Liver emergencies

Acute liver failure

Overview and approach

Acute liver failure involves acute liver injury with coagulopathy and encephalopathy without established cirrhosis.

  • Definition (EASL): severe acute liver injury (marked aminotransferase rise, jaundice and coagulopathy, usually INR >1.5) plus hepatic encephalopathy, in a patient without pre-existing chronic liver disease (2).
    • Exception: acute presentations of autoimmune hepatitis, Wilson disease and Budd–Chiari count as ALF if encephalopathy develops, even with underlying liver disease (2).
  • Sub-classification by jaundice-to-encephalopathy interval (O'Grady): hyperacute <1 week, acute 1–4 weeks, subacute 4–12 weeks (2).
    • Hyperacute (e.g. paracetamol): worst coagulopathy and highest risk of intracranial hypertension, but best chance of spontaneous survival. Subacute: deeper jaundice, less cerebral oedema, worst transplant-free survival (2).
  • Approach: exclude cirrhosis/alcohol-related injury/malignant infiltration, find the cause, screen intensively for encephalopathy, and start early discussion with a liver transplant unit even before the patient meets criteria (2).
Assessment and clinical features

Assess mental state, glucose, toxin/drug history, pregnancy and perfusion.

  • Common causes: paracetamol, other drugs, viral hepatitis (see Viral hepatitis page), autoimmune hepatitis, Wilson disease, ischaemia, pregnancy-related liver disease.
  • History: full drug list including over-the-counter, herbal and supplements; paracetamol timing and formulation (immediate vs modified release); mushroom ingestion; travel (HBV/HEV); pregnancy; autoimmune disease (2).
  • Clues to specific causes (2):
    • Wilson disease: young patient, Coombs-negative haemolytic anaemia, high bilirubin to ALP ratio.
    • Acute Budd–Chiari: ALF with gross ascites; diagnose on imaging.
    • HELLP / acute fatty liver of pregnancy: late pregnancy; treatment is prompt delivery.
    • Autoimmune: other autoimmune conditions, raised globulins, autoantibodies (may be absent).
    • Hypoxic hepatitis: very high aminotransferases with high LDH and creatinine after shock.
  • Encephalopathy grading: use West Haven grades 1–4 (see Hepatic encephalopathy page); in ALF even subtle confusion (grade 1–2) is significant and can progress within hours (2)(5).
  • Monitor: SpO2, BP, HR, RR, hourly urine output, neuro obs, BGL (2).
Differentials and investigations

Use urgent liver/renal/coagulation, toxin/viral tests and specialist-directed imaging.

  • Liver function, INR, glucose, lactate, venous gas, renal function, paracetamol level, viral serology, autoimmune and copper studies as indicated; ultrasound with Doppler.
  • EASL admission work-up (2):
    • Bloods: FBC, INR/PT (± factor V), LFTs incl. LDH and conjugated bilirubin, CK, U&E, glucose, phosphate, Mg, Ca, amylase/lipase, arterial lactate and arterial ammonia, ABG, blood group.
    • Toxicology: paracetamol level, urine drug screen.
    • Viral: HAV IgM, HBsAg + anti-HBc IgM (HBV DNA; HDV if HBV positive), HEV, HSV and VZV IgM/PCR, CMV, EBV.
    • Autoimmune markers, immunoglobulins; caeruloplasmin/copper and haemolysis screen if Wilson possible; β-hCG.
    • Cultures (blood, urine, sputum), CXR, ECG; liver ultrasound with Doppler (hepatic and portal veins); cross-sectional imaging if needed.
  • Differentials: acute-on-chronic liver failure / decompensated cirrhosis (different pathway; see Cirrhosis page), sepsis with cholestasis, severe alcohol-related hepatitis, malignant infiltration (2).
  • Paracetamol: the treatment nomogram was unchanged in the 2020 ANZ guidelines; modified-release ingestions ≥10 g or ≥200 mg/kg (whichever is less) get a full NAC course (3). See the guideline's flowcharts for staggered, repeated supratherapeutic and unknown-time ingestions.
Management and follow-up

Provide immediate hepatology/transplant-centre and ICU discussion, supportive care and cause-specific treatment.

  • Early discussion with a liver transplant centre and ICU; cause-specific antidote or antiviral where applicable.
  • Paracetamol – IV acetylcysteine, ANZ two-bag regimen (3):
    • Bag 1: 200 mg/kg over 4 h (max 22 g); Bag 2: 100 mg/kg over 16 h (max 11 g). Adults dosed on actual weight rounded up to nearest 10 kg, capped at 110 kg.
    • Paracetamol concentration >2x nomogram line: bag 2 doubled to 200 mg/kg over 16 h; ≥3x line: discuss higher doses with a clinical toxicologist / Poisons Information Centre.
    • Near end of infusion: repeat ALT (± paracetamol). Continue at the bag 2 rate if paracetamol >10 mg/L (66 µmol/L) or ALT raised and rising; stop only when ALT/AST falling, INR <2.0 and patient clinically well (3).
    • Activated charcoal 50 g if awake and cooperative within 2 h of a toxic immediate-release dose (4 h if >30 g or modified release) (3).
  • Non-paracetamol ALF – IV NAC: EASL advises NAC in early-stage ALF even when not caused by paracetamol (2). The trial regimen (Lee 2009) was 150 mg/kg over 1 h, then 12.5 mg/kg/h for 4 h, then 6.25 mg/kg/h for 67 h (72 h total); transplant-free survival improved only in coma grade I–II (52% vs 30%), not grade III–IV (4). Many Australian units use the paracetamol regimen; follow the local protocol.
  • Supportive care (EASL) (2):
    • Avoid sedatives and hepatotoxic/nephrotoxic drugs. Stress ulcer prophylaxis.
    • Glucose infusion (10–20%); check BGL frequently. Hypoglycaemia is common and linked to mortality.
    • Keep Na 140–150 mmol/L; correct phosphate, Mg and K. Renal replacement therapy for acidosis, hyperammonaemia and fluid overload.
    • Do not routinely correct INR/platelets (INR is a prognostic marker and transplant criterion). FFP/factors only for active bleeding or procedures (e.g. ICP monitor). Hb transfusion target 70 g/L. Consider VTE prophylaxis daily.
    • Low threshold for empirical antibiotics if haemodynamics worsen or encephalopathy progresses.
    • Encephalopathy: move to ICU at first mental change; head up >30°, neutral head position; intubate at grade 3–4 (and before transfer if evolving).
    • Intracranial hypertension: highest risk with hyperacute/acute phenotype, young age, renal impairment, vasopressors and arterial ammonia >150–200 µmol/L that does not fall. Treat surges with mannitol or hypertonic saline ± short-term hyperventilation.
    • High-volume plasma exchange improves transplant-free survival (RCT); other liver support devices only in trials.
  • Cause-specific (2): autoimmune – early corticosteroids, but list for transplant if no improvement within 7 days; HELLP/AFLP – urgent delivery; HSV/VZV and HBV are screened for because they are treatable (2). Specific therapy (e.g. aciclovir for HSV, nucleos(t)ide analogue for HBV) per eTG.
  • Referral to a transplant unit – ANZ paracetamol guideline (3): any of INR >3.0 at 48 h or >4.5 at any time; oliguria or creatinine >200 µmol/L; pH <7.3 or arterial lactate >3 mmol/L; SBP <80 mmHg despite resuscitation; hypoglycaemia; severe thrombocytopenia; any encephalopathy or GCS <15 not explained by sedative co-ingestion.
  • Referral criteria – EASL (2):
    • Paracetamol/hyperacute: pH <7.30 or HCO3 <18; INR >3.0 on day 2 or >4.0 thereafter; oliguria/raised creatinine; altered consciousness; hypoglycaemia; lactate unresponsive to fluids.
    • Non-paracetamol: pH <7.30 or HCO3 <18; INR >1.8; oliguria/renal failure or Na <130; encephalopathy, hypoglycaemia or metabolic acidosis; bilirubin >300 µmol/L; shrinking liver.
  • King's College criteria for emergency transplant (2):
    • Paracetamol: arterial pH <7.3 after resuscitation and >24 h after ingestion; or lactate >3 mmol/L; or all three of grade 3–4 HE, creatinine >300 µmol/L and INR >6.5.
    • Non-paracetamol: INR >6.5; or 3 of 5 of: indeterminate/drug-induced aetiology, age <10 or >40 years, jaundice-to-encephalopathy >7 days, bilirubin >300 µmol/L, INR >3.5.
    • KCC: sensitivity about 69%, specificity about 92%; contraindications should not delay transfer (2).
  • Australian liver transplant units: Victorian Liver Transplant Unit (Austin Health, Melbourne; also covers abdominal organ retrieval for Tasmania) (6); Australian National Liver Transplant Unit (RPA, Sydney) (7); Queensland Liver Transplant Service (Princess Alexandra, Brisbane); plus units in Adelaide, Perth and Auckland (8).
  • 1-year survival after emergency transplant for ALF is about 80% (2).
Red flags and clinical pearls

Do not wait for deep coma or very high enzymes before referral; glucose and cerebral complications need monitoring.

  • Decompensated cirrhosis is different: see the Cirrhosis page and the GESA care bundle (1).
  • Falling aminotransferases with rising INR/bilirubin and a shrinking liver = worsening, not recovery (2).
  • Any encephalopathy with INR >1.5 = ALF: transfer early to a specialist unit (2).
  • Don't give FFP/vitamin K "to fix the INR" without talking to the transplant unit: it hides the most important prognostic marker (2)(3).
  • Hypoglycaemia, lactate >3 and pH <7.3 after resuscitation are among the strongest bad-prognosis signs in paracetamol ALF (2)(3).
  • Don't stop NAC at 20 h just because the bag finished: check ALT/INR/paracetamol first (3).
  • Check: pregnancy test in every woman of reproductive age (HELLP/AFLP need delivery, not just liver care) (2).
References
  1. GESA: Decompensated Cirrhosis Care Bundle
  2. EASL Clinical Practice Guidelines on acute (fulminant) liver failure, J Hepatol 2017;66:1047–81 – EASL slide summary
  3. Chiew AL et al. Updated guidelines for the management of paracetamol poisoning in Australia and New Zealand. MJA 2020;212(4):175–83
  4. Lee WM et al. IV N-acetylcysteine improves transplant-free survival in early stage non-acetaminophen ALF. Gastroenterology 2009;137:856–64
  5. AASLD/EASL 2014 practice guideline: Hepatic encephalopathy in chronic liver disease (West Haven grading)
  6. RACS / Austin Health: Victorian Liver Transplant Unit
  7. Sydney LHD: Liver transplant referrals (RPA)
  8. ANZ Liver and Intestinal Transplant Registry (ANZLITR) metadata

Last updated from Sen’s notes on 9 October 2026.