What is the management of Acute Liver Failure (ALF)?

Management of Acute Liver Failure

Immediate Actions and ICU Admission

All patients with acute liver failure must be admitted to an intensive care unit immediately, and early contact with a liver transplant center should be initiated without delay. 1

• Transfer to a transplant center early in the evaluation process, as the "transplantation window" is often narrow and post-transplant survival rates reach 80-90%. 1
• Admit any patient with prolonged prothrombin time (INR ≥1.5) and any evidence of altered mental status to the ICU, as the condition may deteriorate rapidly. 2, 1
• Continuous monitoring of liver, kidney, brain, lung, coagulation, and circulation is required in all ALF patients. 1

Etiology-Specific Management

Acetaminophen Toxicity

Administer N-acetylcysteine immediately for all suspected acetaminophen-induced ALF, even if >48 hours since ingestion. 1, 3

• Loading dose: 140 mg/kg orally or via nasogastric tube, followed by 70 mg/kg every 4 hours for 17 doses. 1, 3
• If presentation is within 4 hours of ingestion, give activated charcoal (1 g/kg orally) just prior to NAC. 1
• Continue NAC for the full 21-hour course (3-bag IV method: 300 mg/kg total dose) even if acetaminophen levels become undetectable. 3
• For massive overdose or if ALT/AST continue rising after completion, continue NAC beyond 21 hours and contact poison control. 3

Autoimmune Hepatitis

• Obtain liver biopsy via transjugular approach to confirm diagnosis. 2, 1
• Treat with prednisone 40-60 mg/day immediately. 1
• List for transplantation even while administering corticosteroids, as response may be inadequate. 1

Viral Hepatitis

• Hepatitis A and B require supportive care only; no virus-specific treatment has proven effective. 1
• For herpes simplex virus or varicella zoster, immediately list for transplant and treat with acyclovir. 1
• For hepatitis B patients requiring chemotherapy/immunosuppression, give nucleoside analogs prophylactically. 1

Wilson Disease

• Wilson disease-related ALF is uniformly fatal without transplantation. 1
• Treat acutely with albumin dialysis, continuous hemofiltration, plasmapheresis, or plasma exchange to lower serum copper and limit hemolysis. 1
• Do NOT use penicillamine due to hypersensitivity risk. 1

Acute Fatty Liver of Pregnancy/HELLP Syndrome

• Consult obstetrics immediately and perform expeditious delivery. 1
• Recovery is typically rapid after delivery with supportive care only. 1

Drug-Induced Hepatotoxicity

• Discontinue all non-essential medications immediately. 1
• Obtain detailed medication history including prescription drugs, over-the-counter medications, herbs, and dietary supplements. 1

Mushroom Poisoning

• Consider penicillin G and silymarin administration. 1
• List for transplantation immediately, as this is often the only lifesaving option. 1

Hemodynamic Management

Maintain mean arterial pressure ≥50-60 mm Hg through aggressive fluid resuscitation first, followed by vasopressors if needed. 2, 1

• Fluid resuscitation with colloid (albumin) is preferred over crystalloid (saline); all solutions should contain dextrose to maintain euglycemia. 2
• Consider pulmonary artery catheterization in hemodynamically unstable patients to assess volume status. 2, 1
• If fluid replacement fails, use epinephrine, norepinephrine, or dopamine—NOT vasopressin. 2, 1
• Dopamine has been associated with increased systemic oxygen delivery in ALF. 2

Neurological Management

Hepatic Encephalopathy Monitoring

• Monitor mental status frequently and transfer to ICU if level of consciousness declines. 1
• Position patient with head elevated at 30 degrees and minimize stimulation. 1
• For grades III-IV encephalopathy, intubate for airway protection. 1

Sedation

• Use propofol for sedation due to favorable pharmacokinetics. 2, 1
• Avoid benzodiazepines as they worsen encephalopathy; flumazenil may lower encephalopathy scores if benzodiazepines were given. 2
• Avoid dexmedetomidine due to exclusive hepatic metabolism. 2

Seizure Control

• Control seizures with phenytoin; add diazepam only as needed. 1

Intracranial Pressure Management

• Consider lactulose to reduce ammonia levels, though evidence for improved outcomes is limited. 1
• Maintain serum sodium at 140-145 mmol/L; infusion of hypertonic saline significantly decreases ICP. 2
• Avoid sodium corrections exceeding 10 mmol/L per 24 hours. 2
• ICP monitoring devices have been associated with hemorrhagic complications (7-20% of cases) and have not demonstrated mortality benefit. 2
• Transcranial Doppler ultrasound is a useful first-line monitoring tool. 2

Coagulation Management

Reserve fresh frozen plasma and coagulation factors for active bleeding or invasive procedures only. 2, 1

• Administer vitamin K to all patients with ALF. 1
• Give platelets for counts <10,000/mm³ or before invasive procedures. 1
• Consider recombinant activated factor VII for invasive procedures. 1
• Prophylactic administration of coagulation factors precludes assessment of disease progression and is not supported. 2
• Most ALF patients have rebalanced hemostasis between pro- and anticoagulant factors; bleeding complications occur in only 10% of patients. 2

Renal Management

If dialysis is needed, use continuous renal replacement therapy rather than intermittent hemodialysis. 2, 1

• Avoid nephrotoxic agents including NSAIDs. 1
• Regional citrate anticoagulation should be monitored due to potential metabolic effects in ALF. 2
• Early commencement of CRRT to control hyperammonemia is now considered standard of care. 4

Metabolic Management

• Monitor blood glucose at least every 2 hours and manage hypoglycemia with continuous glucose infusions. 2, 1
• Monitor and supplement phosphate, magnesium, and potassium levels frequently throughout the hospital course. 2, 1
• Target serum sodium at 140-145 mmol/L. 2, 1
• Check coagulation parameters, complete blood counts, metabolic panels, and arterial blood gases frequently. 2, 1

Nutritional Support

• Initiate enteral feedings early with moderate protein intake (approximately 60 grams per day). 2, 1
• Severe protein restrictions should be avoided. 2
• Branched-chain amino acids have not been shown superior to other enteral preparations. 2
• If enteral feedings are contraindicated (e.g., severe pancreatitis), use parenteral nutrition despite increased fungal infection risk. 2, 1

Infection Prevention and Management

• Screen aggressively for infections and treat early, as bacterial infections are common precipitants. 1
• Prophylaxis for stress ulceration with H2 blockers or proton pump inhibitors is recommended. 1
• Enteral and parenteral nutrition may reduce gastrointestinal bleeding risk from stress ulceration. 2

Liver Transplantation

Urgent hepatic transplantation is indicated when prognostic indicators suggest high likelihood of death. 2, 1

• King's College criteria remain the best prognostic tool, though sensitivity is limited (50-60%). 1
• Poor prognostic indicators include idiosyncratic drug injury, non-hepatitis A viral infections, autoimmune hepatitis, mushroom poisoning, Wilson disease, Budd-Chiari syndrome, and indeterminate cause. 1
• Post-transplant survival rates reach 80-90% even in patients with multiple organ failures. 1, 5
• In the largest U.S. study, only 29% of patients received a liver graft, while 10% died on the waiting list. 2

Liver Support Systems

• Plasma exchange may stabilize patients and serve as bridging therapy until transplantation, particularly in Wilson disease. 1
• Various liver support systems (MARS, bioartificial liver) have been tested, but well-designed RCTs have failed to demonstrate significant mortality reduction. 2
• These techniques should not delay transfer to a transplant center. 2

Common Pitfalls

• Do not use systemic corticosteroids for general ALF treatment (except autoimmune hepatitis). 2
• Changes in aminotransferase levels correlate poorly with prognosis. 2
• Consider malignant infiltration in patients with previous cancer history or massive hepatomegaly; obtain imaging and biopsy. 2
• If etiology remains unclear after extensive evaluation, transjugular liver biopsy may identify specific diagnoses. 2, 1