Statins were not associated with hepatocellular carcinoma after controlling for time-varying confounders in patients with diabetes

Abstract

Background and ObjectivesWe examined the association between statin use and hepatocellular carcinoma (HCC) incidence in patients with diabetes using marginal structural models (MSMs) estimated by inverse probability weight (IPW), which adjusts for time-varying confounders that are also mediators, and we compared the results with conventional regression methods. MethodsThis retrospective cohort study included 245,122 patients with type 2 diabetes who were new users of lipid-lowering drugs identified using the claims data of a universal health insurance program. Statin exposure was time-updated every three months during the follow-up period. Stabilized IPW was calculated and accounted for chronic liver diseases considering as time-dependent confounders affected by past statin exposure. ResultsOver a median follow-up of 5.2 years, 1,694 patients developed HCC. In the conventional regression analysis, the hazard ratio of HCC associated with statin use was 0.88 (95% confidence interval CI: 0.79–0.97) after adjusting for baseline covariates and 0.97 (95% CI: 0.87–1.08) after additionally adjusting for time-varying covariates. The hazard ratio increased to 1.11 (95% CI: 0.94–1.31) using the MSM approach. ConclusionStatin use was not associated with the risk of developing HCC in patients with diabetes. Our findings highlight the importance of controlling time-varying confounders in observational studies.