The effects of nonsteroidal anti-inflammatory drugs in the incident and recurrent risk of hepatocellular carcinoma: a meta-analysis

Abstract

Background

Recent studies have showed that nonsteroidal anti-inflammatory drugs (NSAIDs) could reduce the risk of several types of cancer. However, epidemiological evidence of the association between NSAIDs intake and the risk of hepatocellular carcinoma (HCC) remains controversial.

Methods

To assess the preventive benefit of NSAIDs in HCC, we simultaneously searched the databases of PubMed, EmBase, Web of Science, and Scopus and screened eligible publications.

Results

A total of twelve articles (published from 2000 to 2017) from five countries were identified by retrieval. We observed a significantly lower risk of HCC incidence among users of NSAIDs than among those who did not use NSAIDs (pooled hazard ratio [HR] value =0.81, 95% confidence interval [CI]: 0.69–0.94). No evidence of publication bias was observed (Begg’s test, P=0.755; Egger’s test, P=0.564). However, when stratified according to the categories of NSAIDs, users of non-aspirin NSAIDs (HR =0.81, 95% CI: 0.70–0.94), but not aspirin (HR =0.77, 95% CI: 0.58–1.02), showed a statistically significant reduced HCC incidence. We also found that NSAIDs use significantly reduced the recurrent risk of HCC, with a HR value of 0.79 (95% CI: 0.75–0.84), whereas there was no statistically significant association between NSAIDs use and HCC mortality, with a HR value 0.65 (95% CI: 0.40–1.06).

Conclusion

Taken together, our meta-analysis demonstrates that NSAIDs significantly reduce the incident and recurrent risk of HCC.

Keywords:

• NSAIDs
• aspirin
• hepatocellular carcinoma
• incidence
• recurrence

Supplementary materials

Figure S1 Galbraith’s plot of studies that assessed the preventive effect of NSAIDs use in risk of HCC incidence.

Notes: ^*Aspirin; ^#non-aspirin NSAIDs; ^&all NSAIDs.

Abbreviations: HCC, hepatocellular carcinoma; NSAIDs, nonsteroidal anti-inflammatory drugs.

Figure S2 Forest plots of the meta-analysis on the association between NSAIDs and risk of HCC incidence after removal of the outliers of the heterogeneity.

Note: Weights are from random-effects analysis.

Abbreviations: HCC, hepatocellular carcinoma; NSAIDs, nonsteroidal anti-inflammatory drugs; HR, hazard ratio; CI, confidence interval.

Figure S3 Influence analysis of studies that assessed the effects of NSAIDs use in the risk of HCC incidence (A) and recurrence (B).

Abbreviations: HCC, hepatocellular carcinoma; NSAIDs, nonsteroidal anti-inflammatory drugs; CI, confidence interval.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (no 81600452).

Disclosure

The authors report no conflicts of interest in this work.