Podcasts about Fibrosis

Contributor: Ricky Dhaliwal, MD Educational Pearls: What factors are considered in a COVID-19 infection? The viral load: Understood as the impact of SARS-CoV-2 viral particles infecting host cell tissue itself (utilizing ACE-2 receptors). Pro-Inflammatory Response: Post-infection, the body's downstream systemic cytokine release (can be both normal or hyperactive, aka “cytokine storm”). What cardiac impacts have been observed with COVID-19? Arrhythmias: The mechanism of COVID-19 infection and arrhythmias is believed to be multifactorial. However, evidence suggests T-cell-mediated toxicity and cytokine storm may contribute to cardiac myocyte damage, precipitating proarrhythmias instead of direct viral entry. Bradycardia: Increased prevalence in patients with severe COVID-19 infection, but not associated with increased adverse outcomes. Atrial Fibrillation: Most common cardiac complication and risk factor for worsened outcomes in patients with COVID-19. Biggest associated risk is strokes, and may require heightened monitoring and anticoagulation therapy to mitigate stroke risk. Fibrosis of Cardiac Tissue: Similar to arrhythmias, believed to be inflammation-mediated in COVID-19. Fibrosis of cardiac tissue increases the risk that any arrhythmias that develop during infection may persist after the infection has resolved. Ventricular damage: Also inflammation mediated by an active infection and contributes to myocarditis. No evidence suggests that COVID-19 vaccination contributes to myocarditis.  Sinus node dysfunction induced by inflammation that may lead to or be similar to Postural Orthostatic Tachycardia Syndrome (POTS).  Big takeaway? Patients who have had or currently have COVID-19 are at an increased risk of developing arrhythmias and sustaining them post-infection. However, a majority of patients will recover. Due to atrial fibrillation being the most prevalent arrhythmia associated with COVID-19 infection, increased monitoring and potential anticoagulation therapy are required.  References Gopinathannair R, Olshansky B, Chung MK, Gordon S, Joglar JA, Marcus GM, et al. Cardiac Arrhythmias and Autonomic Dysfunction Associated With COVID-19: A Scientific Statement From the American Heart Association. Circulation. 2024 Nov 19;150(21):e449–65. Khan Z, Pabani UK, Gul A, Muhammad SA, Yousif Y, Abumedian M, et al. COVID-19 Vaccine-Induced Myocarditis: A Systemic Review and Literature Search. Cureus. 14(7):e27408. Summarized by Dan Orbidan, OMS1 | Edited by Dan Orbidan & Jorge Chalit, OMS3 Donate: https://emergencymedicalminute.org/donate/

Welcome to HCPLive's 5 Stories in Under 5—your quick, must-know recap of the top 5 healthcare stories from the past week, all in under 5 minutes. Stay informed, stay ahead, and let's dive into the latest updates impacting clinicians and healthcare providers like you! Interested in a more traditional, text rundown? Check out the HCPFive! Top 5 Healthcare Headlines for April 21-April 27, 2025: FDA Approves Pz-cel (Zevaskyn) Gene Therapy for RDEB The FDA has approved pz-cel, the first autologous gene therapy for RDEB, following pivotal Phase 3 data demonstrating efficacy and safety in wound healing. FDA Approves Upadacitinib, Expanding Treatment for Adults With Giant Cell Arteritis Upadacitinib has been approved for giant cell arteritis, supported by Phase 3 data showing its potential to induce sustained remission and reduce corticosteroid reliance. FDA Approves Nipocalimab Generalized Myasthenia Gravis for Adults, Children Nipocalimab received FDA approval for gMG in antibody-positive patients aged ≥12, expanding therapeutic options across major serotypes. Semaglutide Improves Steatohepatitis, Fibrosis in Phase 3 MASH Trial Phase 3 trial results show semaglutide significantly improves steatohepatitis and fibrosis markers in patients with MASH, without worsening liver histology. Increased Fasting Blood Glucose Triples Risk of Heart Damage in Adolescents International data links elevated fasting glucose and insulin resistance in adolescence to markedly increased future risk of heart damage, especially among females.

Semaglutide 2.4 mg weekly led to significant resolution of MASH and reduction in fibrosis after 72 weeks

Commentary by Dr. Jijun Huang.

This week's expert, Hepatologist and Key Opinion Leader Scott Friedman, joins Roger to discuss advances in acceptance of gene therapy and knowledge in other areas of basic liver science. When discussing science, he pays particular attention to findings on the diversity of stellate cells and his interest in CAR-T as a therapy for liver disease.This conversation starts with Scott discussing gene therapy. Specifically, he applauds the idea that gene therapy is  becoming accepted in many diseases after a faulty start years ago, due to an unfortunate patient death in a badly controlled trial.  He comments that this acceptance has unique benefits in liver disease because the liver can regenerate so much faster and more efficiently than other organs. He mentions some of the rare liver diseases in which patients are benefiting from gene therapy, and notes that we now have gene therapies and early-stage trials to target PNPLA3 and  other genes associated with MASH and MASH cirrhosis. Next, Scott discusses stellate cells, which he has discussed in earlier episodes of SurfingMASH. Science is increasingly demonstrating how many different types of heterogeneous stellate cells exist. As Scott puts it, these cells "come in many flavors," each of which plays a different role in cell generation or cell death. In fact, the specific therapeutic challenges that present themselves may vary as a patient moves along the pathway from F1 to F2 to F3 to F4. Further, we are learning that there may be several different forms of MASH to present differently at a cellular level. This makes tremendous sense, given that no one drug has proven successful in even a significant majority of patients yet. As the conversation winds down, Scott shares what he describes as a "sobering note" about the state of research funding in America in 2025. As he notes, there are certain kinds of applied and developmental research that private companies do well, but other kinds of basic research that only occur when funded in public and not-for-profit sectors. As a specific example, he cites CRISPR, initially funded publicly and now in the hands of biotech companies, which is used to treat a variety of diseases more effectively than they could have been treated before, if at all. He also comments that a poor early commercial decision slowed the development of statins. 

This weekend's Newsmaker, Indiana University hepatologist and key opinion leader Naga Chalasani, joins Roger Green to discuss Early Experience with Resmetirom To Treat Metabolic-Associated Steatohepatitis with Fibrosis in a Real-World Setting, an article his group published recently in Hepatology Communications. He shares highlights from the paper and points out the one key area in which his group found room for improvement in their initial protocol. Naga and colleagues wrote this paper after learning from Madrigal Pharmaceuticals that they were among the largest early prescribers of resmetirom and, relative to others, had achieved reimbursement with virtually all their patients and a high percentage of patients actually starting the medication. After receiving requests from other states for advice, the group decided to author this paper.In the paper, Naga and colleagues focused on patient selection, care pathway, how IUHealth got the medicine to their patients, and experience with safety and tolerability.In the paper, Naga and colleagues discuss their experiences in prescribing resmetirom for 113 patients in the first seven months after resmetirom's approval. Of these, IUHealth succeeded in achieving reimbursement for 110 of them. Of these patients, 83 initiated therapy, and 16% of those discontinued. In this interview, Naga shares some of the decisions that made the group so successful in the first three areas and identifies one subsequent area where the group found an opportunity for improvement: systematic follow-up with patients after prescribing. He attributes the 16% discontinuation rate to a "prescribe and forget" policy, similar to one that was successful in HCV, where clinicians prescribed without systematic follow-up until blood levels were obtained three months later. With a "prescribe and follow up" policy that includes phone calls at 1 and 3 months, he anticipates discontinuation rates will fall to something akin to the 5% rate in Phase 3 trials. What makes this interview so fascinating is Naga's description of the thinking that went behind specific decisions the group made in terms of patient management and pathway and suggests other options that might work as well. In all, this interview provides an excellent guide for clinics and providers on how to best integrate resmetirom into their practices.

Hepatitis means inflammation of the liver. The liver is a vital organ that processes nutrients, filters the blood, and fights infections. When the liver is inflamed or damaged, its function can be affected. Heavy alcohol use, toxins, some medications, and certain medical conditions can cause hepatitis. However, hepatitis is often caused by a virus. In the United States, the most common types of viral hepatitis are hepatitis A, hepatitis B, and hepatitis C. ​Hepatitis D, also known as “delta hepatitis,” is a liver infection caused by the hepatitis D virus (HDV). Hepatitis D only occurs in people who are also infected with the hepatitis B virus. Hepatitis D is spread when blood or other body fluids from a person infected with the virus enters the body of someone who is not infected. Hepatitis D can be an acute, short-term infection or become a long-term, chronic infection. Hepatitis D can cause severe symptoms and serious illness that can lead to life-long liver damage and even death. People can become infected with both hepatitis B and hepatitis D viruses at the same time (known as “coinfection”) or get hepatitis D after first being infected with the hepatitis B virus (known as “superinfection”). There is no vaccine to prevent hepatitis D. However, prevention of hepatitis B with hepatitis B vaccine also protects against future hepatitis D infection. ​Hepatitis E is a liver infection caused by the hepatitis E virus (HEV). HEV is found in the stool of an infected person. It is spread when someone unknowingly ingests the virus – even in microscopic amounts. In developing countries, people most often get hepatitis E from drinking water contaminated by feces from people who are infected with the virus. In the United States and other developed countries where hepatitis E is not common, people have gotten sick with hepatitis E after eating raw or undercooked pork, venison, wild boar meat, or shellfish. In the past, most cases in developed countries involved people who have recently traveled to countries where hepatitis E is common. Symptoms of hepatitis E can include fatigue, poor appetite, stomach pain, nausea, and jaundice. However, many people with hepatitis E, especially young children, have no symptoms. Except for the rare occurrence of chronic hepatitis E in people with compromised immune systems, most people recover fully from the disease without any complications. No vaccine for hepatitis E is currently available in the United States. (credits CDC)

00:00:00 - Surf's Up: Season 6 Episode 5Host Roger Green briefly describes this episode's three sections and introduces Roundtable guests. The Roundtable panel shares groundbreakers. 00:10:39 - Roundtable: A Deep Dive Into Drug Development, Part OneThe opening portion of this month's roundtable centers around two issues: exciting data for FGF-21s and, more generally, treating patients with cirrhosis. Naim Alkhouri sets the tone in his opening comments, which start by focusing on the exciting SYMMETRY data from efruxifermin and then hones in on FGF-21s and resmetirom in cirrhosis. The rest of the conversation features Jörh Schattenberg, Sven Francque and Naim discussing therapies in development for compensated and decompensating cirrhosis.00;24:44 - Newsmaker: Naga Chalasani on Real-World Experience Prescribing ResmetiromNaga joins Roger to discuss the paper Early Experience with resmetirom to treat Metabolic Dysfunction-Associated Steatohepatitis With Fibrosis in a Real-World Setting from his group at Indiana University, which his group authored and Hepatology Communications recently posted. The paper, based on IU Health's experience with its first 113 resmetirom patients, shares the group's practical experience developing processes to work closely with the specialty pharmacies dispensing resmetirom and, finally, concludes that a more engaged patient management strategy might reduce drug discontinuation to a level comparable with clinical trials.  00:47:21 - Expert: Scott Friedman on Gene Therapy, Diversity of Stellate Cell Types, Other Basic Liver ScienceScott and Roger cover a range of basis science topics in a fast-moving 19-minute discussion. It starts with Scott discussing the increasing acceptance that gene therapy is an acceptable way to treat a range of liver diseases, many of which are orphan or ultra-orphan but, in fact, include potential gene therapies for non-cirrhotic MASH and MASH cirrhosis. He notes that in addition to classic gene therapy, which introduces protective gene variants into the systems of patients with the risky variants, gene therapy is now looking to introduce FGF-21 into patients through genetic modification. From there, the conversation covers CAR-T therapy, the increasing ability to identify many different types of stellate cells and the idea that the most effective therapy for eary fibrosis, advanced fibrosis and cirrhosis might require fundamentally different kinds of interventions. The two final elements are the idea that what we now call "MASH" may be several diseases with different etiologies with similar manifestations and a passionate call for all of us to support maintaining NIH funding in whatever ways we can.01:06:45 - Business ReportAs Roger copes with his laryngitis, AI voices deliver an abbreviated business report 

This week's newsmaker, Yukti Choudhury, Director of Clinical Development at HistoIndex, joins Roger Green to discuss FibroSIGHT, a new HistoIndex service that allows clinicians to use HistoIndex's Second Harmonic Generation (SHG) technology and analytics to determine specific CRN fibrosis level for patients with inconclusive NIT results.  One reason FibroSIGHT is worthy of attention: This is the first time an in-depth analysis of clinical trial biopsy results is being placed at the service of clinical treatment. Another reason: Yukti states that demand for this technique could equal 163,000 cases this year, rising to one million by 2028. The interview starts with Yukti sharing information on her own academic and commercial background and how she came to this role. She describes FibroSIGHT, a service that will provide a highly accurate CRN fibrosis level for patients whose NIT results suggest no clear or consistent finding. Yukti provides practical cues on ordering the test and its reimbursement. Roger shares his long-standing respect for SHG and the clarity it produces. He notes the economic benefit of determining whether a patient has F2 fibrosis, which is indicated for pharmacotherapy, vs.F1, which is not indicated. He sees clear benefit in this analysis. Roger goes on to express concern that any option requiring more biopsies will reduce the number of patients treated, particularly if having this tool encourages payers to require a biopsy as a prerequisite to treatment. He asks whether, over time, HistoIndex might be able to develop a companion analytic to improve these estimates without requiring biopsy. 

The timeline of diagnosis, to possible transplant recipient -- to post-transplant can feel like a whirlwind for patients and caregivers. Marion Marin, a lung transplant recipient, joins the show to discuss how that process went for her! She discusses advocating for yourself, waiting for 'the call' -- and the importance of the community around you when physically and emotionally dealing with a diagnosis! It's the 'Pulmonary Fibrosis' podcast! Brought to you the Wescoe Foundation for Pulmonary Fibrosis and the Pennsylvania IPF Support Network! Find this podcast wherever you get your podcasts! Are you interested in helping advance PF research? If so, consider joining a workgroup! Visit wescoe.org or pfpatientengagement.org for more details!See omnystudio.com/listener for privacy information.

Drs Carol H. Wysham and Scott Isaacs discuss incorporating the screening and management of metabolic dysfunction–associated steatotic liver disease in endocrine practice. Relevant disclosures can be found with the episode show notes on Medscape https://www.medscape.com/viewarticle/1002045. The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Type 2 Diabetes Mellitus https://emedicine.medscape.com/article/117853-overview Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): A State-of-the-Art Review https://pubmed.ncbi.nlm.nih.gov/37700494/ Fibrosis-4 (FIB-4) Calculator https://www.hepatitisc.uw.edu/page/clinical-calculators/fib-4 Liver Fibrosis Assessment: MR and US Elastography https://pubmed.ncbi.nlm.nih.gov/34687329/ Using the FIB-4, Automatically Calculated, Followed by the ELF Test in Second Line to Screen Primary Care Patients for Liver Disease https://pubmed.ncbi.nlm.nih.gov/38806580/ American Association of Clinical Endocrinology Clinical Practice Guideline for the Diagnosis and Management of Nonalcoholic Fatty Liver Disease in Primary Care and Endocrinology Clinical Settings: Co-Sponsored by the American Association for the Study of Liver Diseases (AASLD) https://pubmed.ncbi.nlm.nih.gov/35569886/ Mediterranean Diet and Nonalcoholic Fatty Liver Disease https://pubmed.ncbi.nlm.nih.gov/29785077/ Drug Treatment for Metabolic Dysfunction-Associated Steatotic Liver Disease: Progress and Direction https://pubmed.ncbi.nlm.nih.gov/39470028/ Current Status of Glucagon-Like Peptide-1 Receptor Agonists in Metabolic Dysfunction-Associated Steatotic Liver Disease: A Clinical Perspective https://pubmed.ncbi.nlm.nih.gov/39801787/ Sodium-Glucose Transport Protein 2 (SGLT2) Inhibitors https://www.ncbi.nlm.nih.gov/books/NBK576405/ Update on the Applications and Limitations of Alpha-Fetoprotein for Hepatocellular Carcinoma https://pubmed.ncbi.nlm.nih.gov/35110946/

Read the article here: https://journals.sagepub.com/doi/full/10.1177/30494826241296412

The EVOLVED trial investigated whether early aortic valve intervention could improve outcomes in asymptomatic patients with severe aortic stenosis and myocardial fibrosis. The randomized, multicenter study of 224 patients found no significant difference in all-cause mortality or unplanned aortic stenosis-related hospitalizations between early intervention and guideline-directed conservative management. However, early intervention was associated with lower rates of NYHA class II-IV symptoms and fewer unplanned hospitalizations. The trial highlights the potential symptomatic benefits of early intervention but underscores the need for further research to assess long-term outcomes.

Good morning from Pharma and Biotech daily: the podcast that gives you only what's important to hear in Pharma and Biotech world. Bristol Myers Squibb is seeking to broaden the use of its CAR T cell therapy, Breyanzi, to address marginal zone lymphoma as a strategy to offset losses from exclusivity. In other news, Boehringer Ingelheim has seen promising results in a Phase III trial for its lung fibrosis drug, randomilast, aimed at progressive pulmonary fibrosis. However, Pliant has experienced a stock decline following the halt of its Phase IIb/III study for idiopathic pulmonary fibrosis. Additionally, Vertex has received FDA approval for its non-opioid pain treatment, while AbbVie has secured approval for a new antibiotic. Bain's acquisition of Tanabe for $3.3 billion is also making headlines. Regeneron is currently in a legal battle with Sanofi over the Dupixent pact, and Equillium's itolizumab is undergoing testing against Humira for ulcerative colitis. On the horizon, Acelyrin and Alumis are joining forces to address immune-mediated diseases, while Eisai is seeking subq approval for Leqembi due to sluggish US sales. Job opportunities are available at ATCC, AbbVie, Regeneron Pharmaceuticals, and Dren Bio.

Interview with Katherine A. Hutcheson, PhD, author of Manual Therapy for Fibrosis-Related Late Effect Dysphagia in Head and Neck Cancer Survivors: The MANTLE Nonrandomized Clinical Trial. Hosted by Paul C. Bryson, MD, MBA. Related Content: Manual Therapy for Fibrosis-Related Late Effect Dysphagia in Head and Neck Cancer Survivors

Interview with Katherine A. Hutcheson, PhD, author of Manual Therapy for Fibrosis-Related Late Effect Dysphagia in Head and Neck Cancer Survivors: The MANTLE Nonrandomized Clinical Trial. Hosted by Paul C. Bryson, MD, MBA. Related Content: Manual Therapy for Fibrosis-Related Late Effect Dysphagia in Head and Neck Cancer Survivors

EVOLVED: Early Intervention in Patients with Asymptomatic Severe Aortic Stenosis and Left Ventricular Myocardial Fibrosis

In this episode, Naim Alkhouri, Mike Betel, Michelle Long and Jeff McIntyre join Jörn Schattenberg and Roger Green to look back at The Liver Meeting 2024. This conversation reviews the ESSENCE trial, the Phase 3 trial demonstrating that semaglutide regresses fibrosis levels in some MASH patients.  The conversation begins with each panelist sharing a word or short phrase they felt best captured their feelings about TLM2024. Next, panelists review the meeting's most consequential paper, the ESSENCE Trial. Naim starts by describing ESSENCE, a Phase 3 trial with semaglutide demonstrating significant levels of fibrosis regression in non-cirrhotic MASH patients. Jörn adds the hopeful note that NITs performed as well as or better than biopsy in this trial, which he hopes will speed the transition in diagnostic approaches and tools. Jeff and Mike agree that from the patient's perspective, ESSENCE will be seen as a milestone in MASH therapy: the proof that a second drug can succeed in MASH. As the conversation ends, Roger notes that approval of a second agent for a particular disease often leads to dramatic growth in overall drug treatment by changing the pivotal question from whether to treat with a drug to which choice to prescribe. 

In this episode, Naim Alkhouri, Mike Betel, Michelle Long and Jeff McIntyre join Jörn Schattenberg and Roger Green to look back at The Liver Meeting 2024. This conversation reviews the late-breaker presentation on efimosermin, a q4w FGF-21 agent and the "FDA Corner" session. Jörn begins the discussion by highlighting a paper from the later breaker session on efimosfermin alfa, an FGF-21 agent dosed q4w. He notes that after only six doses (24 weeks), efimosfermin alfa demonstrated significant increases in fibrosis regression and lowering NAS score. To Jörn, this result, coupled with others on efruxifermin and pegozafermin, suggest that FGF-21s are likely to play a significant role in MASH therapy once approved. After Roger and Mike note their enthusiasm about the drug class and this study, Jörn mentions a study with 96-week efruxifermin that data demonstrates prolonged efficacy. As he points out, this matters because while studies of an earlier FGF-21 candidate suggested that antibodies might develop in FGF-21 therapy, that does not appear to be an issue here. Mike asks the group why they feel placebo performs so well in clinical trials. Jörn suggests that working with a compassionate clinical care team in dealing with the patient leads to better performance on diet and exercise and, as a result, increased placebo response to what we might find in general community practice.Michelle praises the FDA Corner session, particularly the agency's transparency and willingness to engage industry and academia in finding paths to move away from biopsy. She also notes some of the practical challenges inherent of moving away from biopsy using data from earlier trials with an outmoded histology reader setup. She is optimistic about the scientific community coming together to address these issues. Jeff praises the agency for an "amazing" session. 

rWotD Episode 2792: Myocardial scarring Welcome to Random Wiki of the Day, your journey through Wikipedia’s vast and varied content, one random article at a time.The random article for Wednesday, 25 December 2024 is Myocardial scarring.Myocardial scarring is the accumulation of fibrous tissue resulting after some form of trauma to the cardiac tissue. Fibrosis is the formation of excess tissue in replacement of necrotic or extensively damaged tissue. Fibrosis in the heart is often hard to detect because fibromas, scar tissue or small tumors formed in one cell line, are often formed. Because they are so small, they can be hard to detect by methods such as magnetic resonance imaging. A cell line is a path of fibrosis that follow only a line of cells.This recording reflects the Wikipedia text as of 00:45 UTC on Wednesday, 25 December 2024.For the full current version of the article, see Myocardial scarring on Wikipedia.This podcast uses content from Wikipedia under the Creative Commons Attribution-ShareAlike License.Visit our archives at wikioftheday.com and subscribe to stay updated on new episodes.Follow us on Mastodon at @wikioftheday@masto.ai.Also check out Curmudgeon's Corner, a current events podcast.Until next time, I'm generative Amy.

This week we delve into the world of adult congenital heart disease to review the topic of liver disease in the Fontan patient and specifically, hepatocellular carcinoma (HCC). What is the prevalence of this disease in the Fontan single ventricle adult patient? How effective are scores like the MELD-XI or Fibrosis-4 Index at identification of HCC in the Fontan patient? How should the Fontan adult patient be surveilled for this form of cancer? What evidence is there that earlier identification of HCC is associated with better outcomes? What may prove to be the most important factor in protection of the liver in the Fontan patient? Dr. Yuli Kim, Director of the ACHD program at The University of Pennsylvania shares her deep insights this week into this important topic. DOI: 10.1093/eurheartj/ehad788

Lynette Chambers, a 9-year PAH (pulmonary arterial hypertension) patient, has also been diagnosed with pulmonary fibrosis (PF). She shares her journey, from struggling with daily activities to being admitted to the hospital with severely low oxygen levels. Lynette discusses the emotional challenges of facing a terminal illness and the difficulty of balancing work and family time. Despite the hard reality, Lynette emphasizes the importance of gratitude, making others feel better, and being the best version of oneself. She finds strength in her family, especially her grandchildren, and strives to create lasting memories and make a positive impact on those around her. Learn more about pulmonary hypertension trials at www.phaware.global/clinicaltrials. Engage for a cure: www.phaware.global/donate #phaware Share your story: info@phaware.com Like, Subscribe and Follow us: www.phawarepodcast.com. @phacanada

Silicosis is a lung disease caused by inhaling tiny crystalline particles of silica, or silicon dioxide, often linked to work environments like mining, construction, stonework, and sandblasting. The disease leads to symptoms such as coughing, inflammation, and fibrosis (scarring) and is classified under pneumoconioses, a group of lung conditions caused by inhaling dust. Silicosis can be chronic, developing over more than 10 years of exposure; subacute, occurring in two to five years with heavier exposure; or acute, which can happen within months of intense exposure. Although silicosis is irreversible and has no cure, treatments are available to manage symptoms.

In this week's episode we'll discuss how immune fitness impacts response to teclistamab in relapsed/refractory multiple myeloma; learn more about a new mechanism of resistance to asciminib conferred by the BCR::ABL1 M244V mutation, and discuss the impact of hematopoietic cell transplantation on myocardial fibrosis in young patients with sickle cell disease. Featured Articles:Correlation of immune fitness with response to teclistamab in relapsed/refractory multiple myeloma in MajesTEC-1BCR::ABL1 kinase N-lobe mutants confer moderate to high degrees of resistance to asciminibImpact of hematopoietic cell transplantation on myocardial fibrosis in young patients with sickle cell disease

In the second half of Roger Green's interview with Global Liver Institute Vice President, Liver Programs Jeff McIntyre, Jeff discusses the implications of his key EASL Congress takeaways for GLI and other patient advocacy groups.  To Jeff, this trend makes patient advocates a more valuable player in the clinical trial design process, particularly when coupled with the FDA's increasing focus on diversity in trial populations. This will become particularly important because, today, the major use of incretin agonists like semaglutide and tirzepatide is in anti-obesity, where payers are frequently declining to pay for the drugs. Advocates like GLI will be pivotal in ensuring that patients who need MASLD drugs will still get the drugs they need, particularly at earlier stages of fibrosis. This discrimination may allow patients to receive incretin agonists during the pre-fibrosis stage based on diabetes and anti-obesity medications and reserve the fibrosis drugs for patients with more advanced MASH. The entire scenario of early metabolic, later MASH treatment with different agents is at least 4-5 years in the future. In the meantime, Jeff sees a need to advocate for underserved groups in the population while at the same time laying the foundation for the longer-term case. In this context, the United Nations General Assembly side effect (covered in S5, E22) is an exciting and vital event.

This conversation contains the first half of Roger Green's interview with PharmaNest Founder and CEO Mathieu Petitjean. After Matt tells the audience a little about his background and PhramaNest, the two discuss what Matt considered the key strategic takeaways for PharmaNest from the various EASL Congress presentations, abstracts and discussions. Before answering the question, Matt describes the core services his company offers: "PharmaNest specializes in digital pathology. Four years ago, we put down the hypothesis that the histological phenotype of fibrosis should be quantified in a high-resolution, sophisticated way." He goes on to state their core proposition for MASLD: "The big idea here is that fibrosis equals phenotype." He proceeds to describe his offerings in greater detail before offering the underlying value of computed histology: fibrosis is a continuous variable that is scored in discrete categories under the NASH-CRN model that drives FDA analysis. With this as context, he answers the question by describing three kinds of MASLD clinical trial designs. The first, earliest trials had a single pathologist reading histological slides. The method is not precise, but the drugs were not very good, and none were ultimately approved. The second set of trials relied on more rigorous methods for pathologists to read histology slides, with multiple readers and robust adjudication systems. Also, the drugs in this second set of trials were more efficacious, so that NASH-CRN, while a blunt instrument, could adequately assess efficacy. For the third set of trials, Matt believes non-invasive tests (NITs) are likely to suffice.

In the second half of Roger Green's interview with PharmaNest Founder and CEO Mathieu Petitjean, Matt discusses the implications of his key EASL Congress takeaways for PharmaNest.  Matt starts this discussion with a simple question: Will biopsy-based analyses become part of a surrogate endpoint? As he points out, they are not today, and creating the necessary data might require a significant effort. If not, they are unlikely to remain relevant to the large, Phase 3 trials. Regardless of the answer to this question, Matt believes digital pathology will still be important in pre-clinical work and other efforts to define underlying liver structures and faults better. Also, he notes, digital pathology is valuable in an array of other liver diseases and in non-hepatological markets, notably including pathology. One way or another, he is confident PharmaNest will continue to make contributions to hepatology and grow as a business.

00:00:00 - Surf's Up: Season 5 Episode 24 This week's episode on MASLD lessons from the EASL Congress 2024 includes three separate elements: individual interviews with PharmaNext Founder and CEO Mathieu Petitjean and Global Liver Institute Vice President of Liver Programs Jeff McIntyre,  followed by a discussion with patient advocates Mike Betel of the Fatty Liver Alliance and José Willemse from the Netherlands, now supporting EASL. 00:02:45 - IntroductionRoger explains the episode format, including the two key questions for Mathieu and Jeff: (i) what were their key takeaways from the EASL Congress, and (ii) how have those takeaways changed how they do their jobs or plan for the future? Roger also sets up the Question of the Week discussion that is today's third section. 00:04:04 - Meet Mathieu PetitjeanThis is the SurfingMASH debut for Mathieu Petitjean, Founder and CEO of PharmaNest. He tells the audience a bit about his background and his love of Harleys.00:07:10 - First question to MattMatt begins by describing the core services Pharmest, a digital pathology company, offers MASH drug developers. Then he answers Roger's question by describing three phases in MASLD clinical trial designs. His point is that over time, drugs have gotten better, and histology requirements have become more onerous. At some point in the not-too-distant future, Matt believes non-invasive tests (NITs) are likely to suffice in large Phase 3 trials of the future.00:21:01 - Second question to MattMatt starts the answer with a conditional: if biopsy-based analyses become part of a surrogate endpoint, the role is large and clear. If not, they are unlikely to remain relevant in Phase 3 trials. Regardless of the answer to this question, Matt believes digital pathology will remain important in pre-clinical work and in other continuous liver diseases with less-defined targets. Also, he says, digital pathology is valuable in an array of non-hepatological markets, notably including pathology. 00:29:11 - First question to JeffJeff describes an "overriding sense of optimism" he felt due to the many positive drug trials presented in Milano. This suggests that the MASLD community is developing safe and effective MASH drugs with many different modes of action. This is allowing GLI and other advocates to start to have "more enlightened discussions" about MASLD in the context of the patient's overall metabolic state. All this means that what works in one patient might not in another. This can reshape clinical trials so that the endpoint target might not be change in fibrosis but impact against specific NIT targets. Jeff envisions this line of inquiry as a possible step away from biopsy. 00:39:34 - Second question to JeffConcurrently, FDA is beginning to require greater diversity in clinical trial populations. To Jeff, all this makes patient advocates like GLI more valuable to the clinical trial design process and pivotal in ensuring that metabolic and advanced MASH patients will still get the drugs they need. Starting today, Jeff sees advocates as championing underserved groups in the population while at the same time laying the foundation for the longer-term case. 00:55:20 - Discussing previous "Question of the Week"This is a 15-minute discussion of the Question of the Week we posed at the end of S5 E23. This section will constitute S5 E24.5, which we will post in the next day or two. A more complete summary will appear there. 01:11:23 - Question of the WeekThe Question of the Week is the first question Roger asks Matt and Jeff during this episode.01:12:58 - Business ReportPreviewing Episode 25, with Maru Rinella discussing the recently-published expert recommendations on use of resmetirom, along with comments on office hours the reason we will not have a vault conversation this week.

Episode 172: NAFLD and ObesityFuture Dr. Nguyen explains the pathophysiology of non-alcoholic fatty liver disease and how it relates to obesity. Dr. Arreaza gives information about screening and diagnosis of NAFLD. Written by Ryan Nguyen, MS4, Ross University School of Medicine. Comments by Hector Arreaza, MD.You are listening to Rio Bravo qWeek Podcast, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California, a UCLA-affiliated program sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home. This podcast was created for educational purposes only. Visit your primary care provider for additional medical advice.Introduction/PathophysiologyNonalcoholic fatty liver disease (NAFLD) refers to the buildup of excess fat in liver cells, occurring without the influence of alcohol or drugs. Nonalcoholic steatohepatitis (NASH) represents a more severe form of NAFLD, characterized by inflammation and liver cell injury due to fat accumulation. If left untreated, NASH can progress to liver fibrosis or cirrhosis. Typically, NAFLD/NASH is diagnosed after other liver conditions are ruled out, making it a diagnosis of exclusion.NAFLD -> NASH -> Cirrhosis -> Liver failure. Another term for NAFLD is metabolic dysfunction-associated steatotic liver disease. Fatty liver disease is identified when more than 5% of liver weight consists of fat, whereas, NASH is diagnosed when this fat accumulation is accompanied by inflammation and liver cell injury, sometimes leading to fibrosis. Understanding these distinctions is crucial in recognizing and managing the spectrum of liver conditions associated with obesity and metabolic syndrome.BMI serves as a tool to gauge body fat levels: individuals are categorized as normal weight if their BMI falls between 18.5 and 24.9, overweight if it ranges from 25 to 29.9. Class I obesity is diagnosed with a BMI of 30 to 34.9, class II obesity between 35 and 39.9, and class III obesity when BMI exceeds 40.Obesity puts you at risk of NAFLD, but you can also see NAFLD in non-obese patients, but the prevalence is very low, about 5%. What did you learn about the demographics of NAFLD?NAFLD is most widespread in regions like South Asia, the Middle East, Mexico, Central and South America, with prevalence rates exceeding 30%. In the United States, prevalence varies with approximately 23-27%, notably higher among Asians at 30%, followed by Hispanic individuals at 21%, White individuals at 12.5%, and Black individuals at 11.6%. Across all racial groups, obesity plays a significant role, affecting more than two-thirds of individuals diagnosed with NAFLD. Understanding these demographics underscores the global impact of obesity on NAFLD prevalence.Diagnosis: Screening/Labs/Imaging/ToolsThe American Association for the Study of Liver Diseases does not recommend screening for NAFLD, but if it is discovered an appropriate workup is warranted. AST/ALT RatioLiver health can be assessed by a series of tests aimed at assessing fat accumulation, inflammation, and fibrosis. Initial screening often includes laboratory tests such as measuring the ratio between aspartate transaminase (AST) and alanine transaminase (ALT), where a ratio less than 1 may suggest possible NAFLD, although it is not diagnostic on its own. Normally, AST is slightly more elevated than ALT. So, if the AST/ALT ratio is lower, then means that ALT is higher than AST. FibroSure®.Additionally, you can measure indirect markers of fibrosis with tests such as FibroSure or FibroTest blood tests that combine several biomarkers including age, sex, gamma-glutamyl-transferase (GGT), total bilirubin, alpha-2-macroglobulin, apolipoprotein A1, haptoglobin, and ALT to provide insights into liver health.Some people may be more familiar with FibroSure before Hepatitis C treatment. You can get a fibrosis score (F0-F4), and it is considered significant fibrosis if the score is > or equal to F2. Imaging plays a crucial role in diagnosing NAFLD without the need for invasive procedures like liver biopsy. Vibration-controlled transient elastography (Fibroscan) uses ultrasound to measure liver stiffness, indicating potential fibrosis and inflammation. While noninvasive and portable, it focuses solely on liver ultrasound and may not be universally accessible. MRI with proton density fat fraction (MRI-PDFF) offers a comprehensive assessment of liver fat content, commonly used in clinical and research settings for NAFLD and NASH evaluation.For evaluating hepatic fibrosis in patients with suspected NAFLD, tools like the Fibrosis-4 Index (FIB-4) incorporate age, AST, ALT, and platelet count to estimate the likelihood of liver disease progression. These screening methods collectively aid in diagnosing and monitoring NAFLD, particularly in individuals at risk due to factors like prediabetes, type 2 diabetes, obesity, and abnormal liver enzyme ratios. With the FIB-4 you can get a faster answer than FibroSure because you only need 4 elements: Age, platelet count, AST and ALT. Cirrhosis is less likely if FIB-4 is 3.25. Understanding these diagnostic approaches is essential for early detection and management of NAFLD in clinical practice.Some researchers are invested in diagnosis and treating NAFLD while others recommend against labeling patients with NAFLD. A 2018 Lancet article concluded that the risks of over-diagnosing and overtreating NAFLD exceed the benefits of screening or periodic imaging because of “the low hepatic mortality, high false-positive rate of ultrasonography, selection bias of current studies, and lack of viable treatment.” However, patients who suffer from metabolic syndrome should be counseled about dietary modification and physical activity regardless of their liver condition. NAFLD and obesityFatty liver disease is often caused by multiple insults towards either genetically or environmentally predisposed individuals. Family history of NAFLD and having specific genetic variants are important risk factors for NAFLD. Those with prior health conditions can have increased susceptibility to NAFLD including T2DM leading to insulin resistance, metabolic syndrome, sleep apnea, hepatitis C, and cardiovascular or chronic kidney disease. A sedentary lifestyle and unhealthy nutrition (especially high intake of processed carbohydrates) cause an increase in free fatty acids leading to hepatic fat deposition → ballooning of hepatocytes → leading to hepatocyte injury/death → inflammation with fibroblast recruitment → end result of fibrosis/cirrhosis. Just a quick reminder, NAFLD is defined as fatty liver with >5% hepatic fat and NASH is defined as fatty liver with >5% hepatic fat with inflammation, hepatocyte injury, with or without fibrosis that we can determine through imaging. A leading concern for the development of NAFLD is the consumption of high fructose corn syrup.  High fructose corn syrup (HFCS), commonly found in candy, processed sweets, soda, fruit juices, and other processed foods, is linked to non-alcoholic fatty liver disease (NAFLD). Unlike natural whole fruits, which contain fiber and are generally healthier due to their slower absorption, HFCS lacks fiber and is quickly absorbed, leading to rapid transport to the liver. This process contributes to NAFLD by increasing the hepatic synthesis of lipids and interfering with insulin signaling. To avoid HFCS, individuals are encouraged to consume whole fruits rather than fruit juices and adopt diets rich in whole grains, lean meats, plant-based proteins, fruits, and vegetables, such as the Mediterranean or DASH diets, which are less likely to promote NAFLD, especially in those with healthy body weight.NAFLD treatment.Avoiding alcohol seems very obvious, but we need to mention it. Avoiding heavy alcohol consumption is recommended and complete abstinence is suggested.Weight loss is crucial; even a modest reduction of 3–5% in body weight can alleviate hepatic steatosis, with greater improvements typically seen with 7–10% weight loss, particularly beneficial for addressing histopathological features of NASH, such as fibrosis. We must focus on tailored medical nutrition therapy and regular physical activity. A strategic meal plan is essential, emphasizing achieving a healthy body weight while limiting trans fats and ultra-processed carbohydrates. Options like the Mediterranean diet, which balances lean proteins and restricts processed carbohydrates have shown promise. Dynamic aerobic and resistance exercises play a significant role in managing NAFLD. They help maintain a healthy weight and enhance peripheral insulin sensitivity, reduce circulating free fatty acids and glucose levels, and boost intrahepatic fatty acid oxidation while curbing fatty acid synthesis. These benefits contribute to mitigating liver damage associated with NAFLD, offering therapeutic advantages beyond mere weight reduction.Exercise may not be a great tool for weight loss, but it is a great tool for weight maintenance, liver health, and overall health as well. “Most patients with NAFLD die from vascular causes, but NAFLD puts patients at increased risk of cardiovascular death”. Medications for NAFLD.Regarding pharmacotherapy, while no medications are currently FDA-approved specifically for NAFLD treatment, some options show promise in clinical settings. Vitamin E supplementation at 800 IU (international units) daily has demonstrated biochemical and histological improvements in NASH cases without diabetes or cirrhosis, though long-term use may elevate prostate cancer risks. It is important to make a shared decision with the patient before starting Vitamin E supplementation. Medications like pioglitazone can reduce liver fat and improve NASH, even as they may increase body weight. But our favorite, GLP-1 receptor agonists, such as liraglutide and semaglutide, also show potential in reducing liver fat and improving NASH symptoms, and this is an emerging therapeutic option for managing this condition.If you decide to treat, then you should monitor as part of the treatment. An aminotransferase check is recommended 6 months after starting a weight loss program. If levels do not improve or do not return to normal after 5-7% of weight loss, another cause of elevated transaminases needs to be investigated.You also need to monitor fibrosis in patients with >F2. If fibrosis has been proven by liver biopsy, you can order FibroSure every 3-4 years. Having a fatty liver may be a red flag that your patient has a metabolic problem. If you discover it, start interventions that would benefit not only the liver but the whole metabolic profile of your patient. The Obesity Medicine Association (OMA) issued a Clinical Practice Statement (CPS) regarding NAFLD and obesity stating that patients with obesity are at increased risk for NAFLD and NASH. It recommends that clinicians strive to understand the etiology, diagnosis, and optimal treatment of NAFLD with a goal to prevent NASH in their patients.Regular exercise, even walking 30 minutes a day can show many benefits in curbing fatty accumulation in the liver. Having a proper diet with avoidance of high fructose corn syrup can overall help in reducing NAFLD/NASH. _____________________Conclusion: Now we conclude episode number 172, “NAFLD and Obesity.” Future Dr. Nguyen explained that NAFLD and obesity are closely related and NAFLD can lead to NASH and cirrhosis in some patients. Dr. Arreaza explained that screening may not be recommended by some medical societies, but others are in favor of screening and treating this disease. However, most people agree that NAFLD is a sign of metabolic disease and a good reason to talk about healthy eating and physical activity with our patients. There are no FDA-approved medications to treat NAFLD, but some evidence suggests that Vitamin E can improve it and GLP-1 receptor agonists are a promising option. This week we thank Hector Arreaza and Ryan Nguyen. Audio editing by Adrianne Silva.Even without trying, every night you go to bed a little wiser. Thanks for listening to Rio Bravo qWeek Podcast. We want to hear from you, send us an email at RioBravoqWeek@clinicasierravista.org, or visit our website riobravofmrp.org/qweek. See you next week! _____________________References:Karjoo S, Auriemma A, Fraker T, Edward H. Nonalcoholic fatty liver disease and obesity: An Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) 2022. https://doi.org/10.1016/j.obpill.2022.100027.Curry M, Afdhal N. Noninvasive assessment of hepatic fibrosis: Overview of serologic tests and imaging examinations.  https://www.uptodate.com/contents/noninvasive-assessment-of-hepatic-fibrosis-overview-of-serologic-tests-and-imaging-examinationsRoyalty-free music used for this episode: Cool Groove (Alt-Mix) by Videvo, downloaded on Nov 06, 2023, from https://www.videvo.net

00:00:00 - Surf's Up: Season 5 Episode 21 One important session at the EASL Congress 2024 involved the presentation of the new MASLD Clinical Practice Guidelines. CPG co-authors Elisabetta Bugianesi and Frank Tacke join Louise Campbell and Roger Green to share their perspectives on the guidelines' development some key recommendations.  00:09:36 - Revising the guidelines Roger asks the co-authors to describe the process that led to the 2021 decision to revise the guidelines. EASL was the initial driver; EASD and EASO joined the process. They formed a committee of 15 leaders and assembled a Delphi panel of 46 individuals from different stakeholder communities.  Elisabetta describes the "big advantage" of this collaboration: it conveyed the need for a common way to manage co-morbid patients with MASLD. To Frank, this approach strengthened the guidelines by putting the liver in the center of metabolic disease. Louise asks whether the guidelines will increase the profile of liver disease in other specialties. Elisabetta says "it takes time" but says that the nature of cirrhosis and HCC might make this easier.00:19:07 - Adding resmetirom before approvalEarlier, Louise praised the inclusion of resmetirom in the guidelines, Frank notes that this section was added to the guidelines within a month before their release and praises the "very engaged Delphi panel" that reacted and voted quickly.  He proceeds to discuss how the Delphi panel was formed.00:23:24 - Major issues in screening, diagnosing and case-managing patientsElisabetta starts by saying that resmetirom's approval created momentum for screening. She says the approach identifies patients before cirrhosis or HCC in pre-cirrhotic patients. Frank points out "a major breakthrough": these guidelines do not rely on biopsy.  00:28:04 - Non-medical factors Louise lauds the document's the broad range of diets that will make the document valuable around the world . Frank adds that the guidelines have adjusted thresholds  adapted to the ethnic and socioeconomic background of the individual. 00:30:52 - Pharmacological issues in the new CPG Frank starts the pharmacological discussion noting that the CPG drives holistic thinking about the liver in a metabolic context. Elisabetta notes that while no drugs are efficacious for cirrhosis, the document does report that some drugs are safe for these patients, although sometimes with adjusted doses. 00:33:39 - Screening for cirrhosisFrank concurs that the document provides guidance on managing patients with end-stage liver disease and also discusses how to manage cirrhosis and its various complications. Elisabetta says that HCC can be hard to find in a fatty liver. 00:36:36 - Cardiometabolic nursing as a future training and specialtyLouise suggests that these guidelines "pinpoint...a role of the potential future" for nurses who can support the entire cardiometabolic syndrome. This document might drive a curriculum for such a specialization.00:38:48 - What adjustments would you like to see in the healthcare system?The last set of questions begins with Roger asking what kinds of changes the authors would like to see in the healthcare system.  The discussion revolves around a "cardiometabolic" perspective but in terms of nurse training and the care provided in a hepatologist's office. 00:43:18 - Winding downAs the conversation winds down, each panelist offers a final comment or question.00:47:59 - Question of the WeekRoger asks how readily listeners believe the guidelines will be implemented, and which sections will be easiest and hardest to implement. 00:48:32 - Business ReportThe next EASL Congress review episodes, starting office hours, and a vault discussion from 2023's clinical care pathway document. 

In this conversation from July 2023, Stephen Harrison, Jörn Schattenberg and Roger Green discuss the implications of presentations on the FGF-21 agent efruxifermin and the dual GLP/glucagon agonists pemvidutide and efinopegdutide. Here is the description Roger wrote for the original conversation:In this session, conversation shifts from resmetirom to Mazen Noureddin's "NASH Monopoly" game and focuses on the value of FGF-21s and glucagon agents. Stephen posits two comments about GLP-1s. First, there is now adequate data suggesting that GLP-1s will not melt away all liver fat and as a result lead to dramatic fibrosis regression. Second, we know from a small sub-cohort of patients in Akero's SYMMETRY trial that patients already on fairly low doses of GLP-1s saw what Stephen describes as an 'incredible' and incremental benefit for the FGF-21 agent, efruxifermin. The group notes that while glucagon dual and treble agents are likely to produce dramatically more robust results in weight loss and liver defatting than GLP-1s alone, they still seem unlikely to 'usurp the need for other types of agents.' From here discussion considers the FGF-21 class. Stephen notes that two drugs, efruxifermin and pegozafermin, have demonstrated significant efficacy against fibrosis. As the conversation concludes, the panelists agree that earlier, more aggressive screening to arrest cirrhosis will become pivotal and will not occur until the right drug becomes available. 

Mazen Noureddin and Naim Alkhouri join Jörn Schattenberg and Roger Green to discuss some of the other major drug development stories from the EASL Congress 2024, with special focus on denifenstat, ION-224 and TAK-227, and to review the SPECIAL study on bariatric surgery and cirrhosis. The panelists concur that all three of these agents have potential value in therapy. Naim expresses some concern about how broad denifestat use will be based on its side effect profile. Later in this conversation, Mazen belives that denifenstat has broad potential for use, given that the most prominent side effect, hair thinning, appears transient and readily manageable. He also notes that denifenstat's impressive results were based on Intent to Treat analysis, which is more rigorous.  Naim states his interest in the ION-224 agent based on its mode of action, which is RNA interference. He also discusses SPECIAL, a study he conducted with the bariatric surgery group at Cleveland Clinic. This study, which evaluated patients with cirrhosis at the time of surgery, demonstrated a 72% risk reduction in major adverse liver outcomes over a 10-year period and 80% risk reduction in decompensation. Jörn discusses a study he presented on TAK-227, a TG2 inhibitor originally developed for celiac disease. Early results here are quite promising and, as Aleksander Krag mentioned in S5 E17, demonstrates exciting potential for collaboration with drug developers for other diseases. As the conversation ends, Roger asks Mazen and Jörn what they consider likely to be the biggest MASLD stories at the AASLD Liver Congress in November. Mazen selects the Phase 3 ESSENCE study for semaglutide, while Jörn suggests NITs. 

Mazen Noureddin and Naim Alkhouri join Jörn Schattenberg and Roger Green to focus on the role FGF-21s will play in long-term advanced fibrosis treatment: induction or long-term therapy...or might we even think of the class as being able to produce a "MASH cure?" Responding to Naim's comment closing the previous discussion, Mazen questions why we regard FGF-21 agents as induction therapies given that it appears to be as well tolerated as the oral agents and maintains such efficacy over time. In fact, he adds, its sustained efficacy might make it possible for livers to eliminate fibrosis and return to their "normal" state, almost like a "cure." Jörn adds a comment about pegozafermin, another FGF-21 in development. Jörn notes that this agent is a pegylated molecule, which makes it different from efruxifermin. He notes that NITs show sustained enzyme response at 48 weeks. Mazen reiterates his optimism about the FGF-21 class and reminds us that there is a third FGF-21 in development. Roger raises Michael Charlton's question (Season 5 Episode 11) whether an induction therapy strategy for FGF-21s might not work if removing the drug allows the MAS activity to return. On the other hand, he notes, it might take years for fibrosis to return. Mazen agrees that many unanswered questions exist, but reiterates his belief in long-term therapeutic value.  

Mazen Noureddin and Naim Alkhouri join Jörn Schattenberg and Roger Green to discuss the tirzepatide late-breaker at the EASL Congress 2024 and other "Twin-cretins," all of which are GLP-glucagon combinations. "Twin-cretins" is the name Jörn has coined for agents with a GLP-1 agonist plus another incretin effect. Tirzepatide is a GLP/GIP agent, while survodutide and the agents discussed last year, pemvidutide and efinopegdutide, are GLP/gluagons. Naim reviews the results of the tirzepatide late-breaker presentation. As expected, it showed high rates of MASH resolution. Naim does not feel it answered the question whether an incretin-agonist can achieve significant fibrosis regression without a direct liver effect, since it relied on a completer analysis that treated 3 of 10 non-completers as a success (in ITT, that would have been 0 out of 10). Again, glucagon has a direct effect; GIP does not.This takes Naim back to the question of whether a GLP/GOP can have a meaningful effect on fibrosis. He notes that Stephen believed firmly that it could not, but there is a paradox in that bariatric surgery can produce a reduction in fibrosis. Naim notes that conclusive data will arrive later this year, so no one needs to decide now. Mazen praises tirzepatide's effect on weight loss and safety and could prescribe it now, but the completer analysis has not persuaded him to prescribe to regress fibrosis, particularly given the lack of a dose response. He notes that "while I don't want to compare apples to oranges," he is more confident in the glucagon effect found with survodutide, pemvidutide and efinopegdutide. Jörn agrees. Roger asks how prescribing decisions will change in a market where a significant share of US patients will have been prescribed semaglutide or tirzepatide before coming to the hepatologist. Naim comments that many of his MASH patients have been on GLP-1 already.  He notes that since glucagon increases blood sugar, the ratio of GLP-1:glucagon is a key issue and difference between the three GLP/glucagon agents. 

Naim Alkhouri and Mazen Noureddin join Jörn Schattenberg and Roger Green to discuss issues regarding incretin agonists and results from the efruxiermin late-breaker at the EASL Congress 2024. Naim shares his general excitement about glucagon agents in general. He mentions that the efinopegdutide study included a semaglutide cell, which showed further reduction in liver fat vs. the GLP-1 agent. Jörn comments on the high level of tolerability in the survodutide trials. Mazen shares his high hopes for GLP/glucagons and the triple agents. He goes back to review the survodutide data from the NEJM article. Mazen shares the late-breaker data that Vlad Ratziu presented on behalf of Stephen. This is a 96-week, triple biopsy study showing dramatic, sustained fibrosis improvement with a 30% delta for one level and a 21% delta for two levels. Jörn notes that the triple biopsies are demonstrate the durability of the agent against fibrosis. Roger notes this is particularly encouraging because of the previous pegbelfermin data showing loss of efficacy and tachyphylaxis. Naim concurs and adds that if the two-stage drop in fibrosis can be sustained, this would be a "big deal for the field" that might lead prescribers to think about FGF-21 as indication therapy with a "more tolerated" oral later on.   

Are you taking an ACE-Inhibitor for high blood pressure? If so have you experienced a dry cough? It literally can be linked to your medication and we discuss how easily you can get rid of this cough just by talking to your doctor today.Eating the standard American diet puts anyone at risk for developing fatty liver disease. It may sound benign, but for those where fatty liver disease causes chronic inflammation (even if not obese), 12% of those will be in need of a liver transplant, tune in to see how to avoid this complication.Rezdiffra, a new medication that uses the thyroid binding sites inside the liver to defeat fibrosis, could this be the way to defend the liver from years of processed foods?

This conversation re-introduces us to Sober Livers Founder/Visionary Jenn Jones and introduces us to Beth Lehman, Principal Strategic Advisor to Sober Livers and HOPE, a multi-element patient support program for people who have harmed their livers though AUD (Alcohol Use Disorder).As this conversation starts, we meet Beth Lehman, Principal Strategic Advisor for Sober LIvers, who discusses her disease background and personal history and adds one thing we might not know about her otherwise.After we meet Beth, Roger introduces the topic by discussing how the new nomenclature has broadened stakeholders' view of liver disease by incorporating AUD into the vision of steatotic liver disease through ALD and MetALD. In the aftermath of the new nomenclature uptake, Sober LIvers joined forces with the Fatty Liver Foundation and came to SurfingMASH's attention this way.Jenn introduces HOPE, which stands for Healing Others with Peers and Education, an organization that provides peer support for people who have harmed their bodies due to  AUD, while simultaneously advocating for "people to understand the disease better."  Some peers will be living with cirrhosis, while others will be post-transplant. Patients may have other metabolic system issues.  After sharing how hard it was for her to confront her truth, Beth notes that while she has been involved in several different programs, none have had subgroups for people who harmed their bodies through AUD...which is why she believes this group is needed so badly.

This conversation revolves largely around two Big Data presentations Hannes Hagstrom's team is sharing at the EASL Congress. Every other panelist has at least one meaningful comment to make about the future of Big Data in MASLD.Hannes describes two big data studies of his own, "very much Big Data, but it's not omics." One examined 860,000 residents of Stockholm who took a liver test between 2010-2022 seeking to estimate liver and cardiovascular risk. It relied on a tool from Stefano Romeo's group called the Fibrotic Mass Index. The results demonstrated the prediction of liver-related and cardiovascular-related outcomes.The other study relied on the same dataset to build a prediction model for liver-related outcomes in the general population. Instead of relying on a dedicated test like FIB-4, which has false results on both sides, this assimilates five simple parameters (ALT, AST, GGT, ender, age) and proves to be far more accurate at risk assessment than FIB-4. The study team will also present a small, web-based calculator "where people can go to estimate the risk." The tricky part, Hannes notes, is where to set a tolerable risk threshold. Jörn, thinking about the 860,000 sample, asks, "How much data is big enough?" Hannes notes that if the sample is big enough, we need not worry about statistical tests because we have true population-level data. Michelle considers the overarching implications of Hannes's comments: "I think a risk-based view of this disease makes a lot of sense." Aleksander and Roger concur that using a risk-based screening approach is preferable, in large part because it should allow a far larger share of resources to be devoted to those with significant disease. 

A person with rheumatoid arthritis and lupus develops new back pain in her mid-upper left side. It feels like “it's coming from under my ribs,” she says. First, it's diagnosed as arthritis, but interventions don't seem to make a difference. Finally, a year into this unremitting pain, a rheumatologist asks about her breathing and discovers she has developed a complication called pulmonary thrombosis, probably related to her autoimmune diseases. They start treatment and voilà, her back pain is gone. This is a good example of a case in which massage therapy was definitely NOT the best choice.   Resources: Dsouza, K.G. et al. (2023) ‘Management of interstitial lung disease in patients with autoimmune disease-related interstitial lung disease', Multidisciplinary Respiratory Medicine, 18(1), p. 890. Available at: https://doi.org/10.4081/mrm.2023.890.   Fibrosis as an autoimmune disease (no date) CPC - M. Available at: https://www.cpc-munich.de/en/research-projects/fibrosis-as-an-autoimmune-disease/index.html, https://www.cpc-munich.de/en/research-projects/fibrosis-as-an-autoimmune-disease/index.html (Accessed: 3 May 2024).   3. Gole, S. and Bankole, A. (2024) ‘Nintedanib', in StatPearls. Treasure Island (FL): StatPearls Publishing. Available at: http://www.ncbi.nlm.nih.gov/books/NBK585049/ (Accessed: 8 May 2024).   Interstitial Lung Diseases - What Are Interstitial Lung Diseases? | NHLBI, NIH (2022). Available at: https://www.nhlbi.nih.gov/health/interstitial-lung-diseases (Accessed: 8 May 2024).   5. Kašiković Lečić, S. et al. (2022) ‘Management of musculoskeletal pain in patients with idiopathic pulmonary fibrosis: a review', Upsala Journal of Medical Sciences, 127, p. 10.48101/ujms.v127.8739. Available at: https://doi.org/10.48101/ujms.v127.8739.   6. Massage & Bodywork - MAY | JUNE 2021 (no date). Available at: https://www.massageandbodyworkdigital.com/i/1358392-may-june-     Host:   Ruth Werner is a former massage therapist, a writer, and an NCBTMB-approved continuing education provider. She wrote A Massage Therapist's Guide to Pathology, now in its seventh edition, which is used in massage schools worldwide. Werner is also a long-time Massage & Bodywork columnist, most notably of the Pathology Perspectives column. Werner is also ABMP's partner on Pocket Pathology, a web-based app and quick reference program that puts key information for nearly 200 common pathologies at your fingertips. Werner's books are available at www.booksofdiscovery.com. And more information about her is available at www.ruthwerner.com.        Sponsors:   Anatomy Trains: www.anatomytrains.com    Elements Massage: www.elementsmassage.com/abmp   Earthlite: www.earthlite.com  

- Today, I have an excerpt from an interview with Dr. David Amron from our Lipedema Worldwide Summit in 2016.- Dr. David Amron is a plastic surgeon specializing in liposuction for lipedema, practicing in Beverly Hills, California.- In this excerpt, Dr. Amron explains the pathophysiology of fibrosis in lipedema.

Is brain damage detectable on MRI in patients with Havana Syndrome? Find out about this and more in today's PeerDirect Medical News Podcast.

Iman Shumpert Denies Claims He Had Utilities Cut Off At Family Home Teyana Taylor Lives In With Their Children Amid Divorce Battle Dreamville Festival Trends As Fans Express Disappointment In This Year's Lineup & Question Why Ari Lennox Will Be Missing From The Event: ‘IDK What's Going On But Somebody Need To Fix It' Jalen Hurts Trends Online As Fans Drag His New Goatee-less Look: ‘He Looks Like A Tyler Perry Villain' TikTocker Goes viral for “Single Mom” video. What are your thoughts??? SZA Explains How ‘Painful' Fibrosis & High Risk Of Breast Cancer Led To The Removal Of Her Breast Implants: ‘They Ended Up Hurting Me' Cardi B Says ‘I Don't Play That Sh*t' After She ‘Ran Into Somebody' At Vanity Fair Oscars Party & Fans Are Convinced She's Talking About Saweeti “I wish she would have pushed Angel Reese. ... You 6'8”, don't push somebody that little." Kim Mulkey speaks after Kamilla Cardoso pushed Flau'jae Johnson in LSU-SC scuffle  Russell Wilson reportedly plans to sign with the Pittsburgh Steelers Offset Says He And Quavo Don't Owe It To The Public To Explain Where They Stand: ‘I Don't Feel Like I Owe It To People To Show We Love Each Other' Atlanta Rapper RX HECTOR Going Viral For The Way He Treated His Mom. Meek Mill Vows To Help Philadelphia Mayor w/ Education & Gun Violence Efforts Following Tragic Shooting That Left 8 Teens Injured, 1 In Critical Condition Megan Thee Stallion takes a shot of alcohol from a bottle that has a snake in it while in Japan GloRilla responds to a pastor using the lyrics to her new song "Yeah Glo!" during his sermon Deion Sanders daughter , Deiondra announces she is expecting  Mike Epps says that while filming ‘All About The Benjamins ‘ he used coc*. Jacky Oh's Family Removes GoFundMe To Save Her Home After DC Young Fly Said It Was ‘Fake' TMZ asks Damian Lillard if he has reached out to Glorilla after she expressed interest in him : “No comment, my brother.” 4Batz has signed an EP deal with Drake's OVO label, Rick Ross's BM Tia Kemp Ran Into Gayle King At The Airport & Said She Needed To Be On Her Show, Gayle Replied : “and what would we be talking about.” Fans defend JT after having a bar booked for her solo tour Fan's tweet comparing Draya and Drake's situations goes viral WHOOPI GOLDBERG, 68, DEFENDS COUPLES WITH AGE GAPS WHILE REVEALING ONE OF HER LAST BOYFRIENDS WAS 40 YEARS OLDER THAN HER. Trey Songz Hosts A Meet & Greet With His Fans In Baltimore. Ally Lotti lists another batch of Juice Wrld's personally worn items for sale on OnlyFans Lil Durk's album '7220' has now spent 100 weeks on the Billboard 200 Boosie feels insulted by the Pelicans for only offering him $1K to perform. 'Atlanta Hawks pay a lot more,' he says Video goes viral of LeBron James sitting courtside with Lakers' owner Jeanie Buss Popular watch expert Nico Leonard expose Rick Ross for wearing a fake green AP watch $3M watch Drake trends on social media after fans are alleging that Drake is dating Latto's sister after a video of them seemingly leaving a restaurant together surfaced. Shannon Sharpe reveals he made more money off his Katt Williams interview than he made in any year he played in the NFL Anthony Joshua just knocked out Francis Ngannou in the 2nd round According to DJ Akademiks, Meek Mill's new EP for “Heathenism” sold 6k units first week Mike Epps says before he passes away he wants to learn how to treat a woman 100% right: “I've never treated a woman right... this is one of my dreams.” He's currently 53 years old Nelly says the 2000's era of music was the "toughest era in hip-hop ever."

Editor-in-Chief Sue Yom hosts Dr. Lachlan McDowell, a consultant Radiation Oncologist at the Princess Alexandra Hospital and the first author of a new paper this month, "A longitudinal study evaluating sexual health outcomes and prioritization in patients undergoing chemoradiation for human papillomavirus-associated oropharyngeal cancer," Dr. Jie Deng, Professor of Nursing, Senior Fellow at the Leonard Davis Institute of Health Economics, and Faculty Director of the Laboratory of Innovative & Translational Nursing Research at the University of Pennsylvania, and Dr. Barbara Murphy, Professor of Medicine, Hematology and Oncology Division Director, and Director of the Pain and Symptom Management Oncology Services at Vanderbilt University. Drs. Deng and Murphy were the first and last authors on a second paper this month, Longitudinal Pattern of Lymphedema and Fibrosis in Patients with Oral Cavity or Oropharyngeal Cancer: A Prospective Study.

Commentary by Dr. Valentin Fuster

In this episode, we review the high-yield topic of ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Gadolinium-Associated Nephrogenic Systemic Fibrosis⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ ⁠from the Renal section. Follow ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Medbullets⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ on social media: Facebook: www.facebook.com/medbullets Instagram: www.instagram.com/medbulletsofficial Twitter: www.twitter.com/medbullets Linkedin: https://www.linkedin.com/company/medbullets