ACUTE LIVER-INJURY ASSOCIATED WITH NONSTEROIDAL ANTIINFLAMMATORY DRUGS AND THE ROLE OF RISK-FACTORS

Background: Hospitalizations for acute liver injury in the absence of a viral infection or ally other well-defined pathologic finding that c ould have caused it is rare. In this study, we included both outpatien ts and hospitalized patients with acute liver injury to estimate the r isk of clinically important acute liver injury associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and to study the rol e of certain risk factors. Methods: This was a retrospective cohort st udy with secondary case-control analysis. The study included 536 gener al practitioners' practices in England and Wales for the period Octobe r 1987 through August 1991. A total of 625 307 persons who received mo re than 2 million prescriptions for one of 12 NSAIDs were followed up to estimate the risk of newly diagnosed acute liver injury. Results: T here were 23 cases of acute liver injury. The incidence of acute liver injury was 3.7 per 100 000 NSAID users or 1.1 per 100 000 NSAID presc riptions. None of the cases had a fatal outcome. Sulindac was the only NSAID with a substantially greater risk than that for the overall NSA ID group. Users of NSAIDs who had rheumatoid arthritis had a 10-fold i ncreased risk of acute liver injury compared with NSAID-treated patien ts with osteoarthritis. Concomitant exposure to other hepatotoxic medi cations also increased the risk. Transient minor increases in liver te st values were not a useful predictor of diagnosed NSAID-associated ac ute liver injury. Conclusions: Although NSAIDs have been found to be a ssociated with acute liver injury in a small number of persons, the ri sk is sufficiently small as to be of minimal concern for most NSAIDs.