Redefining End Points in MASH Cirrhosis

This editorial discusses the challenges of defining clinical trial endpoints for metabolic dysfunction-associated steatohepatitis (MASH) cirrhosis. While therapies like semaglutide and resmetirom show efficacy in non cirrhotic MASH, patients with cirrhosis require different endpoints such as preventing decompensation or achieving regression to non cirrhotic stages. The phase 2b trial of effluxifermin, an FGF21 analogue, failed to show significant fibrosis reduction in compensated MASH cirrhosis at 36 weeks, possibly due to heterogeneity in portal hypertension severity. The author advocates stratifying patients by clinically significant portal hypertension (CSPH) status in future trials, using noninvasive markers (e.g., liver stiffness and platelet count) to tailor endpoints: regression for early cirrhosis (no CSPH) and decompensation prevention for advanced cases (with CSPH). The editorial underscores the need for targeted therapies in this high risk population.

This editorial discusses the challenges of defining clinical trial endpoints for metabolic dysfunction-associated steatohepatitis (MASH) cirrhosis. While therapies like semaglutide and resmetirom show efficacy in non cirrhotic MASH, patients with cirrhosis require different endpoints such as preventing decompensation or achieving regression to non cirrhotic stages. The phase 2b trial of effluxifermin, an FGF21 analogue, failed to show significant fibrosis reduction in compensated MASH cirrhosis at 36 weeks, possibly due to heterogeneity in portal hypertension severity. The author advocates stratifying patients by clinically significant portal hypertension (CSPH) status in future trials, using noninvasive markers (e.g., liver stiffness and platelet count) to tailor endpoints: regression for early cirrhosis (no CSPH) and decompensation prevention for advanced cases (with CSPH). The editorial underscores the need for targeted therapies in this high risk population.