Fatty Liver Disease. In his practice, Ken advocates for every patient to receive a FIB-4 test, which can be found in most EMR systems and is an inexpensive, reasonably reliable negative predictor for F3 or F4 status.

Next, hepatology researcher and key opinion leader Kathleen Corey discusses some of her research on the link between CVD and NAFLD. Two key conclusions: over a relatively short period after initial induction into the study (median of 25.5 months), the presence of NAFLD causes a 70% increase in relative risk (4.1% vs. 2.6%) of a Major Adverse Cardiovascular Event (MACE). She agrees with Ken’s suggestion about FIB-4. She also notes the trend of primary care physicians to discontinue statins if the patient’s ALT level starts to rise and cautions that this step is likely to increase patient risk.

Finally, Kay Pepin, Director of Research Translation for Resoundant Inc. under joint appointment with the Mayo Clinic, discusses research demonstrating that a relatively simple MRE session can provide the information necessary to determine the likelihood that fibrosis will advance to cirrhosis or compensated cirrhosis will advance to decompensated states. She also notes that with insurance coverage, this is not an expensive test for many people. By adding a simple MRI module to the MRE session, physicians can derive a significant amount of additional information.

If you enjoy this preview, please visit our website and sign up to listen to the full episode and more exclusive content. We also kindly ask that you submit reviews wherever you download our discussions or, alternatively, write to us directly at [email protected].

The Rising Tide podcast series and all the episodes are produced under a non-restricted grant from Novo Nordisk. Novo Nordisk has neither influenced nor reviewed the contents of this podcast in any way. This content represents the views of the speakers and does not necessarily represent the views of Novo Nordisk. The content herein is for educational purposes only and should not be taken as medical advice.

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This week, SurfingNASH.com is offering a 17-minute section of our new series, “The NASH Tsunami in Diabetes; Getting Ahead of the Rising Tide.” Rising Tide, as we call it, is a subscription-only series targeted at the primary care physicians, endocrinologists and allied health professionals who provide front-line treatments for patients living with Type 2 Diabetes and/or obesity.

This conversation is an opportunity for NASH Tsunami listeners to learn about the series and why to subscribe by listening to this 17-minute segment of a previously unpublished episode from October, 2022, that is as timely today as when it was recorded.

The full episode follows the experience of Fatty Liver Alliance Founder and President Michael Betel when he submitted to extensive non-invasive diagnostic testing to determine his own Fatty Liver status. Mike’s experience, which he recorded for educational purposes and posted on Facebook, was a somewhat confusing experience due to inconsistencies in the results of various tests. In the episode, Rising Tide co-host Dr. Kenneth Cusi and episode guest (and NASH Tsunami co-host) Professor Jörn Schattenberg join Mike and co-host Roger Green to review Mike’s test results and recommend courses of action for Mike to take. In this process, the group also discusses the Fatty Liver guidelines from AASLD, AACE, AGA and others and the pivotal role that front-line screening plays in these guidelines.

This segment of the episode shares Mike’s story and some of the feedback he received from Ken, Jörn and Roger. At the end of the episode, Roger provides guidance on how listeners can subscribe to the Rising Tide series.  

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In this conversation From the Vault, panelists preview the inaugural Innovations in NAFLD Care Workshop which took place in Barcelona on May 6 and 7, 2022.  Commentary considers the bulk of the Day Two Agenda which conveyed an overall theme that NASH treatment is integrated and multifactorial. The day starts with Jeff Lazarus discussing Comprehensive Care Models for NASH, the path there and desired endpoints. The rest of Session 4 focuses on two forms of technical support: integrating non-invasive tests for NAFLD into clinical practices outside the liver space and looking at the power of apps to transform the weight management process. Session 5 focuses on pharmacotherapy, including use of current pharmacotherapy in weight loss and diabetes and some of the future agents that will come into use over the next few years. Finally, Session 6, which Roger Green will moderate, pulls together a diverse set of panelists to consider the NAFLD/NASH Roadmap in the context of social media and digital transformations. Listening to this conversation provides a clear sense of how broad the scope of Day Two issues will be.

In the interest of time, this summary does not list the names of the speakers giving each talk. This is an absolutely first-class global faculty. If you are curious, visit the meeting program to learn who these exceptional speakers are. 

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For the first time, Surfing NASH takes a deep dive into the prospect of digital therapeutics, their ability to drive outcomes and the critical success factors for proper use and deployment. This is an increasingly apt topic which intermittently surfaces on the podcast but has never featured at the center of conversation. The Surfers are joined by Naim Alkhouri and two new guests with prominent focus in this space: Joe Rubinsztain, CEO and Co-Founder of ChronWell, and Mark Berman, CMO of Better Therapeutics.

In this final session, Roger prompts the panelists to share final thoughts around how digital therapeutics will evolve over time. Each offers a unique perspective accounting for different pieces of a collective puzzle: combating Fatty Liver through technological innovation. Joe and Mark discuss where they envision their respective work to converge. Jörn and Louise offer insights which indicate that different economic structures may require various reimbursement systems and provider dynamics. While this session features ideas around both the enormous potential and daunting challenges behind the world of digital health and digital therapeutics, the panelists provide rich insights which remain optimistic. These are big questions with far-reaching implications for the future of medicine. If you enjoy this topic and would like to learn more, we kindly invite you to leave a review on your preferred listening platform. We also encourage our audience to write us questions to include your on-ground experiences and ideas in the weekly discourse. Thank you for your continued support - stay safe and surf on!