Statin Therapy Independently Reduces Mortality and Liver Complications in Patients With Cirrhosis: An Updated Systematic Review and Meta‐Analysis

BACKGROUND: The role of statins in cirrhosis remains controversial. Historically restricted due to safety concerns, emerging evidence highlights potential pleiotropic benefits, though effects on mortality and decompensation remain uncertain. AIMS: To evaluate the effects of statin therapy on all-cause mortality, hepatic decompensation, hepatic venous pressure gradient (HVPG), and hepatocellular carcinoma (HCC) in cirrhosis. METHODS: We systematically searched major databases until July 2025 for randomised controlled trials (RCTs) and observational studies comparing statin therapy versus non-use in cirrhosis. Random-effects meta-analyses were performed. RESULTS: The meta-analysis included 25 studies (9 RCTs, 16 observational) with 81,992 patients. Statins reduced all-cause mortality in the overall analysis (unadjusted odds ratio 0.59; 95% CI: 0.48-0.71) and in RCTs (odds ratio 0.45; 95% CI 0.25-0.82), supported by a significant HVPG reduction. Conversely, statins reduced hepatic decompensation in the overall analysis (unadjusted odds ratio 0.56; 95% CI: 0.47-0.66) but not in RCTs (odds ratio 0.75; 95% CI: 0.52-1.09). Observational data indicated a protective association for HCC (adjusted hazard ratio 0.61; 95% CI: 0.46-0.82), and no RCT reported this outcome. CONCLUSIONS: Statin therapy is associated with improved survival in cirrhosis, supported mechanistically by reductions in portal pressure. Observational evidence suggests benefits for decompensation and HCC, though these remain uncertain due to residual confounding. Large-scale, long-term RCTs are needed to clarify the role of statins as disease-modifying therapy in cirrhosis.