What is the management approach for acute liver failure?

Management of Acute Liver Failure

The management of acute liver failure requires immediate transfer to an intensive care unit in a liver transplant center, with comprehensive diagnostic workup, specific treatment based on etiology, and aggressive supportive care to prevent complications and improve survival outcomes. 1

Diagnostic Approach

• Critical etiologic investigations:

  • Serum acetaminophen levels (measure regardless of clinical history)
  • Viral hepatitis serologies
  • Toxicology screen
  • Hepatic Doppler ultrasound
  • Autoantibody testing for autoimmune hepatitis 1

• Laboratory workup:

  • Prothrombin time (PT)/INR, factor V
  • Complete blood count
  • Comprehensive metabolic panel
  • Liver function tests
  • Total bilirubin and albumin
  • Arterial blood gases with lactate
  • Ammonia levels 1

• Consider transjugular liver biopsy when etiology remains unclear after initial evaluation 1

Etiology-Specific Treatment

Acetaminophen-Induced ALF

• Administer N-acetylcysteine (NAC) immediately without waiting for acetaminophen levels 1, 2
• Dosing regimen: Loading dose of 150 mg/kg IV, followed by maintenance doses of 300 mg/kg divided into 3 sequential doses over 21 hours 1, 2
• Administer fresh frozen plasma (FFP) and vitamin K for severe coagulopathy 1
• Continue NAC if acetaminophen levels remain detectable or if ALT/AST are increasing or INR remains elevated after completion of standard regimen 2

Other Specific Causes

• Ischemic injury: Prioritize cardiovascular support 1
• Budd-Chiari syndrome: Consider expedited liver transplantation; rule out underlying malignancy 1
• Malignant infiltration: Diagnose via imaging and biopsy; treat underlying malignancy (transplantation not an option) 1
• Viral hepatitis: Specific antiviral therapy based on viral etiology
• Autoimmune hepatitis: Consider corticosteroids; non-responders may need urgent transplantation 1

General Supportive Management

Hemodynamic Support

• Assess volume status before initiating treatment
• Maintain euvolemia with crystalloid fluids
• Consider colloids (albumin preferred) for fluid resuscitation 1

Neurological Management

• Monitor for and treat hepatic encephalopathy
• Consider intracranial pressure monitoring in severe cases (Grade 3-4 encephalopathy)
• Elevate head of bed to 30 degrees
• Minimize stimulation and avoid sedatives when possible

Renal Support

• Use continuous modes (CVVH) rather than intermittent hemodialysis for acute renal failure requiring dialysis 1
• Monitor fluid balance and electrolytes carefully

Respiratory Support

• Consider mechanical ventilation for severe respiratory failure
• Note that ventilation >48 hours requires goals of care discussion 1

Infection Management

• Consider broad-spectrum empirical antibiotics in patients with worsening hepatic encephalopathy or signs of systemic inflammatory response syndrome 1
• Monitor for infections, particularly fungal pathogens
• Perform surveillance cultures regularly

Nutrition and Metabolic Support

• Initiate early enteral nutrition (approximately 60 grams of protein per day) 1
• Manage hypoglycemia with continuous glucose infusions
• Monitor and replace phosphate, magnesium, and potassium as needed 1

Transplantation Considerations

• Consider expedited liver transplantation for selected patients 1

• Specific indications for urgent transplantation:

  • Herpes virus hepatitis
  • Wilson disease
  • Fulminant autoimmune hepatitis unresponsive to steroids
  • Budd-Chiari syndrome 1

• Poor prognostic indicators:

  • ACLF with CLIF-C ACLF score ≥70 at 48 hours (100% 28-day mortality)
  • Four or more organ failures at Days 3-7 after diagnosis of ACLF-3 (90-100% mortality at 28-90 days) 1

Palliative Care Considerations

• Offer palliative care or hospice to patients expected to survive <6 months 1
• All patients with cirrhosis admitted to the ICU or with ACLF should receive a palliative care consult to:
  • Define prognosis
  • Determine goals of care
  • Document medical power of attorney and code status 1

Common Pitfalls and Caveats

• Delayed recognition: Early identification and transfer to a transplant center is critical for survival
• Inadequate monitoring: Patients can deteriorate rapidly; continuous monitoring of vital signs, mental status, and laboratory parameters is essential
• Missing acetaminophen toxicity: Always check acetaminophen levels regardless of history 1, 2
• Inadequate infection surveillance: Infections are common and can precipitate further deterioration
• Fluid management challenges: Patients require careful balance between adequate perfusion and avoiding fluid overload
• Delayed transplant evaluation: Early consultation with transplant team improves outcomes 3, 4