Clinical Indication of Aspirin Associated with Reduced Risk of Liver Cancer in Chronic Hepatitis B: A Nationwide Cohort Study

INTRODUCTION:Despite the overall association of aspirin on reduced hepatocellular carcinoma (HCC) risk, there have been few studies on its benefit according to specific clinical conditions among hepatitis B virus (HBV)-infected patients. This study aimed to identify subgroups which benefit from long-term aspirin use.METHODS:Nationwide data covering the HBV-infected population in the Republic of Korea from 2010 to 2011 were analyzed. Patients who had been taking Aspirin for ≥3 years were classified as aspirin users. The primary outcome was HCC development. The multivariable Fine and Gray competing risk regression model was used to estimate the adjusted hazard ratio (HR) in the entire cohort. Propensity score matching at a 1:4 ratio was also performed.RESULTS:Among 161,673 patients, 7,083 newly developed HCC during follow-up (mean: 7.5 years). After adjusting for age, sex, hypertension, diabetes mellitus, dyslipidemia, cirrhosis, antivirals, metformin, statin, smoking, alcohol consumption, and obesity, aspirin users (n = 9,837) were less likely to develop HCC; the adjusted HR was 0.84 (P = 0.002) in the entire cohort and 0.87 (P = 0.010) in the matched cohort. Association of aspirin use with all-cause mortality was not significant (HR = 0.93; P = 0.192), whereas association with liver-related mortality was significant (HR = 0.79; P = 0.019). A significant association was observed in the subgroups with cirrhosis, both sexes, hypertension, non-diabetes mellitus, nonantivirals against chronic hepatitis B, nonmetformin use, nonstatin use, both smoking histories, and obesity (all P < 0.05).DISCUSSION:Long-term aspirin use is significantly associated with reduced risk of HCC in chronic HBV patients. More comprehensive studies should be implemented to clarify the causal relationship.