Liver failure

Acute liver failure and King's College criteria

Reviewed Nov 2026·4 references
New· views rounded down, updated weekly

Recognise ALF, find the cause, give NAC, protect the brain, support organs and use King's College criteria for transplant referral.

Definition
ALF = INR ≥ 1.5 with hepatic encephalopathy, without pre-existing cirrhosis, within 26 weeks of illness onset (EASL). Hyperacute (< 7 days jaundice-to-HE), acute (8-28 days), subacute (5-12 weeks). Hyperacute has highest cerebral oedema risk but best spontaneous survival.

At the bedside

Timed steps
  1. 1

    Confirm and grade

    0-1 h

    INR, bilirubin, glucose, lactate, ammonia, ABG, creatinine; grade HE (West Haven). Exclude cirrhosis (history, imaging).

  2. 2

    Find the cause

    Paracetamol level, viral serology (HAV IgM, HEV IgM, HBsAg/anti-HBc IgM, HSV), drugs (anti-TB drugs, herbal/ayurvedic), autoimmune, Wilson (age < 40), Budd-Chiari (Doppler), pregnancy (AFLP/HELLP), mushroom.

  3. 3

    Specific treatments

    NAC for paracetamol; NAC for early-grade non-paracetamol ALF; antivirals for HBV; delivery for AFLP/HELLP; acyclovir for HSV; steroids for autoimmune (selected).

  4. 4

    Contact a transplant centre early

    Early

    Discuss every ALF with encephalopathy or INR > 2 with a liver transplant unit; apply King's College criteria serially.

  5. 5

    Neuroprotection

    Intubate grade III-IV HE; head-up 30°, normocapnia, Na 140-150 mmol/L (hypertonic saline), treat fever; mannitol 0.5-1 g/kg or hypertonic saline for ICP surges. Ammonia > 150-200 µmol/L = high risk of cerebral oedema.

  6. 6

    Organ support

    Noradrenaline for MAP ≥ 65 mmHg after fluids; early CRRT for hyperammonaemia, AKI or fluid/acid-base problems; glucose 4-hourly (dextrose infusion for hypoglycaemia); low threshold for antibiotics/antifungals.

  7. 7

    Coagulation

    Do not correct INR prophylactically (it is a prognostic marker); vitamin K 10 mg IV once; products only for bleeding or procedures.

  8. 8

    Plasma exchange

    High-volume plasma exchange (8-12 L or 15% of ideal body weight per day for 3 days) improved transplant-free survival; consider as bridge in specialist centres.

Non-paracetamol ALF (grade I-II HE)

N-acetylcysteine

IV
Dose
150 mg/kg/h × 1 h, 12.5 mg/kg/h × 4 h, then 6.25 mg/kg/h × 67 h
Preparation
Each phase in 5% dextrose (e.g. load in 250 mL, then 500 mL, then 1,000 mL bags)
Worked example
70 kg: 10.5 g over 1 h, then 875 mg/h for 4 h, then 437.5 mg/h for 67 h
Open infusion calculator

Exclude vitamin K deficiency

Vitamin K1 (phytomenadione)

IV
Dose
10 mg slow IV once

King's College criteria (transplant referral)

AetiologyCriteria
ParacetamolArterial pH < 7.30 after fluid resuscitation, OR all of: INR > 6.5, creatinine > 3.4 mg/dL (300 µmol/L), grade III-IV HE within 24 h
Paracetamol (modified)Lactate > 3.5 mmol/L at 4 h or > 3.0 mmol/L after fluid resuscitation adds sensitivity
Non-paracetamolINR > 6.5, OR any 3 of: age < 10 or > 40 years; aetiology non-A non-B hepatitis, halothane or idiosyncratic drug reaction; jaundice-to-HE interval > 7 days; INR > 3.5; bilirubin > 17.5 mg/dL (300 µmol/L)

Low sensitivity: absence of criteria does not guarantee survival. Clichy criteria (factor V) are an alternative.

Red flag · call your senior now
Rising ammonia (> 150-200 µmol/L), grade III-IV HE, pupillary changes, hypertension with bradycardia: impending intracranial hypertension.
Red flag
Hypoglycaemia is common and can mimic worsening encephalopathy: check glucose every 1-4 h.
Pitfall
Giving FFP to 'correct' INR: masks prognosis, adds volume and rarely needed.
Pitfall
Sedating with benzodiazepines; use propofol/short-acting opioids once intubated.
Pitfall
Missing hepatitis E in pregnancy and anti-TB DILI in India.
Pearl
Sequential lactate, INR trend and HE grade guide referral better than a single value.

Calculators for this topic

Infusion rate from per-kg-per-hour dose

Pump rate for drugs dosed per kg per hour (insulin U/kg/h, midazolam mg/kg/h, propofol mg/kg/h, fentanyl mcg/kg/h, dexmedetomidine mcg/kg/h).

Glasgow Coma Scale

Eye + Verbal + Motor (3-15). Record components, e.g. E3 V4 M5.

References

  1. 1

    European Association for the Study of the Liver. EASL Clinical Practical Guidelines on the management of acute (fulminant) liver failure. J Hepatol 2017;66:1047-81.

  2. 2

    O'Grady JG, Alexander GJ, Hayllar KM, Williams R. Early indicators of prognosis in fulminant hepatic failure. Gastroenterology 1989;97:439-45.

  3. 3

    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;137:856-64.

  4. 4

    Larsen FS, Schmidt LE, Bernsmeier C, et al. High-volume plasma exchange in patients with acute liver failure: an open randomised controlled trial. J Hepatol 2016;64:69-78.

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Acute-on-chronic liver failure

Educational reference for trained clinicians. Check doses against your hospital protocol and the patient in front of you.