Association between daily aspirin therapy and risk of hepatocellular carcinoma according to metabolic risk factor burden in non-cirrhotic patients with chronic hepatitis B

Background: Several studies have demonstrated chemopreventive effects of aspirin against hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). Aims: To investigate the associations of aspirin use with risks of HCC, liver-related mortality, and major bleeding according to metabolic risk factor burden among non-cirrhotic patients with CHB. Methods: Using the Korean National Health Insurance Service database, we identified 282,611 non-cirrhotic adults with CHB. Data on obesity, diabetes, high blood pressure, and hypercholesterolemia were collected. Subjects were stratified into lower and higher metabolic risk groups (≤2 and ≥3 risk factors, respectively). Propensity score-matched cohorts of aspirin users and non-users were generated. Risks of HCC, liver-related death and major bleeding were analyzed. Results: During the median follow-up of 7.4 years, positive associations between metabolic risk factor burden and outcomes were verified (all p_trend < 0.001). In the lower metabolic risk group (13,104 pairs), the association between aspirin use and HCC risk was not significant after multivariable adjustment (adjusted subdistribution hazard ratio [aSHR]: 0.93; 95% CI: 0.84–1.03); however, aspirin use was associated with elevated major bleeding risk (aSHR: 1.22; 95% CI: 1.08–1.39). In the higher metabolic risk group (2984 pairs), aspirin use was associated with reduced risks of HCC (aSHR: 0.72; 95% CI: 0.57–0.91) and liver-related mortality (aSHR: 0.69; 95% CI: 0.50–0.96) without an increase in risk of major bleeding (aSHR: 1.02; 95% CI: 0.79–1.32). Conclusions: Aspirin therapy was associated with reduced risks of HCC and liver-related death without excess risk of major bleeding, in non-cirrhotic patients with CHB who had a higher metabolic risk factor burden.