Statin use and risk of hepatocellular carcinoma in metabolic dysfunction-associated steatotic liver disease: A national retrospective cohort study

Abstract Statins may reduce hepatocellular carcinoma (HCC) risk regardless of metabolic dysfunction-associated steatotic liver disease (MASLD) status. However, it remains unclear whether long-term statin use in MASLD patients lowers HCC risk to levels seen in individuals without steatotic liver disease (SLD). This study examined the impact of long-term statin use on HCC risk in MASLD, compared to those without SLD. We used the Korean National Health Insurance database including 251,061 adults aged ≥40 years. Hepatic steatosis was defined using a fatty liver index cutoff of 30. Statin use was defined as cumulative prescribed days for four years, and participants were grouped by statin duration and MASLD status. Multivariate Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (95% CIs) for HCC incidence from 2011 to 2019, during which 812 events occurred. Long-term statin use was associated with a reduced risk of HCC. Overall, the MASLD group exhibited a higher HCC risk compared to the non-SLD group. However, we found that the HCC risk in the MASLD group who used statins for more than 180 days was lower than that of the statin non-users without SLD (aHR, 0.64; 95% CI, 0.42-0.97). Statins showed a protective effect against HCC regardless of MASLD status, suggesting long-term statin use may mitigate the impact of hepatic steatosis on HCC development. Further clinical trials are needed to validate the effect of statin therapy in reducing HCC risk in patients with MASLD.