The Effect of Statin Therapy on the Overall Survival of Patients with Hepatocellular Carcinoma: A Single-Center Experience

Background: Statins have pleiotropic anti-inflammatory, antifibrotic, and potential antineoplastic effects. Although several studies have linked statin exposure to lower hepatocellular carcinoma (HCC) incidence, their effect on survival after HCC diagnosis remains uncertain. We evaluated whether statin therapy before HCC diagnosis was associated with overall survival in a real-world cohort. Methods: We performed a retrospective single-center cohort study of consecutive patients with HCC managed at a tertiary referral center between January 2000 and January 2025. Demographic, clinical, laboratory, tumor-related, and treatment variables were collected at diagnosis and during follow-up. Patients were classified according to statin use before HCC diagnosis. Overall survival (OS) was assessed using Kaplan–Meier analysis and Cox proportional hazards regression. Results: Overall, 190 patients were included; 172 (90.5%) were male, 136 (71.6%) had cirrhosis, and 42 (22.1%) received statins. Statin users more frequently had diabetes mellitus, elevated body mass index and arterial hypertension, but baseline liver function, alpha-fetoprotein levels, tumor burden, and treatment allocation were broadly comparable between groups. Among 159 patients with available survival data, statin users had longer OS than non-users (mean 82.5 vs. 41.7 months; median 57 vs. 31 months; log-rank p < 0.001). In univariate Cox analysis, statin therapy was associated with reduced mortality risk (HR 0.45, 95% CI 0.28–0.70, p < 0.001). This association remained significant across multivariable models adjusting for baseline liver function, tumor stage, vascular invasion, and diagnostic era. Conclusions: Pre-diagnostic statin therapy was independently associated with improved OS in patients with HCC. These hypothesis-generating findings warrant prospective multicenter validation and careful assessment of confounding by indication.