S2610 Role of Simvastatin as an Adjunct Therapy in Liver Cirrhosis: An Updated Meta-Analysis of Randomized Controlled Trials

Introduction: The clinical efficacy of simvastatin as an adjunct therapy in patients with liver cirrhosis remains uncertain. Statins are believed to reduce portal pressure and suppress inflammation. We conducted a meta-analysis to assess the clinical impact of simvastatin in patients with liver cirrhosis. Methods: We performed a systematic literature search in PubMed, Embase, Cochrane Library, and ClinicalTrials.gov using MeSH terms for ‘Simvastatin’ and ‘Liver Cirrhosis’. All randomized controlled trials (RCTs) evaluating simvastatin as an adjunct therapy compared with controls were included. For continuous outcomes, standardized mean differences (SMDs) were pooled; for dichotomous outcomes, risk ratios (RRs) were calculated. All estimates were presented with 95% confidence intervals (CIs) and combined with a random-effects model. Results: Total 9 studies recruiting 1,014 patients were included. Four studies reported on the effect of simvastatin on mortality, with no significant difference observed between the simvastatin and control groups [risk ratio (RR): 0.63; 95% confidence interval (CI), 0.38 -1.04; P = 0.07]. Both groups were comparable in terms of complications such as Bleeding [RR 0.70, 95% CI 0.45 - 1.08; P = 0.10], new or worsening ascites [RR 0.91, 95% CI 0.69 - 1.21; P = 0.51], and development of acute kidney injury or hepatorenal syndrome [RR 0.85, 95% CI 0.649 - 1.87; P = 0.57]. There was no statistically significant difference in hepatic hemodynamic measurements such as hepatic venous pressure gradient (HVPG) [standardized mean difference (SMD) -0.19, 95% CI -0.49 - 0.11; P = 0.21], wedged hepatic venous pressure (WHVP) [ SMD -0.11, 95% CI -0.44 - 0.23; P = 0.53], and Free hepatic venous pressure (FHVP) [SMD 0.04, 95% CI -0.21 - 0.29; P = 0.76] between the 2 groups. Conclusion: This meta-analysis demonstrates that simvastatin as an adjunct therapy in patients with liver cirrhosis, does not significantly impact mortality, incidence of complications (including bleeding, ascites, and renal dysfunction) or hepatic hemodynamic parameters. Although statins have shown theoretical benefits in reducing portal pressure and inflammation, the current evidence does not support a clear clinical advantage of simvastatin in this population. Further high-quality, large scale and adequately powered randomized controlled trials are warranted to better clarify its potential role in the management of liver cirrhosis.