Daily aspirin associated with a reduced risk of hepatocellular carcinoma in patients with non-alcoholic fatty liver disease: a population-based cohort study

Background: Emerging laboratory and animal studies suggest that aspirin may prevent non-alcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma (HCC), however clinical evidence remains lacking. Methods: Using Taiwan's National Health Insurance Research Database, we screened 145,212 NAFLD patients from 1997 through 2011. After excluding any confounding conditions, 33,484 patients who continuously received a daily dose of aspirin for 90 days or more (treated group), along with 55,543 patients who had not received antiplatelet therapy (untreated group), were respectively recruited. Inverse probability of treatment weighting using the propensity score was applied to balance the baseline characteristics. Cumulative incidence of, and hazard ratio (HR) for HCC occurrence were analyzed after adjusting competing events. The high-risk patients, who were defined as age ≥ 55 years & elevated serum alanine aminotransferase, were further analyzed. Findings: The 10-year cumulative incidence of HCC in the treated group was significantly lower than that in the untreated group (0.25% [95% CI, 0.19–0.32%] vs. 0.67% [95% CI, 0.54–0.81%]; P < 0.001). Aspirin therapy was significantly associated with a reduced HCC risk (adjusted HR [aHR] 0.48 [95% CI, 0.37–0.63]; P < 0.001). In the high-risk patients, the 10-year cumulative incidence of HCC in the treated group was significantly lower than that in the untreated group (3.59% [95% CI, 2.99–4.19%] vs. 6.54% [95% CI, 5.65–7.42%]; P < 0.001). Aspirin therapy remained associated with a reduced HCC risk (aHR 0.63 [95% CI, 0.53–0.76]; P < 0.001). Subgroup sensitivity analyses verified this significant association in nearly all subgroups. In the time-varying model amongst aspirin users, HCC risk was significantly lower through the use of aspirin for ≥ 3 years (aHR 0.64 [95% CI, 0.44–0.91]; P = 0.013), when compared with short-term use (< 1 year). Interpretation: Daily aspirin therapy is significantly associated with a reduced HCC risk in NAFLD patients. Funding: Ministry of Science and Technology, Ministry of Health and Welfare, and Taichung Veterans General Hospital, Taiwan.