Acute liver failure: cerebral oedema, King's College criteria, and transplantation

Also known as Acute liver failure · ALF · Fulminant hepatic failure · Fulminant hepatitis · King's College criteria

Acute liver failure (ALF) = severe acute liver injury with encephalopathy + coagulopathy (INR ≥1.5) within 26 weeks of symptom onset, in a patient WITHOUT pre-existing liver disease. CAUSES: paracetamol overdose (1 — 40%), drug-induced (idiosyncratic — isoniazid, valproate, halothane), viral (hepatitis A/B/E — especially if immunosuppressed), ischaemic ('shock liver' — from hypotension), autoimmune, Wilson's disease, pregnancy (AFLP, HELLP), mushroom (Amanita phalloides), indeterminate (20%). CLINICAL: jaundice, encephalopathy (confusion → coma), coagulopathy (bleeding), hypoglycaemia, infection, AKI, haemodynamics (hyperdynamic → shock). CEREBRAL OEDEMA is the 1 killer (especially in high-grade encephalopathy + hyperammonaemia 150). KING'S COLLEGE CRITERIA predict mortality → transplant referral. MANAGEMENT: TREAT CAUSE (NAC for paracetamol; antivirals; steroids for autoimmune; penicillin for mushrooms); SUPPORT organs (ventilation, vasopressors, RRT); CEREBRAL OEDEMA (head elevation 30°, hypertonic saline/mannitol, hyperventilation bridge, ICP monitoring for grade 3-4); COAGULOPATHY (only bleed if transfuse — 'rebalanced haemostasis'); INFECTION PROPHYLAXIS (antibiotics + antifungals — infection is common + often triggers deterioration); HYPOGLYCAEMIA (10% dextrose infusion — liver can't gluconeogenesis). LIVER TRANSPLANT = definitive for those meeting King's College criteria. MORTALITY: 30-50% without transplant; 20% with transplant.

high13 referencesUpdated 26 July 202611 min readVerification in progress

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8 MCQs

The one-line answer

Acute liver failure (ALF) is severe acute liver injury with encephalopathy and coagulopathy (INR at least 1.5) within 26 weeks of onset, in a patient without pre-existing liver disease (US ALFSG definition). Cerebral oedema is the number-one killer — it tracks encephalopathy grade and arterial ammonia, and it is the death you can prevent with disciplined neuroprotection.^[5]

Treat the cause (N-acetylcysteine for paracetamol, and considered in grade 1 to 2 non-paracetamol ALF), support the organs (ventilation, vasopressors, CRRT, 10 percent dextrose for hypoglycaemia, infection prophylaxis), apply King's College criteria early and repeatedly to trigger transplant referral, and protect the brain: head up 30 degrees neutral, hypertonic saline to a sodium of 145 to 155, normocapnia, and normoglycaemia.^[9]^[2]

Meet the patient

Cushing's response. A 28-year-old is day 3 into a paracetamol overdose — INR 6.2, arterial ammonia 185, sodium 137, intubated this morning for grade 3 encephalopathy — when blood pressure reaches 204 over 112, heart rate 44, and the right pupil is 5 mm and sluggish.^[2]

That triad — hypertension, bradycardia, and an unequal pupil — is Cushing's response, a late pre-terminal sign of uncal herniation. Management now turns on whether intracranial pressure can be dropped before the brainstem is lost, and whether the King's College criteria are already met for transplant.^[9]

References13Show

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[10]Pan JJ, Fontana RJ CAQ Corner: Acute liver failure management and liver transplantation Liver Transpl, 2022.PMID 35574981
[11]McPhail MJ, Farne H, Senvar N, et al. Ability of King's College Criteria and Model for End-Stage Liver Disease Scores to Predict Mortality of Patients With Acute Liver Failure: A Meta-analysis Clin Gastroenterol Hepatol, 2016.PMID 26499930
[12]Jothimani D, Marannan NK, Rela M Acute liver failure and liver transplantation Indian J Gastroenterol, 2025.PMID 39964603
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