DOSE-DEPENDENT (DIRECT HEPATOTOXINS)

Onset is within 48 h, predictable, necrosis around terminal hepatic venule—e.g., carbon tetrachloride, benzene derivatives, mushroom poisoning, acetaminophen, or microvesicular steatosis (e.g., tetracyclines, valproic acid).

IDIOSYNCRATIC

Variable dose and time of onset; small number of exposed persons affected; may be associated with fever, rash, arthralgias, eosinophilia. In many cases, mechanism may actually involve toxic metabolite, possibly determined on genetic basis—e.g., isoniazid, halothane, phenytoin, methyldopa, carbamazepine, diclofenac, oxacillin, sulfonamides.

Treatment: Toxic and Drug-Induced Hepatitis

Supportive as for viral hepatitis; withdraw suspected agent, and include use of gastric lavage and oral administration of charcoal or cholestyramine. Liver transplantation if necessary. In acetaminophen overdose, more specific therapy is available in the form of sulfhydryl compounds (e.g., N-acetylcysteine). These agents appear to act by providing a reservoir of sulfhydryl groups to bind the toxic metabolites or by stimulating synthesis of hepatic glutathione. Therapy should be begun within 8 h of ingestion but may be effective even if given as late as 24–36 h after overdose.

Outline

• Acute Hepatitis
  • VIRAL HEPATITIS
  • TOXIC AND DRUG-INDUCED HEPATITIS
  • FULMINANT HEPATITIS