Aspirin Use and Risk of Hepatocellular Carcinoma in a National Cohort Study of Korean Adults

The effect of aspirin on the risk of hepatocellular carcinoma (HCC) remains unclear. We investigated the association between aspirin use and HCC development in a region where viral hepatitis prevails. We conducted a population-based cohort study including a total of 460,755 participants who were tracked to identify incidents of HCC since 2007. The use of drug before the index date was assessed and standardized by the Defined Daily Dose system. We calculated the hazard ratios (HRs) and their 95% confidence intervals (CIs) for the association between aspirin use and HCC occurrence, using Cox proportional hazard regression models. There were 2,336 cases of HCC during the period of 2,965,500 person-years. Overall, aspirin users had a lower HCC risk (HR, 0.87; 95% CI, 0.77–0.98) than non-users in a dose-response manner (P(trend) = 0.002). The protective effect of aspirin was amplified when combined with those of non-aspirin non-steroidal anti-inflammatory drugs (HR, 0.65; 95% CI, 0.50–0.85). Subgroup analyses revealed a significant chemopreventive effect of aspirin in individuals who were young, were male, or had viral hepatitis, whereas no protective effect was observed in patients with liver cirrhosis. Our results, suggesting different carcinogenic pathways between viral and non-viral etiologies, may validate the design of future intervention trials of aspirin for HCC prevention in eligible populations.