Association between statin use and the prognosis of hepatocellular carcinoma after resection: a nationwide cohort study

Background The majority of patients with hepatocellular carcinoma (HCC) following hepatic resection experience tumor recurrence. Statin use is associated with a reduced risk of HCC development; however, the association be-tween statin use and the prognosis of HCC after resection remains unclear. We aimed to investigate the effect of statin use on the prognosis after hepatic resection among patients with HCC.Methods A nationwide cohort study was performed with data from the National Health Insurance Service Database in Korea. Among 65,101 HCC patients who underwent hepatic resection between January 2002 and December 2017, we included 21,470 patients. For validation, a hospital-based cohort of 3366 patients with very early or early-stage HCC who received curative-intent hepatic resection between January 2010 and December 2018 was analyzed. Recurrence-free survival (RFS) and overall survival (OS) was compared between statin users and non-users.Findings Among the nationwide cohort of 21,470 patients, 2399 (11.2%) used statins and 19,071 (88.8%) did not. Among the hospital cohort of 3366 patients, 363 (10.8%) used statins and 3003 (89.2%) did not. In the propensity score-matched nationwide cohort, statin users had better RFS (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.56-0.64; P < 0.001) and OS (HR, 0.49; 95% CI, 0.45-0.53; P < 0.001), with a duration-response relationship. In the propensity score-matched validation hospital cohort, statin treatment was significantly associated with better RFS (HR, 0.73; 95% CI, 0.59-0.90; P = 0.003) and OS (HR, 0.48; 95% CI, 0.32-0.72; P < 0.001). The beneficial effects of statins were more prominent in non-cirrhotics, tumors sized >= 3 cm, tumors with microscopic vascular invasion, or early HCC recurrence (<2 years after resection).Interpretation Statin use was associated with a better prognosis in a population-based cohort of patients with HCC after hepatic resection, which was further validated in a large hospital-based cohort.