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

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.

Propranolol Is Associated with Lower Risk of Incidence of Hepatocellular Carcinoma in Patients with Alcoholic Cirrhosis: A Tertiary-Center Study and Indirect Comparison with Meta-Analysis

“…For example, metformin has been reported to reduce the risk of HCC in patients with DM [35]; notably, it is also associated with tumor aggressiveness and drug resistance in advanced HCC [36,37]. Besides, long-term aspirin use lowers the risk of HCC in the general population [38]; interestingly, lack of significant chemopreventive effect in cirrhotic patients has been proposed [39]. In general practice, the effects of these medications on HCC entail more studies to be unraveled.…”

Dose and Duration of Aspirin Use to Reduce Incident Hepatocellular Carcinoma

“…In addition, use of other drugs that may have HCC preventive effects may not be fully adjusted despite the careful effort of multivariable modeling . Nevertheless, similar dose‐dependent protective effect of aspirin was recently reported in an independent Asian national cohort study, suggesting that the finding is reproducible …”

“…(4,7) Nevertheless, similar dose-dependent protective effect of aspirin was recently reported in an independent Asian national cohort study, suggesting that the finding is reproducible. (8) Despite the limitation, the study by Simon et al represents a step forward to facilitate clinical evaluation of pharmacological HCC chemoprevention strategies and warrants future follow-up studies to clarify the issues. Clinical context such as disease etiology, stage, and/or other patient characteristics can be critical to unequivocally determine the benefit and harm of aspirin, given the paradoxically increased colorectal cancer mortality when aspirin is given to the elderly.…”

Eicosanoids in carcinogenesis

“…Aspirin was shown to be effective in the precancerous adenomatosis polyposis coli or APC [152] and in terms of adenoma prior to CRC [153]. Effective aspirin use against cancers had been shown in ovarian [154,155], stomach [156][157][158], pancreas [159,160], hepatocellular carcinoma (HCC) [161], breast [162,163], prostate [164][165][166], melanoma [167] and mesothelioma [168]. Furthermore, aspirin seems to be effective in inflammatory diseases such as Alzheimer's [169] as well as in obesity, as morbid obesity increased cancer risk was reduced in those patients taking aspirin [170].…”