• Types
  • Direct Hepatotoxins with Intrinsic Reaction (Onset within 48 hours)
  1. Background
    1. Predictable, dose-dependent injury
    2. Biopsy (if performed) shows necrosis at terminal hepatic venule
  2. Causes
    1. See Hepatotoxin
    2. Carbon tetrachloride
    3. Benzene derivative
    4. Mushroom Poisoning
    5. Herbal Toxicity
    6. Antiepileptics
    7. Amiodarone
    8. Methotrexate
    9. Acetaminophen (42% of acute liver injury in U.S.)
      1. See Acetaminophen Toxicity
    10. Antibiotics (second most common cause in U.S.)
      1. Amoxicillin-clavulanate
      2. Trimethoprim-sulfamethoxazole
      3. Isoniazid
      4. Nitrofurantoin
  • Types
  • Idiosyncratic Reaction (Variable onset)
  1. Background
    1. Often not dose-dependent
    2. Variable timing (may occur over days or months)
    3. Transaminases improve within weeks after drug cessation
      1. However, full transaminase normalization may take 2-3 months after stopping causative agent
      2. Transaminase resolution after drug cessation is sufficient for diagnosis (liver biopsy not needed)
  2. Signs
    1. Fever
    2. Rash
    3. Arthralgia
    4. Eosinophilia
  3. Causes
    1. Isoniazid
    2. Halothane
    3. Phenytoin
    4. Methyldopa
  • Resources