Relationship between liver biopsy fibrosis stage and clinical outcomes among persons with MASLD/MASH.

Challenge

Clinical trial sponsors needed real-world evidence confirming that fibrosis stage—as assessed by liver biopsy—is associated with meaningful differences in clinical event rates in the MASLD population, to justify histological improvement as a surrogate endpoint with clinical meaningfulness.

Solution

The TARGET-NASH cohort was used to analyze clinical outcomes stratified by baseline fibrosis stage and fibrosis trajectory (stable/improving vs. worsening) across paired liver biopsies, quantifying incidence rates of cirrhosis progression, decompensation, HCC, liver transplant, MELD change, cancer, and all-cause mortality.

Impact

Demonstrating that higher baseline fibrosis and worsening fibrosis trajectory are associated with significantly higher clinical event rates across multiple endpoints validates histological fibrosis as a clinically meaningful surrogate outcome and directly supports the regulatory acceptability of biopsy-based endpoints in MASH trials.