Core63: Drug-induced adverse reaction: hepatotoxicity

🫀 High-yield / 要点：Drug-induced liver injury (DILI) is classified as hepatocellular, cholestatic, or mixed. It can be predictable dose-dependent or idiosyncratic.

Definition / 定義

• Hepatotoxicity / DILI = drug-induced liver injury.
• Can present as acute liver injury.
• Mechanistically:
  • Predictable = dose-dependent.
  • Unpredictable = idiosyncratic.

Clinical types / 臨床分類

Type	Laboratory pattern	Examples
Hepatocellular	ALT ≥ 5× normal	Paracetamol, NSAIDs, INH, rifampicin, pyrazinamide, halothane, valproic acid, amiodarone
Cholestatic	ALP ≥ 2× normal	Oral contraceptives, amoxicillin-clavulanate, anabolic steroids, chlorpromazine, fibrates
Mixed	ALT ≥ 3× normal and ALP ≥ 2× normal	Statins, reverse transcriptase inhibitors, nitrofurantoin, phenytoin

Important examples / 重要例

• Hepatocellular injury:
  • Paracetamol.
  • NSAIDs.
  • Anti-tuberculotics: INH, rifampicin, pyrazinamide.
  • Halothane.
  • Valproic acid.
  • Amiodarone.
• Cholestatic injury:
  • Oral contraceptives.
  • Amoxicillin-clavulanate.
  • Anabolic steroids.
  • Chlorpromazine.
  • Fibrates.
• Mixed injury:
  • Statins.
  • Reverse transcriptase inhibitors.
  • Nitrofurantoin.
  • Phenytoin.

Treatment / 治療

• Stop the causative drug.
• N-acetylcysteine:
  • Increases glutathione stores.
  • Reduces oxidative damage.
• In cholestasis:
  • Ursodeoxycholic acid reduces toxicity of hydrophobic bile acids on membranes.
• Severe acute liver injury:
  • Definitive therapy = liver transplantation.

Remember / 覚え方

• Paracetamol = classic hepatocellular injury
• Amoxiclav = classic cholestatic injury
• Statins/nitrofurantoin/phenytoin = mixed pattern
• N-acetylcysteine is the classic antidote for acute toxic liver injury