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Drug-Induced Liver Injury in the U.S.

The most commonly implicated single agent was amoxicillin/clavulanate.

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.

Comment: Although the specific hepatotoxicity risk for any single drug cannot be inferred from this report, the findings provide an interesting snapshot of clinically significant drug-induced liver injury. The investigators plan to present additional analyses after enrollment of more cases in the database.

— Allan S. Brett, MD

Published in Journal Watch General Medicine January 8, 2009

Citation(s):

Chalasani N et al. for the Drug Induced Liver Injury Network (DILIN). Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States. Gastroenterology 2008 Dec; 135:1924.

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