A Pragmatic Clinical Prognostic Classification Suitable for Universal Application Stratifies Patients with NAFLD by Risk of Mortality and Both Hepatic and Extrahepatic Outcomes.

Challenge

Existing NAFLD prognostic classification systems required liver biopsy for accurate staging, limiting their applicability in community practice and clinical trial screening where biopsy is impractical. A pragmatic biopsy-free system validated against hard outcomes was needed for universal application.

Solution

The TARGET-NASH cohort was used to validate a three-tiered (Class A/B/C) prognostic classification based on FIB-4 and clinical-laboratory criteria against hard outcome incidence rates—mortality, liver events, MACE, and HCC—demonstrating stepwise outcome separation across risk strata.

Impact

Validating a universally applicable biopsy-free prognostic classification against hard outcomes provides a regulatory-grade risk stratification tool for MASH trial enrollment, clinical decision support, and health economic modeling applicable across both academic and community settings.