Association between antihypertensive medications and hepatocellular carcinoma risk in individuals with metabolic dysfunction–associated steatotic liver disease (MASLD) without cirrhosis

INTRODUCTION AND OBJECTIVES: Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major risk factor for HCC. Antihypertensive medications have been hypothesized to influence HCC risk through metabolic and anti-inflammatory mechanisms. This study aimed to evaluate the association between antihypertensive medication use and HCC risk in individuals with MASLD. MATERIALS AND METHODS: Records from the Taiwan National Health Insurance Research Database (NHIRD) from 2001 to 2019 were retrospectively reviewed. Patients ≥ 18 years old with MASLD were eligible for inclusion. Patients with preexisting HCC, heavy alcohol use, cirrhosis, viral hepatitis, or autoimmune liver diseases were excluded. Associations between antihypertensive medication use and HCC risk were evaluated using Fine-Gray subdistribution hazard models, treating mortality as a competing event. RESULTS: A total of 15,575 patients were identified, and 563 (3.6%) developed HCC. In multivariable competing-risk analyses, renin-angiotensin-aldosterone system (RAAS) inhibitor use was independently associated with a lower cumulative incidence of HCC. In contrast, the association between calcium channel blocker (CCB) use and HCC risk was attenuated after adjustment and did not consistently reach statistical significance. Stratified analyses demonstrated heterogeneity across clinical subgroups, particularly according to chronic kidney disease (CKD) and heart failure (HF) status. CONCLUSIONS: RAAS inhibitor use was associated with reduced HCC risk in individuals with MASLD after accounting for competing mortality. These findings suggest a potential role for RAAS inhibition in modulating MASLD-related hepatocarcinogenesis, warranting further prospective and mechanistic investigation.