EBM Acute Liver Failure

Pedagogical disambiguation: Emergency Medicine Lecture Notes and Evidence Based emergency medicine principles from Professor A.F.T Brown and the Life in the Fast Lane team.


  • Hyperacute liver failure
    • Presents within 7 days of onset. 36% survival with medical management alone (single most common cause in UK and USA is paracetamol poisoning).
  • Acute liver failure
    • Encephalopathy, coagulopathy and jaundice presenting within 8-28 days in patient with previously normal liver. More likely (with hyperacute group) to get cerebral oedema (80%).
  • Subacute liver failure
    • Presents from 29-72 days, less likely to get cerebral oedema, but more likely to have ascites.  Poorer 14% survival.


  • Commonest causes (note wide geographic variation):
    • Viral: hepatitis A, E (faecal-oral), B +/- D, C, EBV, CMV, HSV, HZV, parvovirus B19. Hep G, TT, SEN very rarely implicated + unclear role.
    • Drugs: paracetamol poisoning (single most common cause ALF in USA) – deliberate or inadvertent from multiple doses (including children), volatile anaesthetics, idiosyncratic reactions to isoniasid / rifampicin / nitrofurantoin / NSAIDs / valproate / phenytoin / statin, Ecstasy (methylmetamphetamine).

Jalan R, Williams R, Bernuau J. Paracetamol: are therapeutic doses entirely safe? Lancet 2006; 368: 2195-6. [Reference]

  • Rare (5% causes):
    • Autoimmune CAH, Budd-Chiari, Wilson’s, fatty liver of pregnancy, pre-eclampsia (HELLP), mushrooms (Amanita spp), herbal remedies.
    • Malignancy, ischaemia, heat stroke, Reye’s.


  • General supportive:
    • Hospitalise if INR >1.5; IPPV for Grade 3 or 4 coma or respiratory failure, invasive monitoring including ICP monitor (ICP < 25 mmHg) +/- jugular bulb O2 (NB: clinical signs / imaging unreliable to detect the earliest signs cerebral oedema), infusion 5-10% dextrose (watch for hyponatraemia), fluids and vasopressor noradrenaline therapy. GI bleeding prophylaxis.
  • Specific to complications:
    • Encephalopathy with cerebral oedema. Correct avoidable factors (hypoxia, sepsis, hyperthermia, haemorrhage, hypokalaemia, benzodiazepines), monitor ICP early. Give mannitol 0.5 g/kg if ICP ≥ 25 mmHg, or hypertonic saline 7.5% boluses 2.0 mL/kg. Moderate hypothermia 32-33OC (e.g. awaiting transplantation) being trialed.
    • Lactulose and neomycin appear not to work, and have complications such as aspiration and nephrotoxicity, respectively.
    • Infection. Daily surveillance for bacterial (S.aureus, S.pneumoniae and E.coli) and fungal (Candida) infections, including primary peritonitis.  Empiric and or prophylactic broad-spectrum antibiotics + antifungals given.
    • Microcirculatory / haemodynamic failure including acute oliguric renal failure. Epoprostenol (PGI2), angiotensin, vasopressors, NOS antagonists.
    • Coagulopathy. Vit K 10 mg IV; FFP / platelets for active bleeding; recombinant Factor VIIa (rFVIIa) with FFP – use declining + many C/Is.
    • N. acetylcysteine IV for paracetamol poisoning ideally within 24 hours, but even if ingested 48-72 hours before (given within 8-10 hours risk is nil to minimal).
    • Orthotopic liver transplantation (OLT). Note there are different referral criteria for paracetamol poisoning from all other causes such as INR >3.0 / hypoglycaemia/ acidosis pH <7.30 / encephalopathy on Day 2.
      • liver unit referral shows 60->80% one year survival in selected patients. If in doubt – ring and discuss early
    • Liver support systems. ‘Bridging support’ to transplantation, but no conclusive evidence of benefit. Hepatocyte infusion experimental.

Shawcross D, Jalan R. Dispelling myths in the treatment of hepatic encephalopathy. Lancet 2005; 365:431-3. [Reference]

Bernal W, Auzinger G, Dhawan et al. Acute liver failure. Lancet 2010;376:190-201. [Reference]

Stravitz R, Kramer A, Davern T et al. Intensive care of patients with acute liver failure: Recommendations of the US Acute Liver Failure Study Group. Crit Care Med 2007;35:2498-2508. [Reference]

Acute on Chronic Liver Failure

  • Acute deterioration in liver function over days to weeks in patients with pre-existing chronic liver disease (CLD). Poor prognosis from underlying cirrhosis and end-stage liver disease (ESLD) with portal hypertension, ascites and multi-organ failure.
  • Much more common than ALF. Features include jaundice, coagulopathy, encephalopathy (precipitated by sepsis including spontaneous bacterial peritonitis, or GI bleed, alcohol, constipation, hypokalaemia, and drugs including NSAIDs and sedatives), hepatorenal syndrome and hepatopulmonary syndrome.

Macnaughtan J, Thomas H. Liver failure at the front door. Clinical Medicine 2010;10:73-8. [Reference]

Bailey C, Hern H. Hepatic failure: An evidence-based approach in the emergency department. Emergency Medicine Practice 2010;12(4):1-24. [Reference]

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