Efficacy of simvastatin as adjunctive therapy in liver cirrhosis: an updated meta-analysis of randomized controlled trials

The clinical benefit of simvastatin as an adjunctive treatment in liver cirrhosis remains inconclusive, with prior syntheses becoming outdated after the publication of the largest trial on the topic. This updated meta-analysis aimed to evaluate the therapeutic impact of simvastatin in cirrhotic patients. A systematic search was conducted in PubMed, Embase, Cochrane Library, and ClinicalTrials.gov using MeSH terms related to “Simvastatin” and “Liver Cirrhosis.” Randomized controlled trials (RCTs) comparing simvastatin to placebo or any other drugs were included. Nine RCTs, including 966 patients, were analyzed. Simvastatin showed no statistically significant effect on all-cause mortality, although a borderline trend toward a 37% relative risk reduction was observed [risk ratio (RR): 0.63; 95% confidence interval (CI): 0.38–1.04; P = 0.07], suggesting a potentially clinically meaningful effect. No significant differences were found in bleeding (RR: 0.70; 95% CI: 0.45–1.08), development of ascites (RR: 0.91; 95% CI: 0.69–1.21), hepatorenal syndrome (RR: 0.85; 95% CI: 0.64–1.87), hepatic venous pressure gradient (standardized mean difference [SMD]: −0.19; 95% CI: −0.49 to 0.11), wedged hepatic venous pressure (SMD: −0.11; 95% CI: −0.44 to 0.23), free hepatic venous pressure (SMD: 0.04; 95% CI: −0.21 to 0.29), and adverse events (RR: 1.04; 95% CI: 0.95–1.15), serious adverse events (RR: 0.93; 95% CI: 0.75–1.15), and musculoskeletal adverse events (RR: 1.27; 95% CI: 0.87–1.85). Overall, simvastatin did not demonstrate statistically significant reductions in cirrhosis-related complications. Nevertheless, the observed trend toward lower mortality suggests a possible protective effect that existing trials may be underpowered to confirm. Larger, well-designed RCTs are warranted to clarify its impact on survival outcomes.