Relationship between non-invasive tests, clinical outcomes and liver biopsy among people with MASH under real-world conditions.

Challenge

While liver biopsy remains the reference standard for MASH assessment, the relationship between biopsy-derived histological change and actual incidence of clinical outcomes in real-world patients—and whether non-invasive FIB-4 changes track those outcomes equivalently—had not been established at scale.

Solution

A TARGET-NASH analysis using patients with paired biopsies and serial FIB-4 measurements assessed the association between FIB-4 category transitions and the incidence of cirrhosis, decompensation, and composite clinical events, providing direct real-world validation of FIB-4 as a clinical outcome surrogate.

Impact

Establishing that FIB-4 category worsening predicts clinical outcomes with similar directionality to histological progression supports the regulatory acceptability of NIT-based endpoints and directly addresses the long-standing challenge of linking non-invasive markers to meaningful clinical events in MASH trials.