Regular Aspirin Use Is Associated with a Reduced Risk of Hepatocellular Carcinoma (HCC) in Chronic Liver Disease: a Systematic Review and Meta-analysis

Purpose: Aspirin reduces the incidence of various gastrointestinal (GI) malignancies. This meta-analysis assessed the efficacy and safety of regular aspirin use on the incidence of hepatocellular carcinoma (HCC) in patients with chronic liver disease. 

Methods: Electronic reference databases were searched for studies in patients with chronic liver disease exposed to aspirin. The primary outcome was the incidence of HCC in regular aspirin users compared to non-users. The secondary outcome was the incidence of major GI bleeding events in both groups. The propensity score (PS) and non-PS-adjusted pooled hazard ratio (HR) were calculated using random-effects models. 

Results: Six observational studies with 71,211 subjects were included. The median duration of follow-up ranged from 2.7 to 7.9 years. Four studies included patients with viral hepatitis; five studies used aspirin 100 mg/day. All six studies reported the non-PS-matched HR, and there was a 54% reduction in the incidence of HCC among regular aspirin users [HR (95% CI): 0.46(0.31–0.67), p < 0.001]. Four studies reported on the PS-matched HR; this showed a 46% reduced incidence of HCC in those using aspirin [HR (95% CI): 0.54(0.38–0.79), p < 0.001]. Subgroup analysis on studies restricted to viral hepatitis (n = 4) showed a 28% reduction in HCC incidence in aspirin users [HR (95% CI): 0.72(0.64–0.80), p < 0.001]. Four studies reported the incidence of major GI bleeds, there was no significant difference between the two groups [HR (95% CI: 1.00(0.69–1.45), p = 0.90]. All outcome analysis, except the subgroup analysis, had significant inter-study heterogeneity. 

Conclusion: Regular aspirin use in chronic liver disease is associated with reduced incidence of HCC without increasing the risk of major GI bleeding.