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

Summary 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.