ICU · gi-nutrition

Acute Liver Failure — Comprehensive (King's College Criteria, Cerebral Oedema, NAC, Transplantation)

Also known as Acute liver failure · ALF · Fulminant hepatic failure · Fulminant hepatitis · King's College criteria · Cerebral oedema in liver failure · N-acetylcysteine (NAC) · Amanita phalloides poisoning · Acute fatty liver of pregnancy · Emergency liver transplantation

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. It is a rare (incidence <10/million/year), dynamic, life-threatening syndrome whose outcome depends entirely on the cause, the speed of organ support, and the timeliness of liver-transplant referral. AETIOLOGY is the single biggest determinant of survival: PARACETAMOL overdose is the 1 cause in the UK and Australia (~40-50% of cases, mostly intentional but increasingly 'staggered'/therapeutic misadventure in the elderly); other causes are DRUG-INDUCED liver injury (DILI — isoniazid, valproate, halothane, nitrofurantoin, flavocoxid, herbal/dietary supplements), VIRAL hepatitis (hepatitis A, B [± hepatitis D superinfection], E — especially in pregnancy and immunosuppression; HSV, EBV, CMV in the immunocompromised), ISCHAEMIC hepatitis ('shock liver' following cardiac arrest or prolonged hypotension), AUTOIMMUNE hepatitis, WILSON'S disease (young patient + Coombs-negative haemolytic anaemia + low ceruloplasmin + Kayser-Fleischer rings), PREGNANCY-RELATED (acute fatty liver of pregnancy — AFLP; HELLP syndrome — third trimester/postpartum; definitive treatment is DELIVERY), MUSHROOM poisoning (Amanita phalloides — history of wild-mushroom ingestion 24-48h earlier; antidotes penicillin G + silibinin + NAC), heat stroke/malignant hyperthermia, and INDETERMINATE (~20%). The fellowship-level intensivist must master FIVE management pillars: (1) IDENTIFY AND TREAT THE CAUSE (NAC for paracetamol — and increasingly NAC for ALL causes; antivirals for viral hepatitis; corticosteroids for autoimmune; chelation for Wilson's; penicillin/silibinin for Amanita; delivery for AFLP/HELLP); (2) CEREBRAL OEDEMA — the 1 killer — ammonia crosses the blood-brain barrier, is metabolised in astrocytes to glutamine, which accumulates osmotically and causes astrocyte swelling, oedema, raised intracranial pressure and uncal herniation; high-grade (grade 3-4) encephalopathy and arterial ammonia 150 umol/L identify the at-risk brain; management = head of bed 30 degrees neutral, hypertonic saline to keep serum sodium 145-155 mmol/L, mannitol 0.5 g/kg (if ICP monitored or signs of herniation, provided serum osmolality <320), AVOID hypotension/hypoxia/hypercapnia, prophylactic intubation at grade 3, and consider hypothermia/induced coma (barbiturates) for refractory intracranial hypertension; (3) KING'S COLLEGE CRITERIA (O'Grady 1989) — the most widely used transplant-referral trigger; for PARACETAMOL ALF: arterial pH <7.25 (after fluid resuscitation, regardless of grade) OR all three of INR 6.5 + creatinine 300 umol/L + grade 3-4 encephalopathy; for NON-PARACETAMOL ALF: INR 6.5 alone OR at least 3 of (INR 3.5 + age <10 or 40 + cause non-A/non-B or drug-induced + jaundice-to-encephalopathy interval 7 days + bilirubin 300 umol/L); lactate (>3.5 at 4h or 3.0 at 12h after resuscitation) and MELD add sensitivity; (4) SUPPORT failing organs — ventilation at grade 3-4 encephalopathy (and to control PaCO2 for cerebral perfusion), noradrenaline for vasoplegic shock, CRRT (continuous, not intermittent — avoids dialysis-disequilibrium-driven ICP rise) for AKI, 10% dextrose for the universal hypoglycaemia; and (5) SURVEIL AND PREVENT INFECTION (50-80% develop bacterial infection — a leading cause of death — daily surveillance cultures, low threshold for broad-spectrum antibiotics, and antifungal cover in high-grade encephalopathy). Two critical 'do-NOT' rules: do NOT correct the INR with fresh-frozen plasma unless the patient is bleeding or undergoing a procedure — the INR is a PROGNOSTIC marker (it is the backbone of the King's College criteria) and the 'rebalanced haemostasis' of ALF means the INR does not reflect bleeding risk (viscoelastic TEG/ROTEM does); and do NOT forget that NAC benefits non-paracetamol ALF too (Lee 2009 RCT — improved transplant-free survival in early-grade, non-paracetamol ALF), so many units now give NAC to ALL ALF. Emergency liver transplantation is the definitive therapy for those who meet King's College criteria: without it mortality exceeds 80%, with it 1-year survival is approximately 80%. The intensivist's job is to REFER EARLY (transplant logistics take time), to support the brain and other organs as a BRIDGE, and to recognise the ABSOLUTE contraindications (uncontrolled sepsis, irreversible brain injury from sustained ICP 30/CPP <40, severe comorbidity, active substance misuse, uncontrolled psychiatric illness) that make transplant futile. Overall ALF mortality without transplant is 30-50% (better for paracetamol and ischaemic causes, worse for Wilson's, drug-induced, and indeterminate causes).