Acute Liver Failure: Lecture Notes

Definition

• 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.

Aetiology

• Commonest causes:
  • Viral hepatitis A, B, C, D, E, F, G, EBV, CMV, HSV, HZV.
  • Drugs including paracetamol poisoning – including multiple doses, often inadvertently in children, volatile anaesthetics, idiosyncratic reactions to rifampicin / isoniasid / NSAIDs / valproate and use of Ecstasy (methylmetamphetamine).

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

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

Management

• General supportive:
  • Hospitalize 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, hemorrhage, 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. Lactulose and neomycin appear not to work, and have complications such as aspiration and nephrotoxicity, respectively.

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

• 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 contraindications.
• N. acetylcysteine IV for paracetamol poisoning, even if ingested 48-72 hours before.
• Orthotopic liver transplantation (OLT). Note there are different referral criteria for paracetamol poisoning from all other causes eg INR >3.0 / hypoglycaemia/ acidosis pH <7.30 / encephalopathy on Day 2.- liver unit referral may show 60->80% one year survival in selected patients. If in doubt – ring and discuss early…
• Liver support systems. ‘Bridging support’ to transplantation, but no convincing outcome efficacy data yet

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]

O’Grady JG. Acute liver failure. Postgrad Med J 2005; 81:148-54. [Reference]

Lai W, Murphy N. Management of acute liver failure. Cont Educ Anaes, Crit Care & Pain 2004; 4: 40-43. [Reference]

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