Clinical aspects of drug-induced hepatitis

The drug reactions of the liver may be classified as to (1) reproducibility, (2) severity, (3) localization and (4) duration of the lesion. Ad 1) Few drugs give a reproducible, dose dependent, hepatic reaction (e.g. acetaminophen), a greater problem is the unpredictable, dose independent reactions caused by "indirect" hepatotoxic drugs (e.g. imipramin). Ad 2) Drug reactions may be fatal (e.g. halothane), of limited clinical importance (e.g. clorpromazin) or clinically insignificant (e.g. iopanoic acid). Ad 3) Histologically, and to some extent clinically, hepatocellular (e.g. propylthiouracil) may be distinguished from cholestatic (e.g. tolbutamide) reactions, but overlapping (e.g. phenylbutazone) and individual variations are common. Ad 4) Most drug reactions are acute, but an insiduous course, developping to cirrhosis, is increasingly recognized (e.g. oxyphenacetin). Drug reactions are usually not clinically, biochemically and morphologically distinct from other common liver diseases and are only diagnosed if this possibility is constantly kept in mind. Treatment other than withdrawal of suspected or known etiologic agents is virtually lacking. The basis for prophylaxis is careful registration of all drug reactions. Potentially hepatotoxic drugs should only be administered after thorough cost/benefit considerations.