Management of Acute Liver Failure

Definition of Acute Liver Failure (ALF): ALF refers to a highly specific and rare syndrome, characterised by an acute abnormality in liver function tests in an individual without underlying chronic liver disease. The disease process is associated with development of a coagulopathy of liver aetiology, and clinically apparent altered level of consciousness due to hepatic encephalopathy occurring within days to a few weeks of the appearance of the first symptoms (usually jaundice) and in the absence of pre-existing liver disease.  

Introduction

  • Most acute admissions for liver failure occur in patients with pre-existing liver disease.
  • Acute liver failure strictly refers to those patients without such a history, and is much rarer.

Aetiology

The causes of acute liver failure in the UK are, in order of incidence:

  • Paracetamol overdose (70%)
  • Viral Hepatitis, including A, B, C and E (8.4%)
  • Idiosyncratic drug reaction, including tricyclic antidepressants, MAOIs, isoniazid, NSAIDs (5.1%)
  • Budd-Chiari (2.1%)
  • Autoimmune (2%)
  • Ischaemic (2%)
  • Miscellaneous, including fatty liver, hyperthermia, pregnancy, veno-occlusive disease and Wilson’s disease (10.4%)

(Reference: Edinburgh Royal Infirmary 2009)

Clinical features

  • Encephalopathy
  • Jaundice: may be minimal in early stages
  • Metabolic acidosis and renal failure may be early and marked in paracetamol overdose
  • Coagulopathy and hypoalbuminemia: Prolonged INR +/- low albumin in a patient with an acute severe liver injury (usually significantly elevated ALT present) but with no evidence of previous liver disease or cirrhosis is at high risk of developing ALF and should be considered for urgent discussion with the liver transplantation unit.
  • Hypoglycaemia

N.B. High risk of mortality within 24 hours if encephalopathy (+/- hypoglycaemia) is present, unless the following action is taken:

    • ITU review to consider immediate intubation to protect the airway if grade III or IV encephalopathy
    • Discussion with the liver transplant registrar as soon as possible.

Assessment / monitoring

  • Immediate: LFTs, FBC, coagulation screen, blood glucose, U&Es, paracetamol levels, blood and urine cultures.
  • Urgent (within 24 hours): full liver screen, hepatitis serology (IgM anti-HAV, HBsAg, IgM anti-HBc and anti-HCV, HEV), CMV and EBV.
  • 12hourly bloods thereafter (regardless of aetiology): LFTs, FBC, U&Es, coagulation screen, arterial blood gases (including lactate), bone profile, magnesium.
  • Chest x-ray, ultrasound (US) of liver and pancreas.
  • Pregnancy test (if appropriate).

Consider:

  • Serum caeruloplasmin, serum copper.
  • Doppler US of hepatic vein if Budd-Chiari suspected.
  • EEG if doubt about the aetiology of cerebral dysfunction.

General management and treatment options

Seek senior help early as ITU admission may be required. Your consultant should be aware of the patient on the day of admission so that early discussions can take place with relatives and the Liver Transplant Unit if needed.

General

  • Consider the administration of N-acetylcysteine (off-label use) in all patients with acute liver failure, regardless of aetiology. Discuss with gastroenterologist.
  • Monitor urine output hourly (consider catheterisation), blood glucose every 2 hours.
  • Avoid all sedating agents (unless the patient is intubated), NSAIDs and intramuscular administration of any agents.
  • Avoid arterial puncture (except in paracetamol overdose where a lactate level provides important prognostic information).

Encephalopathy

  • If cerebral oedema suspected, consider imaging. 
  • If Grade II or worse on presentation, and cerebral oedema is suspected, nurse the head in a 20 - 300 elevated position and give mannitol IV 20%, 0.5g/kg over 30 - 60 minutes and repeat 4 hourly if necessary, if cerebral oedema confirmed.
  • Grade III or IV encephalopathy is an indication for ITU transfer and elective intubation.

Hypoglycaemia

  • Glucose IV 10% at a rate of 100ml/hour. For moderate/severe hypoglycaemia see guideline on Management of Hypoglycaemia. Monitor glucose levels twice daily.
  • Continuous infusion of glucose may cause hyponatraemia which may predispose to cerebral oedema. Therefore the recommendation is to give concurrent:
    • sodium chloride IV 0.9% plus
    • potassium chloride IV 40mmol/L if hypokalaemic. Do not exceed maximum infusion rate (10mmol/hour).

Coagulopathy

  • Do not give blood products (i.e. fresh frozen plasma, factor concentrates) unless bleeding is a problem.
  • Vitamin K1 (phytomenadione) does not correct clotting defect but give phytomenadione 10mg slow IV bolus over 3 - 5 minutes to ensure patient is replete. Give further doses on day 2 and day 3.

If bleeding occurs

  • Discuss with Haematologist

Sepsis

  • Culture blood and urine at baseline and every 24 hours.

Renal failure

  • If K+ >6mmol/L, HCO3- <15mmol/L or creatinine >400micromol/L, the patient will need renal support. Discuss with the renal unit regarding modality.

Indication for discussion with the Scottish Liver Transplant Unit (SLTU) in Acute Liver Failure

Rather than waiting until the strict criteria for transplantation are met, patients with severe acute liver failure should be discussed with the Scottish Liver Transplant Unit (see Appendix 6 for contact details) at an early stage. This should occur if:

  • Prothrombin time >20 seconds or INR >2
  • pH <7.3 or H+ >50nmol/L
  • Hypoglycaemia
  • Conscious level impaired
  • Creatinine >200micromol/L
  • Any patient with encephalopathy, coagulopathy or renal impairment complicating acute liver injury should be discussed with SLTU.

 

Guideline reviewed June 2022
Page updated May 2023



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