Efficacy and Safety of Statins in Patients with Liver Cirrhosis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials with Trial Sequential Analysis

Liver cirrhosis is a global health burden with high morbidity and mortality. Recent evidence suggests the benefits of statins in liver cirrhosis due to its pleiotropic effects. This systematic review and meta-analysis was conducted to evaluate the efficacy and safety of statins in patients with liver cirrhosis. PubMed, EMBASE, and Cochrane Library databases were systematically searched to identify all relevant randomized controlled trials (RCTs) regarding use of statins in cirrhosis. Risk ratios (RRs) or mean differences (MDs) with their 95% confidence intervals (CIs) were pooled for the outcomes, including overall mortality, hepatic venous pressure gradient (HVPG), cirrhosis-related complications, and adverse events. Heterogeneity was calculated. Trial sequential analysis (TSA) was performed. Thirteen RCTs were included. Statins significantly decreased the overall mortality (RR 0.63, 95% CI 0.47–0.84, I 2 = 0%), reduced HVPG (MD 0.96, 95% CI 0.35–1.57, I 2 = 19%), and increased the proportion of patients who achieved HVPG response (RR 1.88, 95% CI 1.04–3.38, I 2 = 62%). Statins were not associated with the incidence of acute-on-chronic liver failure, variceal bleeding, new or worsening ascites, hepatic encephalopathy, or acute kidney injury, but significantly reduced the incidence of spontaneous bacterial peritonitis (RR 0.35, 95% CI 0.16–0.75, I 2 = 0%). There was no significant difference in the incidence of any adverse events or serious adverse events between patients who received statins and those who did not. TSA suggested that further studies should be necessary to validate the efficacy of statins. Statins may reduce the overall mortality and HVPG in patients with liver cirrhosis. Additionally, statins can prevent from spontaneous bacterial peritonitis, but not other cirrhosis-related complications. The protocol was prospectively registered on the PROSPERO database (CRD420251000903).