This week, Surfing the NASH Tsunami returns to a subject we have explored from time to time over the past two years: helping patients with cirrhosis. While the immediate stimulus for doing so was the semaglutide late-breaker at #ILC2022, our more general interest is that many patients with cirrhosis will start to decompensate and decline in a fairly short period of time. This conversation begins to explore the ability of currently available medications to cause fibrosis regression in patients with cirrhosis.

Can Today’s Medicines Cause Fibrosis Regression in Cirrhosis Patients?

This conversation starts with Lars posing a question to Jörn: does he believe that a “drug like sema[glutide]” can inhibit the progression of fibrosis, even though the #ILC2022 late-breaker showed no significant level of fibrosis regression over a 48-week period. Jörn replies that the study demonstrated that semaglutide was safe and demonstrated some effects (on transaminase levels, for example), but nothing on fibrosis. He then turns the question back to Lars to ask what metabolic or systemic effects we might measure as a precursor to fibrosis regression or even lack of progression.

Lars points to subclinical signs of possible portal hypertension as one place to look. In this context, he notes that increases in spleen volume as modest as 20-30% can be linked to increasing fibrosis levels and possibly changes in portal pressure. As a result, he suggests, looking at changes in portal pressure might be a fruitful area for exploring the ability of a medication to regress fibrosis or even just to stop progression. Lars notes this could be reduced inflammation that has not yet translated into fibrosis regression. As he points out, bariatric studies show it can take years to regress fibrosis.

Roger asks the group which parameters they consider signs of fibrotic stabilization or regression. Jörn notes Lars’s earlier comment about HVPG and asks which measures correlate with it. He mentions varices and ascites as signs to watch as the disease progresses. Finally, he asks about how well patients with compensated cirrhosis perform on other performance metrics.

Lars answers that performance is “not that bad in terms of other effects” and goes on to describe some of the other measures he and others are exploring. As the conversation ends, Lars points out that reducing activation of stellate cells would be a good thing in itself, regardless of whether or how long it takes to lead to fibrosis regression.