Abstract
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 (Ptrend = 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.
Highlights
Aspirin, because of its antiplatelet effect due to cyclooxygenase (COX) inhibition, is frequently prescribed to decrease the risk of cardiovascular disease-related mortality
There was a dose-dependent relationship between aspirin use and the risk of hepatocellular carcinoma (HCC) (P for trend = 0.002)
A well-designed, population-based cohort study, especially of a high-risk population, might be the best alternatives to address the question. In this large study with substantial duration, we found a dose-dependent association between aspirin use and the reduction of HCC risk, which was robust in the general population and in subpopulations including individuals who are young, are male, or have a history of viral hepatitis
Summary
Because of its antiplatelet effect due to cyclooxygenase (COX) inhibition, is frequently prescribed to decrease the risk of cardiovascular disease-related mortality. A few epidemiologic studies investigated the effect of aspirin on the primary prevention of HCC, but the results were inconsistent[11,12,13]. Those studies, designed to address effects of aspirin on HCC prevention, had major flaws: (i) too few HCC cases[14,15], (ii) the use of self-reporting to identify previous aspirin intake with only time point of exposure[12,13], (iii) no confirmation of dose-dependent or duration-dependent effects[12], and (iv) no consideration of potential confounders such as other putative agents (e.g., statin and metformin) and underlying liver disease (e.g., chronic viral hepatitis and/or liver cirrhosis)[12]. To clarify the relationship between aspirin use and HCC risk in Korea, we performed a cohort study of a high-risk population using nationwide pharmaceutical claims data
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