Phys · hepatic
Acute Liver Failure
Also known as fulminant hepatic failure · fulminant liver failure · acute hepatic failure · subacute liver failure · hyperacute liver failure · King's College Criteria · ceruloplasmin · hepatic encephalopathy
Consultant-physician-depth guide to acute liver failure — the definition (encephalopathy and coagulopathy within 26 weeks, without pre-existing liver disease), the causes by category (paracetamol, idiosyncratic drug, viral, autoimmune, Wilson disease, ischaemic, Budd-Chiari, pregnancy-related, mushroom poisoning), the King's College Criteria for transplant (paracetamol versus non-paracetamol), the full ICU management algorithm, and the complications with cerebral oedema as the leading cause of death. Structured for FRACP DWE and DCE preparation.
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Red flags
- Encephalopathy with INR above 1.5 within 26 weeks, without prior liver disease — the definition of acute liver failure
- Grade 3 to 4 encephalopathy — risk of cerebral oedema, the leading cause of death
- Cushing reflex (hypertension with bradycardia) — intracranial hypertension, impending herniation
- Young patient with Coombs-negative haemolysis and low ALP — Wilson disease, near-universal mortality without transplant
- Arterial pH below 7.3 in paracetamol ALF — meets King's College Criteria alone, urgent transplant referral
- Arterial lactate above 3.5 mmol/L on admission — early predictor of non-survival, refer early
- Hypoglycaemia — both a complication and a poor prognostic sign
Acute Liver Failure
The answer first
Acute liver failure is severe acute liver injury with coagulopathy (INR above 1.5) and encephalopathy, developing within 26 weeks of symptom onset, in a patient without pre-existing liver disease. Every word of that definition earns its place. The coagulopathy and the encephalopathy are the two mandatory criteria — a patient with jaundice and ALT of 3000 but a normal INR and normal mentation has acute severe hepatitis, not acute liver failure (ALF). The 26-week boundary separates ALF from chronic and subacute presentations. And the absence of pre-existing liver disease is essential, because acute decompensation of cirrhosis runs a different course and a different management pathway. [1]
The single organising principle for the whole topic: ALF is a time-critical emergency in which the cause determines the specific treatment, the King's College Criteria determine the transplant decision, and cerebral oedema is the leading cause of death. Everything else is detail hung on those three hooks. [1]
Know the causes table cold. It is the highest-yield page in ALF and answers most aetiology MCQ stems at a glance. [1]
| Cause | Key clue | Specific treatment | Prognosis (transplant-free) |
|---|---|---|---|
| Paracetamol | Overdose history, level, high AST/ALT | N-acetylcysteine | Best (over 60 percent) |
| Idiosyncratic drug | Onset days to weeks after new drug | Stop the drug, NAC empirically | Poor |
| Viral (HAV, HBV, HEV) | Serology, travel, pregnancy (HEV) | Supportive, antiviral for HBV | Moderate |
| Autoimmune | ANA, SMA, high IgG | Corticosteroids (selected) | Moderate |
| Wilson disease | Young, haemolysis, low ALP | Chelation, urgent transplant | Worst (near 100 percent medical mortality) |
| Ischaemic (shock liver) | Hypotension, cardiac arrest | Restore perfusion | Good if perfusion restored |
| Budd-Chiari | Ascites, hepatomegaly, thrombosis | Anticoagulation, transplant | Variable |
| Pregnancy-related (AFLP, HELLP) | Third trimester, hypertension | Deliver the baby | Good after delivery |
| Mushroom (Amanita phalloides) | Foraging history, GI prodrome | Penicillin G, silibinin | Variable |
DWE high-yield: In the West, paracetamol is the most common cause of ALF. In the developing world, viral hepatitis (especially HEV) dominates. The US ALFSG cohort (Ostapowicz, 308 patients) found paracetamol in 39 percent, idiosyncratic drugs in 13 percent, and hepatitis A and B together in only 12 percent [3]. This is the aetiological landscape an examiner expects you to know.
References9ShowHide
- [1]O'Grady JG, Alexander GJM, Hayllar KM, Williams R Early indicators of prognosis in fulminant hepatic failure Gastroenterology, 1989.PMID 2490426
- [2]Lee WM Acute liver failure N Engl J Med, 1993.PMID 8305063
- [3]Ostapowicz G, Fontana RJ, Schiødt FV, et al. Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States Ann Intern Med, 2002.PMID 12484709
- [4]Bernal W, Donaldson N, Wyncoll D, Wendon J Blood lactate as an early predictor of outcome in paracetamol-induced acute liver failure: a cohort study Lancet, 2002.PMID 11867109
- [5]Keays R, Harrison PM, Wendon JA, et al. Intravenous acetylcysteine in paracetamol induced fulminant hepatic failure: a prospective controlled trial BMJ, 1991.PMID 1954453
- [6]Lee WM, Hynan LS, Rossaro L, et al. Intravenous N-acetylcysteine improves transplant-free survival in early stage non-acetaminophen acute liver failure Gastroenterology, 2009.PMID 19524577
- [7]Stravitz RT, Lee WM Acute liver failure Lancet, 2019.PMID 31498101
- [8]Bernal W, Wendon J Acute liver failure N Engl J Med, 2013.PMID 24369077
- [9]Tujios SR, Stravitz RT, Lee WM Management of Acute Liver Failure: Update 2022 Semin Liver Dis, 2022.PMID 36001996