Multi-threshold analysis of the ELF Test versus histology for prognostication of disease progression and regression in MASH

BACKGROUND: Patients with metabolic dysfunction-associated steatohepatitis (MASH) with advanced fibrosis are at risk for progression to cirrhosis and clinical outcomes, but can also experience fibrosis regression. The aim of this study was to compare risk stratification by the Enhanced Liver Fibrosis (ELF) Test to histological staging to assess patients at risk of disease progression and those likely to experience histological regression. METHODS: Using pooled data from 6 large placebo-controlled trials of 2710 patients with advanced fibrosis due to MASH, 4 analyses of ELF and fibrosis stage were performed to evaluate the association with the following events: (1) liver-related clinical outcomes; (2) progression from bridging fibrosis to cirrhosis; (3) regression from bridging fibrosis; (4) regression from cirrhosis. Significance was assessed by interval likelihood ratio (iLR), Cox proportional hazard ratio (HR), and area under the receiver operator characteristic curve (AUROC). RESULTS: In 2304 participants (17.8 mo mean follow-up), there was a progressive rise in liver-related outcome risk with increasing baseline ELF score [<9.00 (0%), ≥9.00 to <9.80 (2%), ≥9.80 to <11.30 (4%), ≥11.30 to <12.80 (13%), ≥12.80 (40%)]. In 1414 patients with bridging fibrosis, increasing baseline ELF scores were associated with a higher risk of progression to cirrhosis [<9.80 (9%), ≥9.80 to <11.30 (18%), ≥11.30 (45%)] and a lower likelihood of histological regression. In 1690 patients with cirrhosis, increasing baseline ELF scores were associated with a lower likelihood of histological regression [<9.80 (33%), ≥9.80 to <11.30 (16%), ≥11.30 (6%)]. In all analyses, the ELF Test provided more detailed information than histology. CONCLUSIONS: The ELF Test adds risk strata that are significantly different from fibrosis staging for the prediction of clinical events and histological changes, thereby improving risk stratification.