Immune mechanisms in drug-induced hepatotoxicity: Therapeutic implications

Abstract

Drug-induced liver injury (DILI) is a common cause of liver disease. It accounts for approximately one-half of cases of acute liver failure and significant numbers of deaths in the United States and many other countries (1-5). An estimated 1000 or more drugs have been implicated in causing liver disease on more than one occasion (5). Clinically, DILI mimics all forms of liver diseases, with the liver damage varying in severity from mild and transient increases in serum aminotransferases to fulminant hepatic failure. This represents an important diagnostic and therapeutic challenge for physicians. Idiosyncratic drug toxicity refers to toxic reactions occurring in a small subset of patients; it usually cannot be predicted during preclinical or early phases of clinical trials. The occurrence of idiosyncratic drug hepatotoxicity is also a major problem in all phases of clinical drug development and the most frequent cause of postmarketing warnings and withdrawals (1-5). DILI is usually initiated by a toxic drug and its metabolite, followed by either immune-mediated mechanisms and/or intracellular biochemical mechanisms of hepatocytes (2-5). © 2007 Humana Press Inc.