Impact of Antihypertensive, Lipid-Lowering, and Antiplatelet Agents on Development of Hepatocellular Carcinoma in Patients with Fatty Liver Disease and Diabetes

Abstract We evaluated the effects of antihypertensives, lipid-lowering agents, and antiplatelet medications on hepatocellular carcinoma (HCC) risk in patients with fatty liver disease (FLD) and type 2 diabetes (T2D). Data on 212,443 patients with FLD and T2D, obtained from the Korea Health Insurance Review and Assessment Service, were analyzed. Cohort admission day was set as the date of the first oral hypoglycemic agents (OHAs) prescription. Multivariate Cox regression analysis revealed that old age, male sex, chronic viral hepatitis, alcoholic liver disease, liver cirrhosis, insulin use, and calcium channel blockers (CCBs) were significantly correlated with a higher HCC risk, whereas statin, ezetimibe, and fibrate use was correlated with a lower risk of HCC development. Propensity score matching (PSM) was performed according to usage of statin, fibrates, and CCB. Patients who used statins (hazard ratio (HR)=0.58, 95% confidence interval (CI)=0.42-0.80, P=0.001) and fibrates (HR=0.46, 95% CI=0.22-0.93, P=0.031) showed a significantly lower HCC risk even after PSM. CCB use was linked to an elevated HCC risk (HR=1.35, 95% CI=1.05-1.72, P=0.019). Statins and fibrates may offer protective effects against HCC development in patients with FLD and T2D, whereas CCBs may increase the risk. Thus, tailored medication strategies are required for the management of chronic conditions.