Acute Liver Failure

Background

• Uncommon (~400/year; 70% due to paracetamol overdose) but serious deterioration of liver function.  Can be very difficult to manage (many cases will require super-urgent transplant)
• It can be useful to classify liver failure as
  • Hyperacute (0-7 days- most commonly paracetamol OD- 30% transplant free survival)
  • Acute (7-28 days- usually viral origin- 33% transplant free survival)
  • Subacute (>28 days- usually non-paracetamol drug related- 14% TFS)
    • NB This can be difficult to differentiate from acute on chronic liver disease so a detailed history and careful investigation is key

Aetiology/Pathophysiology

• Any cause of liver damage can produce acute liver failure
  • Most commonly drugs e.g. paracetamol (40%); other drugs (13%)
  • Hepatitis A (4%), B (7%), E
  • Other causes include toxins, Wilson’s disease (3%), Autoimmune hepatitis (4%), Liver mets, Shock/Cardiac failure, Budd-Chiari syndrome (3%); Acute fatty liver of pregnancy (1%); HELLP syndrome (1%)
  • 10-15% have unknown cause (cryptogenic)

Presentation/Assessment

• Cerebral disturbance (hepatic encephalopathy and/or cerebral oedema) is the main feature, although early on this may be mild/episodic
  • Reduced alertness/poor concentration may be earliest signs; restlessness/irritability followed by reduced consciousness, stupor and coma
    • Cerebral oedema may also cause abnormally reacting/fixed pupils, hypertension, bradycardia, hyperventilation, sweating, myoclonus, fits/decerebrate posturing
    • Weakness, nausea and vomiting are common
    • right hypochondrial pain may be present but signs of chronic liver disease e.g. ascites, hepatosplenomegaly, jaundice (although more likely) are rarely present unless there is acute on chronic disease
  • Grading Encephalopathy
    1. Altered mood, impaired concentration and psychomotor function, rousable
    2. Drowsy, inappropriate behaviour, able to talk
    3. Very drowsy, disorientated, agitated, aggressive
    4. Coma, may respond to painful stimuli

Diagnosis/Investigation

• Diagnosis can be defined as
  • absence of chronic liver disease
  • acute hepatitis (raised ALT/AST) accompanied by coagulopathy (INR >1.5)
  • any degree of mental alteration (encephalopathy)
  • Illness <26 weeks
• Investigations include
  • Blood tests
    • FBC and Clotting/Coagulation (raised INR/PTt)
    • LFTs (acutely raised ALT/AST; raised bilirubin (>300μmol/l indicates severe disease); albumin often normal (chronic marker)
    • U&Es (hepatorenal failure- often AKI will also be present; hyponatraemia and metabolic acidosis are often present)
    • Glucose (hypoglycaemia)
    • ABGs (metabolic acidosis)
    • Others should be done to try and identify a cause e.g.
      • Paracetamol/Salicylate levels
      • Ceruloplasmin, Alpha-1-antitrypsin, serum copper
      • Amylase/lipase
      • Antinuclear antibody, Anti smooth muscle antibody
      • Serum ferritin, iron, transferrin
      • Pregnancy test
      • HIV antibody
      • Viral Hepatitis serology and other viral serology e.g. HSV, EBV, CMV
  • Hepatic Doppler USS (often helps exclude chronic disease; Budd-Chiari syndrome and malignancy)
  • Liver biopsy is rarely performed in the acute setting as coagulopathy increases the risk of severe bleeding.  (May be performed later if required)
• Adverse prognostic features (Kings College Hospital Criteria for superurgent liver transplant listing)
  • Paracetamol poisoning
    • pH<7.3 at or beyond 24 hours after OD OR
    • Serum creatinine >300μmol/l (~3.38mg/dl) plus prothrombin time >100s plus encephalopathy grade 3/4
  • Non-paracetamol
    • Prothrombin time >100s OR
    • Any three of
      • Jaundice to encephalopathy time >2 days
      • Age <10 or >40
      • Indeterminate or drug causes
      • Bilirubin >300μmol/l
      • Prothrombin time >50s
    • Factor V level <15% and encephalopathy grade 3/4
  • NB Encephalopathy grade 3/4 is generally an indication for intubation and management in ICU/HDU- close monitoring of cardiovascular, renal, neurological, hepatic function etc

Management

• management of paracetamol poisoning; treat the underlying cause where possible
• Neurology
  • Protective measures e.g. elevate head to 30°; sedation; avoid hypotension; prevent hypoxaemia (oxygen); ventilate to target CO2 of 4.7kPa-5.2kPa; tight glycaemic control
  • Treat intracranial hypertension with hypertonic saline or manitol
• Fluid resuscitation and close fluid monitoring (catheterisation)
• Plasma transfusion if coagulopathy is severe
• Liver transplant can be an option for those who meet the Kings College criteria (above)

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