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) are 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‐naïve, non‐cirrhotic patients with CHB, 6,539 HCC cases were matched to 26,156 controls and were analysed by conditional logistic regression. Separate historical cohort studies for each drug were analysed 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.