, Volume 16, Issue 1, pp 25–45 | Cite as

Drug-Induced Liver Disease

  • Hyman J. Zimmerman
Review Article


The large number of chemical agents administered for therapeutic or diagnostic purposes can produce various types of hepatic injury by several mechanisms. Acute injury may be cytotoxic, cholestatic or mixed. Cytotoxic injury may consist of necrosis or steatosis. Cholestatic injury may be cholangiolitic (hepatocanalicular) or bland (canalicular). Chronic hepatic lesions caused by medicinal agents include chronic active hepatitis, steatosis, cirrhosis, fibrosis, hepatoportal sclerosis (non-cirrhotic portal hypertension), hepatic vein thrombosis, peliosis hepatis, adenoma, carcinoma, and angiosarcoma. There is a useful relationship between the type of hepatic injury and the chemical setting in which the drugs are employed.

Some agents produce the liver damage because they are intrinsic (true, predictable) hepatotoxins. Others (non-predictable ‘hepatotoxins’), produce hepatic injury only in the rare and unusually susceptible individual (idiosyncratic injury). Hepatotoxic agents can be recognised by their dose-dependent and experimental reproducibility, properties which are not shared by agents which produce hepatic injury only in idiosyncratic hosts.

Intrinsic hepatotoxins may be categorised as direct or indirect. Direct hepatotoxins injure the hepatocyte by direct physiochemical alteration and as a consequence produce metabolic defects. Indirect hepatotoxins selectively block metabolic pathways and, by producing a precise biochemical lesion, lead to structural changes. They may lead to hepatic steatosis or necrosis (cytotoxic indirect hepatotoxins) or block bile flow (cholestatic indirect hepatotoxins). Direct hepatotoxins are rarely encountered as drugs.

Overdoses of some drugs and antineoplastic agents appear to be indirect cytotoxic hepatotoxins, and the C-17 alkylated anabolic and contraceptive steroids are indirect, cholestatic hepatotoxins. Idiosyncracy of the host is the mechanism for most types of drug-induced hepatic injury. It may reflect allergy to the drug or a metabolic aberration of the host permitting the production of hepatotoxic metabolites.


Halothane Hepatic Injury Phenylbutazone Contraceptive Steroid Iproniazid 
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Copyright information

© ADIS Press 1978

Authors and Affiliations

  • Hyman J. Zimmerman
    • 1
  1. 1.Medical ServiceVeterans Administration Hospital and George Washington University School of MedicineWashington DCUSA

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