Impact of Antihypertensive and Lipid-Lowering Agents on Hepatocellular Carcinoma Risk in Patients with Fatty Liver Disease and Diabetes.

Background/aim: This study aimed to evaluate 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).

Method: Using data from Korea Health Insurance Review and Assessment Service, 212,443 FLD-T2D patients were analyzed through Cox regression, propensity score matching (PSM), and Kaplan-Meier analysis. The analysis considered medication use and its relation to HCC development. Cohort admission day was set as the date of the first oral hypoglycemic prescription.

Results: The multivariate Cox regression analysis revealed that old age, male sex, chronic viral hepatitis, alcoholic liver disease, liver cirrhosis, using a combination of insulin and oral hypoglycemic agents for antidiabetic treatment, and calcium channel blocker (CCB) use were significantly correlated with higher HCC development risk, whereas dyslipidemia and statin, ezetimibe, and fibrate use was correlated with lower HCC risk, in the study cohort of 212,443 patients. 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 risk of HCC development even after PSM. In contrast, CCB use was linked to an elevated HCC risk (HR = 1.35, 95% CI = 1.05-1.72, P = 0.019), highlighting the differential impact of various medications on HCC incidence.

Conclusion: The use of specific medications, such as statins and fibrates, may offer protective effects against HCC in patients with FLD-T2D, whereas that of CCB may increase the risk. This underscores the importance of tailored medication strategies for the management of chronic conditions.