masld/nafld

Hepatology researchers and key opinion leaders Profs. Laurent Castera and Scott Friedman join Louise Campbell and Roger Green in the final element of our review coverage of TLM 2023. This far-ranging conversation moves beyond MASLD/NAFLD and MASH/NASH to consider an array of topics.

The episode starts with Roger asking the other guests for their general impressions of the meeting. Three key insights: 

1.    "Pre-pandemic" levels of interaction and discussion among attendees

2.     Online meeting app was a "fail", becoming a topic of conversation in its own right while fostering confusion

3.    In the "frenzy" about the anticipated resmetirom approval and other MASH drugs approaching market,  we shouldn't overlook that patients with PBC will soon have two new exciting PPAR agents, elafibranor and seladelpar. As Scott notes, we also learned about promising modes of action for PSC so, overall, a promising meeting for rare cholestatic diseases. 

The rest of this discussion covers multiple topics, key among them: 

 ·      Impact of FGF-21 and FGF-19 agents on patients with compensated cirrhosis. Roger is optimistic that agents might provide improvement. Scott is more pessimistic because we do not have agents addressing the unique mechanistic challenges in cirrhosis vs. advanced fibrosis. Both agree that agents on the horizon can buy time until curative or regressive medications arrive. 

·      AI-based analysis. Roger bridges to Stephen Harrison’s presentation of HistoIndex analysis of resmetirom that produces an estimate of 54% efficacy vs. 34% placebo. He comments that given this analysis and that bariatric surgery studies tell us fibrosis regression may take five years, the FDA one-year standard might be so stringent as to be misleading. 

·      Bariatric surgery. Laurent refers to a presentation from Phillippe Mathurin's group demonstrating that in patients post-bariatric surgery, MASH resolution and fibrosis regression clearly lead to improved outcomes. 

·      NITs. Laurent discusses a poster from a multi-country 16,000-patient cohort that did not confirm liver stiffness as leading to a decline in MALO over a two-year period but anticipates more robust findings over time. 

·      VCTE-based analysis. Louise discusses two posters with analyses based on FibroScan. The first, from the Virginia Commonwealth University and the VA, found that liver stiffness correlates with success in liver transplant and that CAP can predict the risk of future MI in these patients. She notes that CAP of 270 served as "its own parameter" in predicting time to mortality. 

·      Nomenclature. Roger notes that a Saturday morning session resolved the two most pivotal outstanding issues about the effect of nomenclature change on scientific development. FDA signaled that the agency views old and new nomenclature terms as interchangeable. NIMBLE and LITMUS analysis determined that patient mapping is also interchangeable.

·      Impact of triple-agents. Presentations at this conference confirm that triple agents addressing GLP-1, glucagon and GIP can have bariatric surgery-level impact on liver fat and reduce the entire disease burden. 

Interspersed between these topics are a range of insights on cirrhosis disease models, regulatory slowness in moving on from current conditional efficacy metrics, treater supply vs. patient demand, "stigma", and basic science. This is a high-level view of an information-dense conversation. Listen to learn more and hear all the details.