Acute episode of severe liver dysfunction (jaundice, encephalopathy, coagulopathy) in a patient with a previously normal liver

Aetiology

• Paracetamol - accounts for 50% of cases in the UK
• Antibiotics
• Viral - Hep. A-E, CMV, EBV, toxoplasmosis
• Rare causes - AFLP, mushrooms, malignancy, Wilson’s, Budd Chiari, HAV

Pathophysiology

Paracetamol overdose

• Accidental or non-accidental
• Highly toxic intermediate (NAPQI) produced in paracetamol metabolism is normally immediately inactivated by glutathione
• Toxicity can occur in normal doses if:
  • Patient has reduced glutathione stores (e.g. in anorexia)
  • Paracetamol has a longer half-life
  • Patient has increased P4502E1 (e.g. due to alcoholism) - bioactivate paracetamol to form toxins

Clinical features

• Jaundice
• Nausea
• Stomach pain
• Encephalopathy

Investigations

• Bloods:
  • LFTs: ALT/AST > ALP, ↑ bilirubin, ↓ albumin
  • Hy’s rule (marker of severity for DILI) - if patient has ALT/AST >5x upper limit of normal AND bilirubin >3mg/dl they are at high risk of death/liver transplant
  • ↑ prothrombin time
  • Virology
• USS
• Rarely liver biopsy