Higher histologic liver fibrosis stages correlate with increased risk of cirrhosis and hepatic decompensationLiver Fibrosis Stages Linked to Higher Risk of Liver Failure

Metabolic dysfunction-associated steatohepatitis (MASH) and steatotic liver disease (MASLD) are progressive liver conditions that can lead to serious long-term outcomes and adverse clinical events. Histologic liver fibrosis is an accepted short-term surrogate end point used in pivotal clinical trials supporting conditionally approved MASH therapies. This study aimed to synthesize up-to-date published associations between histologic liver fibrosis and clinical outcomes, including several novel syntheses. A systematic literature review identified studies of MASH ± MASLD patients published January 2014 to November 2024 from Ovid MEDLINE, Embase and grey literature. Studies reporting hazard ratios (HRs) comparing the risk of relevant major adverse liver outcomes (MALO; e.g., cirrhosis, hepatic decompensation, hepatocellular carcinoma) and mortality by histologic liver fibrosis stage were included in meta-analysis. Pooled estimates were reported as HRs and 95% CIs. Of 2810 returned records, there were 32 eligible studies from 39 articles. Higher fibrosis stage was associated with increased risk of clinical outcomes. Risk of progression to cirrhosis was twofold higher in F3 versus F2 (2.05 [1.45, 2.90]). Risk of hepatic decompensation was >ten-times higher in F3-4 versus F0-2 (10.93 [6.31, 18.92]). Risk of MALO and all-cause mortality were also significantly higher in F4 versus F3 and versus F2, and in F3-4 versus F0-2. Results were directionally consistent among studies of MASH-majority (≥80% MASH) populations and individually reported HRs. Increased clinical risk with more advanced fibrosis and/or cirrhosis among patients with significant liver disease supports the value of histologic liver fibrosis as a short-term surrogate for long-term clinical outcomes.