LiverTox: An online information resource and a site for case report submission on drug-induced liver injury.

Abstract

Drug-induced liver injury (DILI) is an infrequent cause of liver disease in the general population and accounts for< 1% of hospitalized patients presenting with jaundice. 1,2 Nonetheless, DILI is a leading reason for regulatory actions involving investigational and approved medications and is also a leading cause of acute liver failure in the United States. 3,4 Implicated drugs include not only prescription medications but also herbal products and over-the-counter dietary supplements and medications. It is noteworthy that since inception of the Drug-Induced Liver Injury Network (DILIN) by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) in 2003, the number of enrolled cases of herbal and dietary supplements-induced liver injury have steadily increased, representing the second most commonly recorded class of hepatotoxicity-causing products in DILIN. The low incidence of DILI, coupled with the limited knowledge of the biochemical mechanism(s) or pathways responsible for this ‘‘idiosyncratic’’ adverse event, make it difficult to identify high-risk patients. 5 Furthermore, preclinical testing does not always provide a reliable assessment of the hepatotoxic risk of new medications; and because DILI is a rare event, premarketing clinical studies usually conducted in highly selected populations over a relatively short period of time also may not detect a potential for liver injury. Therefore, the hepatotoxicity of a specific medication often becomes apparent only after regulatory approval—and when the drug is used by large numbers of unselected patients in the general population. Finally, because the biochemical, clinical, and histological features of DILI mimic most other known forms of acute and chronic liver injury, and there is no objective gold standard for diagnosing DILI, its identification largely relies on excluding other more common causes of liver injury and having a ‘‘compatible’’ time of onset and evolution.