Nonsteroidal anti-inflammatory drug-induced hepatotoxicity.

Nonsteroidal anti-inflammatory drugs are among the most common drugs associated with drug-induced liver injury, with an estimated incidence of between 3 and 23 per 100,000 patient years. Nimesulide, sulindac, and diclofenac seem to be associated with the highest risk and the only risk factor consistently identified is the concomitant use of other hepatotoxic drugs. Diclofenac-induced liver injury is a paradigm for drug-related hepatotoxicity. Recent studies suggest that genetic factors favoring the formation and accumulation of the reactive acylglucuronide metabolite of diclofenac and an enhanced immune response to the metabolite-protein adducts are associated with increased susceptibility to hepatotoxicity.