The mechanisms are variable, complex, and, in most instances, poorly understood. No classification of liver damage caused by drugs is completely satisfactory. Some drugs can produce chronic damage, including tumors. Mild jaundice can occur from drug-induced hemolysis with unconjugated hyperbilirubinemia, but no true hepatic damage occurs and liver function tests are normal. Liver damage is often not apparent until 2 to 5 days after ingestion of acetaminophen, when clinical and biochemical evidence of acute hepatocellular necrosis develops.
Evidence also incriminates acetaminophen in chronic liver damage.
Offending agents are numerous and include isoniazid, methyldopa, monoamine oxidase inhibitors, indomethacin, propylthiouracil, phenytoin, diclofenac, and the anesthetic halothane. Of these, isoniazid and halothane have been most thoroughly studied. Unlike most cases of drug-related hepatitis, which appear within a few weeks of starting the drug, injury caused by isoniazid may be delayed up to 1 year, and by then the association may be overlooked. Unless the drug is stopped, progressive chronic hepatitis and cirrhosis can develop. Whether the reaction is caused by a hypersensitivity mechanism or by hepatotoxic metabolites is uncertain, but most evidence favors the latter.