Last week, roughly 5,000 liver community stakeholders gathered in London for the 2022 International Liver Congress (#ILC2022,) the first major hepatology Congress to be held in person since the start of the pandemic (smaller, but very valuable, meetings like NASH-TAG, LiverCONNECT and Paris NASH have taken place with an in-person component, but the International Liver Congress and The Liver Meeting have not). On the last full day of the program, several vitally important drug development studies were presented during the late-breaker and dedicated sessions. The conversations in this episode will review some of the most important findings
This particular conversation includes reactions to the two major resmetirom presentations from the rest of our panel.
It starts with Jörn Schattenberg responding to the spleen and liver volume statements in Stephen’s presentation. He signals partial agreement and acceptance, then goes on to comment on ways the study methodology might have led to clearer volume data to interpret. In the end, though, he notes that other papers have linked spleen volume to clinically significant changes in portal hypertension. Stephen acknowledges Jörn’s comments and suggests that the upcoming MAESTRO Outcomes study might be an excellent place to resolve these issues.
Mazen Noureddin provides a more upbeat assessment of this data. He notes that when treating patients, the positive signs he seeks are reduction in spleen size and liver volume accompanied by a change in platelets. Since all three of these occurred in the cirrhotic cohort, he is somewhat optimistic about what future studies will prove. On the MAESTRO NAFLD-1 Phase 3, he states that this is the first trial he can recall (perhaps the first, period) where MRE is reduced. He “hopes this is fibrosis” and is excitedly awaiting confirmation when biopsy results are released.
Michelle Long agrees with Mazen and further notes that in the non-cirrhotic trial, the idea that patients missed two months of doses made the results more “generalizable” to what we might expect in standard clinical practice. Louise Campbell follows this up with the statement that many MAESTRO NAFLD-1 patients will likely be referred back to primary care for treatment and expresses her confidence that resmetirom might be a good option for PCPs when treating these patients.
The rest of the season focused on issues of biomarker inaccuracy. Jörn shares results from a presentation by Jerome Boursier on the accuracy of FIB-4 in Type 2 Diabetes patients and an analysis of the MAESTRO NAFLD-1 data he presented. In his presentation, 26% of patients with NAS >= 4 and biopsy-confirmed F2 or F3 NASH had normal ALT scores, and 80% had ALTs less than 2x normal. In Germany, where ALT is the test PCPs conduct before referring patients, Jörn expressed concerns about how many patients needing treatment are missed due to false ALT negatives. The rest of the discussion centers around defining the proper use of FIB-4 and areas with vast potential for misuse.