General aspects of drug-induced liver disease.

Medicinal agents can produce various types of hepatic injury by several mechanisms. Hepatic injury may lead to acute syndromes that resemble viral hepatitis, fatty liver of pregnancy, and obstructive jaundice, as well as to a number of chronic syndromes. Acute liver damage relates, at least in part, to the apparent mechanism of injury. Hepatic injury induced by large single overdose of intrinsically toxic drugs (e.g., acetaminophen, ferrous salts) develops within 24 to 72 hours of intake and usually is accompanied by renal failure. Regular intake of some toxic drugs, (e.g., methotrexate) leads to slowly evolving chronic disease. Liver damage due to hypersensitivity-type idiosyncrasy usually appears after 1 to 5 weeks of taking the drug unless there has been previous exposure and is preceded or accompanied by systemic features that are hallmarks of hypersensitivity. Hepatic injury attributable to metabolic idiosyncrasy may appear after weeks to months of taking the drug and usually presents without the systemic features. Organs other than the liver may be involved in the syndrome of drug-induced injury as the result of selective injury or as part of a hypersensitivity reaction.