Expansion
Hepatocellular, cholestatic or mixed; intrinsic or idiosyncratic
Expansion
Two mechanisms
- Intrinsic, dose dependent and predictable: paracetamol, the commonest cause of acute liver failure in the UK
- Idiosyncratic, not dose related, unpredictable, days to months after starting: co-amoxiclav, flucloxacillin, isoniazid and most others
Three patterns, defined by the enzyme ratio
- Hepatocellular, ALT dominant: paracetamol, isoniazid, methotrexate, statins, valproate, halothane, NSAIDs
- Cholestatic, ALP dominant: co-amoxiclav, flucloxacillin, anabolic steroids, the combined oral contraceptive, chlorpromazine, erythromycin
- Mixed
“Co-amoxiclav and flucloxacillin cause cholestasis weeks after the course has finished”, which is why the drug history must reach back months and why patients often deny recent medication.
Hy’s law: ALT over 3 times normal with bilirubin over 2 times normal and no biliary obstruction predicts a mortality of around 10 per cent.
Management: stop the drug, supportive care, N-acetylcysteine for paracetamol, and consider transplant referral using the King’s College criteria. Report through the Yellow Card scheme and record the reaction so the drug is avoided permanently.