Treatment of Acute Liver Failure
Early referral to a liver transplant center is essential for all patients with acute liver failure, as liver transplantation is often the only life-saving option for many etiologies including mushroom poisoning, herpes virus hepatitis, Wilson disease, and fulminant autoimmune hepatitis unresponsive to steroids. 1
Etiology-Specific Treatment
Acetaminophen Overdose
- Administer N-acetylcysteine (NAC) immediately 2
- Loading dose followed by maintenance doses over 21 hours
- Use Rumack-Matthew nomogram to guide treatment decisions
- NAC is most effective when given within 8 hours of ingestion but should not be withheld even if presentation is delayed
Viral Hepatitis
- Hepatitis A and B: Primarily supportive care 3, 1
- Hepatitis B reactivation: Nucleoside analogs should be given prior to and continued for 6 months after completion of chemotherapy in HBsAg-positive patients 3
- Herpes virus infection: Immediate acyclovir treatment and listing for transplantation 3, 1
Mushroom Poisoning
Wilson Disease
- Uniformly fatal without transplantation 3
- While awaiting transplantation, consider plasmapheresis, hemofiltration, exchange transfusion, or albumin dialysis 1
Drug-Induced Hepatotoxicity
- Discontinue all but essential medications 3
- Obtain detailed medication history including prescription, non-prescription drugs, herbs, and dietary supplements 3
Pregnancy-Related Liver Conditions
- For acute fatty liver of pregnancy or HELLP syndrome: Obstetrical consultation and expeditious delivery 1
Supportive Care Measures
Cardiovascular Support
- Primary treatment is cardiovascular support 1
- Address underlying causes of hypotension/hypoperfusion
Coagulation Management
- Administer vitamin K 1
- Give fresh frozen plasma only for active bleeding or invasive procedures 1
- Administer platelets for counts <10,000/mm³ or before invasive procedures 1
Infection Prevention and Management
- Monitor for bacterial infections (60-80% of ALF patients) and fungal infections (one-third of ALF patients) 1
- Administer empirical broad-spectrum antibiotics if signs of sepsis or worsening encephalopathy are present 1
- Provide stress ulcer prophylaxis with H2 blockers or PPIs 1
Metabolic Support
- Monitor glucose every 2 hours and treat hypoglycemia with continuous glucose infusions 1
- Target sodium levels between 140-145 mmol/L 1
- Monitor and replace phosphate, magnesium, and potassium as needed 1
Neurological Support
- Avoid sedation in patients without intracranial hypertension 1
- Minimize patient stimulation and avoid procedures that cause straining 1
- Monitor for cerebral edema, a leading cause of death in ALF 4
Renal Support
- Use continuous modes of hemodialysis rather than intermittent hemodialysis for acute renal failure 1
- Avoid nephrotoxic agents 1
Nutrition Support
- Initiate early enteral nutrition with approximately 60 grams of protein per day 1
Liver Support Systems
- Extracorporeal liver support systems (MARS, Prometheus) have not demonstrated significant survival benefits in randomized controlled trials 1
- These techniques should not delay transfer to a liver transplantation center 1
- Therapeutic plasma exchange may be useful, especially in non-transplant centers 4
Prognostic Considerations and Transplantation
- Early identification of patients who will require transplantation is critical 1, 4
- Poor prognostic indicators include:
Important Caveats
- The reported history of acetaminophen ingestion is often inaccurate and not a reliable guide to therapy 2
- The nomogram may underestimate hepatotoxicity risk in patients with chronic alcoholism, malnutrition, or those taking CYP2E1 enzyme-inducing drugs 2
- Delaying referral to a liver transplantation center significantly worsens outcomes 1
- Sepsis with multiorgan failure and cerebral edema remain the leading causes of death in ALF 4