Systematic review: the hepatotoxicity of non-steroidal anti-inflammatory drugs

Aliment Pharmacol Ther. 2004 Aug 15;20(4):373-80. doi: 10.1111/j.1365-2036.2004.02092.x.


Background: Non-steroidal anti-inflammatory drugs have been implicated in reports of liver injury. However, the precise risk of non-steroidal anti-inflammatory drugs for this rare complication is unknown.

Aim: To review systematically the published literature of population-based epidemiological studies reporting the incidence or comparative risk of non-steroidal anti-inflammatory drugs for liver injury resulting in clinically significant events, defined as hospitalization or death.

Data extraction: Duplicate extraction of the methodological quality, design, source, population, years studied, particular non-steroidal anti-inflammatory drugs studied, definitions, patient counts and follow-up, and the adjustment for confounders.

Results: Seven articles met inclusion criteria. The comparative risk of liver injury resulting in hospitalization for current non-steroidal anti-inflammatory drug users compared with past non-steroidal anti-inflammatory drug users ranged from 1.2 to 1.7, but none was statistically significant. The incidence of liver injury resulting in hospitalization ranged from 3.1 to 23.4/100,000 patient-years of current use of non-steroidal anti-inflammatory drugs, with an excess risk compared with past non-steroidal anti-inflammatory drugs users of 4.8-8.6/100,000 patient-years of exposure. There were zero deaths from liver injury associated with non-steroidal anti-inflammatory drugs use in over 396,392 patient-years of cumulative exposure.

Conclusion: These findings allow for the possibility of a small increase in the risk of clinically relevant hepatotoxicity with non-steroidal anti-inflammatory drugs use, but do not document that such a risk occurs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review
  • Systematic Review

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Chemical and Drug Induced Liver Injury*
  • Hospitalization / statistics & numerical data
  • Humans
  • Liver Diseases / mortality
  • Prognosis
  • Risk Factors


  • Anti-Inflammatory Agents, Non-Steroidal