S2638 Impact of Statins on Recurrence and Survival in Patients With Hepatocellular Carcinoma Following Curative Surgery: A Systematic Review and Meta-Analysis

Introduction: The incidence of hepatocellular carcinoma (HCC) is rising and contributes significantly to the global and US cancer burden. Statins, through their anti-inflammatory, anti-angiogenic, and immunomodulatory properties are increasingly recognized as an adjunct in HCC management. Their impact on patients with HCC undergoing curative surgery, such as hepatic resection or transplantation has been associated with improved outcomes in numerous cohort studies. This systematic review and meta-analysis provides an updated study on the association between statins and recurrence and survival outcomes in patients with HCC. Methods: A comprehensive search of PubMed and Google Scholar through April 2025 was performed to identify all cohort studies evaluating the effect of statin use in HCC patients following hepatic resection or transplantation. HCC-recurrence, overall-survival, recurrence-free survival, all-cause mortality and HCC-related mortality were evaluated. For analysis, risk ratios (RR) were calculated from raw data, and hazard ratios (HRs) were extracted where reported. Results: A total of 15 studies met inclusion criteria, which included 4,524 patients in the statin group and 49,935 in the non-statin arm. Statin therapy was linked to a significant reduction in HCC-recurrence (HR = 0.63, 95% CI: [0.53-0.74], P < 0.00001), improvements in overall-survival (HR = 0.49, 95% CI: [0.45-0.53], P < 0.00001), recurrence-free survival (HR = 0.59, 95% CI: [0.56-0.63], P < 0.0001) along with reductions in all-cause mortality (RR = 0.30, 95% CI: [0.13-0.68], P < 0.004) and HCC-related mortality (RR = 0.34, 95% CI: [0.22-0.52], P < 0.00001). Subgroup analysis for the outcome of HCC-recurrence was conducted based on whether statins were used alone or in combination with other medications. The analysis displayed no statistically significant differences between subgroups (P = 0.81). Conclusion: Statin therapy was associated with decreased recurrence of HCC and improved survival outcomes, highlighting its potential use as an adjunct therapy following curative surgery in HCC. Validating these findings in a robust randomized control trial, including assessment of treatment dosage and duration, is needed, with at least one active trial currently underway.