Association of aspirin and statin use with the risk of liver cancer in chronic hepatitis B: A nationwide population-based study

Background & aims Aspirin and statins have been suggested to prevent hepatocellular carcinoma (HCC). However, the combined effects of aspirin and statins on HCC risk in patients with chronic hepatitis B (CHB) is not clear. Methods A nationwide nested case-control study was performed with data from the National Health Insurance Service gathered between 2005 and 2015 in Korea. In a cohort of 538,135 treatment-naive, non-cirrhotic patients with CHB, 6,539 HCC cases were matched to 26,156 controls and were analyzed by conditional logistic regression. Separate historical cohort studies for each drug were analyzed by time-dependent Cox regression as a sensitivity analysis. Results In the nested case-control study, statins (OR 0.34; 95% CI 0.32-0.37) and aspirin (OR 0.92; 95% CI 0.85-0.99) were significantly associated with a HCC risk reduction. However, dose-dependent risk reduction was observed only with statins. By sensitivity analysis in the historical cohorts, statin users (n = 244,455; HR 0.67; 95% CI 0.66-0.68) and aspirin users (n = 288,777; HR 0.81; 95% CI 0.80-0.82) had significantly lower HCC risk. In the drug-stratified analyses, statins were associated with significantly reduced risk of HCC regardless of aspirin, whereas aspirin did not show such associations. Conclusions In this nationwide population-based study of patients with CHB, statin use was consistently associated with a significant and dose-dependent reduction in HCC risk. In contrast, the association between aspirin use and HCC risk reduction was not dose-dependent and was suggested to be confounded by statins.