Aspirin for the prevention of hepatocellular carcinoma: an updated meta-analysis with particular focus on patients with chronic liver disease.

Background: Previous studies have suggested a chemoprotective effect of aspirin in hepatocellular carcinoma (HCC), but evidence is limited for patients with chronic liver disease (CLD). Thus, we performed a meta-analysis of all observational studies, and aimed to provide a comprehensive and quantitative understanding of this topic.

Methods: The PubMed/MEDLINE, Scopus, Cochrane, and Web of Science databases were systematically searched until September 2021. We pooled the hazard ratio (HR) of HCC for aspirin use versus non-use and investigated the possible dose-risk and duration-risk associations.

Results: Ten studies involving 202,567 CLD patients were enrolled in this study. The pooled results showed a significant reduction in HCC risk in aspirin users than in non-users (HR = 0.64; 95% CI = 0.54-0.77; p < 0.001; I = 84.9%). In subgroup analyses, an aspirin dose of 100 mg/day (0.56, 0.44-0.72) showed a significant protective effect against HCC than 160 mg/day. The linear model showed a significant inverse association between the duration of aspirin use and HCC risk (exb(b) = 0.92; 95% CI = 0.90-0.94); also, a non-linear model revealed a comparable association (coef = 0.80, p < 0.001; coef = 1.13, p = 0.001). No significantly higher risk of gastrointestinal bleeding of the aspirin-treated group was detected.

Conclusions: The present meta-analysis suggested a significant and duration-related association between reduced HCC risk and aspirin use in a broad at-risk population. Nevertheless, aspirin therapy applied to CLD patients should be carefully monitored, although there was no significantly higher risk of gastrointestinal bleeding.

Registration: PROSPERO, CRD42021229892.