Drug-induced liver disorders - Implications for drug development and regulation

Drug-induced hepatotoxicity is a frequent cause of liver disease. Although often presenting as acute hepatitis and/or cholestasis, virtually any clini cal-pathological pattern of acute or chronic liver disease can occur. Most reactions occur in a small proportion of the population using a particular drug. Each drug associated with hepatotoxicity tends to have a characterist ic signature regarding latency and pattern of injury. The mechanism can be drug metabolism-dependent or related to the chemical properties of the pare nt drug. The former are immune mediated or due to metabolic idiosyncrasy. M onitoring serum ALT levels is of unproven effectiveness but should be consi dered when there is an increased risk of delayed onset serious hepatitis-li ke reactions. The key for the future is improved identification of toxic po tential in preclinical studies, clinical trials and postmarketing experienc e. The elucidation of the genetic and environmental mechanisms contributing to delayed idiosyncratic reactions is a major barrier to overcome in this field.