S5 - E4.6 - From The Vault: What a NASH Disease Model Reveals About Treating Advanced Fibrosis

Send us Fan MailTwo years ago, Surfing the MASH Tsunami conducted two episodes with Chris Estes, then the chief modeler for the Center for Disease Analysis Foundation exploring issues around CDAF's then-recent publication of a NASH/MASH disease model. This conversation centers on issues of advanced fibrosis. We thought it might be interesting to look back at that episode in lieu of today's topic. Here are the summary notes from 2022: This conversation starts with Chris Estes describing the processes he and his colleagues at the Center for Disease Analysis Foundation have used to build a disease model for NAFLD and NASH prevalence in 15 countries. Chris discusses some of the unique challenges that modeling NASH presents. Among other items, these include (a) spontaneous regression of disease; (b) "excess" mortality (mortality not from liver disease where NASH is a contributing factor); and (c) interplay of demographics (gender, age, race, etc.) and co-morbidities (most notably Type 2 diabetes) with disease.When Chris ends his initial comments, Jörn Schattenberg asks about the viability of using obesity as the anchor for increasing prevalence estimates instead of diabetes, noting the varying definitions of BMI across countries. Chris notes that obesity is imperfect but adds that we have robust, stable, long-term obesity data bases in most countries, whereas diabetes estimates are newer and many people with diabetes to not recognize they have the disease.The last element in this conversation starts with Alina Allen noting that for clinical trial development, researchers test patients with a range of diagnostics. As a result, they do not need to develop estimates based on (or even linked directly to) obesity or diabetes. Alina asks what models can tell us that can help bring down high placebo rates in double-blinded, placebo-controlled clinical trials. Chris mentions meta analyses as recently as seven years ago that exhibited negative disease progression over time and adds that any assessment of F3 (or even F2) fibrosis is affected by concomitant disease.This conversation is sponsored by Resoundant, a Mayo Clinic company and the developers of Magnetic Resonance Elastography. MRE is widely available with over 2000 locations worldwide, and can be done as a low-cost, rapid exam in just 5 minutes. Together with PDFF, this quantitative exam is called an Hepatogram – a powerful non-invasive alternative to liver biopsy in many cases. For more information, visit www.resoundant.com on the web.