Angiotensin-Converting Enzyme Inhibitors and Hepatocellular Carcinoma Risk in Patients With Chronic Hepatitis B and Hypertension: A Nationwide Dose-Response Cohort Study.

INTRODUCTION

Chronic hepatitis B virus (HBV) infection is a leading cause of hepatocellular carcinoma (HCC). Angiotensin-converting enzyme inhibitors (ACEIs) may reduce HCC risk by modulating hepatic fibrogenesis, but population-level evidence remains limited.

METHODS

We conducted a nationwide cohort study using Taiwan's National Health Insurance Research Database (2010-2020), including adults with chronic HBV and hypertension. ACEI use was defined as ≥28 cumulative defined daily doses. We applied a new-user design, propensity score matching, time-varying Cox models, and competing risk analysis to assess incident HCC.

RESULTS

After 1:1 propensity score matching, 118,715 patients were included in each group. ACEI users had a significantly lower HCC risk than nonusers (adjusted hazard ratio [aHR], 0.66; 95% confidence interval, 0.64-0.69). A strong dose-dependent effect was observed, with the highest cumulative defined daily dose quartile demonstrating the greatest risk reduction (aHR, 0.29; 95% confidence interval, 0.26-0.32). This protective association persisted regardless of concurrent nucleos(t)ide analogues (NAs) therapy. Furthermore, treatment persistence (>1 year) was associated with lower HCC risk compared with early discontinuation (aHR, 0.62 vs 0.71).

DISCUSSION: ACEI use was associated with a robust, dose-dependent reduction in HCC risk among chronic HBV patients with hypertension. These findings highlight the translational potential of repurposing ACEIs for HCC chemoprevention, particularly for hypertensive HBV carriers currently ineligible for antiviral therapy.