Drug-Induced Liver Injury in the U.S.

In 2003, the NIH established the Drug-Induced Liver Injury Network, a consortium of five academic medical centers that identifies and follows patients who develop idiosyncratic drug hepatotoxicity. In this report, the clinical features of the network’s first 300 cases are summarized. Cases of acetaminophen toxicity were excluded from this database.

The implicated substance was a single prescription medication in 73% of subjects, a dietary supplement in 9%, and more than one prescription medication (or a prescription plus a dietary supplement) in 18%. The most commonly implicated drug classes were antibiotics (46% of cases) and central nervous system agents, such as antiseizure or psychotropic drugs (15%). The most commonly implicated single agent was amoxicillin/clavulanate (23 cases); nitrofurantoin, isoniazid, and trimethoprim/sulfamethoxazole were implicated in 13 cases each. As defined by specified patterns of alanine aminotransferase and alkaline phosphatase abnormalities, 57% of cases were hepatocellular, 23% were cholestatic, and 20% were mixed. Sixty-nine percent of patients developed jaundice, 60% were hospitalized, and 8% died within 6 months. In four patients who were initially thought to have drug-induced liver injury, acute hepatitis C infection eventually was deemed responsible for the presentation.