Nonsteroidal anti-inflammatory drugs, especially aspirin, are linked to lower risk and better survival of hepatocellular carcinoma: a meta-analysis

Objective: The roles of nonsteroidal anti-inflammatory drugs (NSAIDs) in the occurrence and prognosis of hepatocellular carcinoma (HCC) remain controversial. This analysis aimed to summarize the relationships between NSAIDs and HCC development. Methods: Studies published prior to October 1, 2017, in the PubMed, Embase, Ovid, Web of Science, and Cochrane Library databases were systematically searched and analyzed. Results: Eleven studies were included in this analysis. A meta-analysis of five studies revealed that aspirin use could significantly decrease the risk of HCC occurrence (hazards ratio [HR] = 0.64, 95% confidence interval [CI] = 0.45-0.91, P = 0.014). No significant difference was found for the use of NSAIDs (six studies) and non-aspirin NSAIDs (three studies) in HCC occurrence (HR = 0.74, 95% CI = 0.53-1.02, P = 0.064 and HR = 0.98, 95% CI = 0.87-1.12, P = 0.81, respectively). However, subgroup analysis of cohort studies demonstrated that NSAIDs significantly decreased the risk of HCC occurrence (HR = 0.58, 95% CI = 0.43-0.78, P < 0.001). HCC patients who received NSAIDs achieved better disease-free survival and overall survival compared with the non-NSAID users (HR = 0.79, 95% CI = 0.74-0.84, P< 0.001 and HR = 0.60, 95% CI = 0.50-0.72, P< 0.001, respectively). Additionally, a meta-analysis of two studies showed that aspirin treatment in HCC patients could significantly decrease the 2-year and 4-year mortalities (rate ratio [RR] = 0.50, 95% CI = 0.36-0.69, P < 0.001 and RR = 0.67, 95% CI = 0.45-0.998, P = 0.049, respectively). A meta-analysis of two studies showed that aspirin use was not associated with a higher risk of bleeding in HCC patients (HR = 0.71, 95% CI = 0.41-1.23, P = 0.223). Conclusion: The use of NSAIDs, especially aspirin, is linked to a lower risk of HCC development and better survival in HCC populations. High-quality, well-designed trials should be conducted to reevaluate the relationships between NSAIDs and HCC.