BACKGROUND AND AIMS: Statins have been proposed as hepatoprotective agents in chronic liver disease (CLD); however, evidence from existing systematic reviews-including observational studies and clinical trials-is inconsistent and affected by substantial overlap. We conducted an umbrella review to synthesize the available evidence on the associations between statin use and hepatological outcomes in CLD patients, while addressing study overlap. DESIGN: PubMed, EMBASE, and Cochrane Library were searched up to September 2025 for systematic reviews of statin therapy in CLD. Methodological quality was evaluated using AMSTAR-2. Study overlap was assessed using corrected covered area (CCA) and minimized via hierarchical exclusion prioritizing methodological quality, comprehensiveness, and recency. Random-effects meta-analyses with bias assessments were conducted. RESULTS: Of 850 records screened, 17 systematic reviews (229 unique studies; 10,515,877 participants from 34 countries) were included after overlap adjustment (CCA = 5.79%). Statin therapy was associated with 46% reduction in hepatocellular carcinoma (HCC) risk (HR 0.54, 95% CI 0.48-0.59; I² = 46.7%) and 46% reduction in hepatic decompensation (HR 0.54, 95% CI 0.49-0.59; I² = 0.1%); these estimates derive predominantly from observational studies and should be interpreted as associations rather than causal effects. Geographic heterogeneity was observed: Asian populations showed stronger benefits (HCC HR 0.49, 95% CI 0.45-0.53; I² = 0%) compared with Western populations (HCC HR 0.71, 95% CI 0.52-0.96; I² = 95.7%; p = 0.003). Statin use also associated with reduced all-cause mortality (HR 0.65, 95% CI 0.52-0.81), though with substantial heterogeneity (I² = 80%). In contrast, available RCT-based evidence does not consistently confirm these associations for decompensation or mortality outcomes. CONCLUSIONS: Statin use is consistently associated with reduced HCC risk and hepatic decompensation in CLD patients, particularly in Asian populations, though these findings derive predominantly from observational evidence subject to potential confounding. These associations support the continued use of statins in patients with CLD and cardiovascular indications where these are otherwise indicated, with potential additive hepatoprotective effects. These results underscore the urgent need for adequately powered randomized trials to clarify the boundaries of safety and efficacy in this high-risk population.
Cattazzo et al. (Mon,) studied this question.