What is the initial treatment for acute liver failure?

Initial Treatment for Acute Liver Failure

The initial treatment for acute liver failure (ALF) requires immediate hospital admission, preferably to an intensive care unit (ICU), with careful monitoring of mental status, prothrombin time, and implementation of supportive care measures tailored to the underlying etiology. 1, 2

Diagnosis and Initial Assessment

• ALF is defined by the presence of coagulopathy (prothrombin time prolonged by ≥4-6 seconds or INR ≥1.5) and any degree of altered mental status in a patient without pre-existing liver disease, with illness duration ≤26 weeks 1
• Immediate laboratory evaluation should include prothrombin time/INR, comprehensive metabolic panel, arterial blood gases, lactate, complete blood count, acetaminophen level, toxicology screen, viral hepatitis serologies, and other tests based on clinical suspicion 1
• Transjugular liver biopsy may be considered in cases of indeterminate etiology to guide specific treatment approaches 2

Etiology-Specific Initial Treatments

• For acetaminophen-induced ALF, N-acetylcysteine (NAC) should be administered immediately (140 mg/kg orally or via nasogastric tube followed by 70 mg/kg every 4 hours for 17 doses) even if >48 hours since ingestion 1
• For viral hepatitis A and B, supportive care is the mainstay as no virus-specific treatments have proven effective 2
• Patients with suspected herpes virus or varicella zoster as the cause must be treated immediately with acyclovir and placed on the liver transplant list 2
• For autoimmune hepatitis, corticosteroids (prednisone 40-60 mg/day) should be initiated while simultaneously listing for transplantation 2
• In mushroom poisoning, consider administration of penicillin G and silymarin while listing for transplantation 2
• For Wilson disease, initiate treatment to lower serum copper through albumin dialysis, continuous hemofiltration, plasmapheresis, or plasma exchange (avoid penicillamine due to hypersensitivity risk) 2
• In acute fatty liver of pregnancy/HELLP syndrome, expedite delivery in consultation with obstetrical services 2
• For drug-induced hepatotoxicity, discontinue all but essential medications 2

Supportive Care Management

Hemodynamic Support

• Carefully assess fluid status and provide resuscitation to maintain adequate intravascular volume 2
• If fluid replacement fails to maintain mean arterial pressure of 50-60 mmHg, initiate vasopressor support with agents such as norepinephrine, epinephrine, or dopamine (avoid vasopressin) 2
• Consider pulmonary artery catheterization in hemodynamically unstable patients 2

Metabolic Management

• Manage hypoglycemia with continuous glucose infusions, targeting an upper blood glucose level ≤180 mg/dL 2, 3
• Monitor and supplement phosphate, magnesium, and potassium levels as needed 2
• Initiate early enteral nutrition with moderate protein intake (approximately 60 grams per day) 2
• If enteral feeding is contraindicated, consider parenteral nutrition despite increased risk of fungal infection 2

Central Nervous System Management

• Position patient with head elevated at 30 degrees and minimize stimulation 2
• For grades III-IV encephalopathy, perform endotracheal intubation for airway protection 2
• Control seizures with phenytoin, avoiding benzodiazepines when possible 2
• Consider lactulose administration to reduce ammonia levels, though evidence for improved outcomes is limited 2

Coagulation Management

• Administer vitamin K to all patients with ALF 2
• Reserve fresh frozen plasma for active bleeding or invasive procedures 2
• Provide platelets for counts <10,000/mm³ or before invasive procedures 2
• Consider recombinant activated factor VII for invasive procedures 2

Infection Prevention and Management

• Administer empiric broad-spectrum antibiotics within 1 hour if sepsis is suspected 3
• Obtain blood cultures before starting antibiotics, but do not delay antibiotic administration 3
• Consider third-generation cephalosporins, piperacillin-tazobactam, or fluoroquinolones for empiric coverage 3
• Implement prophylaxis for stress ulceration with H2 blockers or proton pump inhibitors 2

Renal Support

• Avoid nephrotoxic agents 2
• If dialysis is needed for acute renal failure, use continuous modes rather than intermittent hemodialysis 2, 3
• Consider early continuous renal replacement therapy to control hyperammonemia 4

Liver Transplantation Considerations

• Urgent hepatic transplantation evaluation should be initiated when prognostic indicators suggest a high likelihood of death 2
• Poor prognostic indicators include idiosyncratic drug injury, non-hepatitis A viral infections, autoimmune hepatitis, mushroom poisoning, Wilson disease, Budd-Chiari syndrome, and indeterminate cause 2
• Post-transplant survival rates for ALF have been reported as high as 80-90% 2

Common Pitfalls and Caveats

• Diagnosing sepsis in ALF is challenging due to impaired lactate clearance, baseline vasodilation, and often absent fever 3
• Changes in aminotransferase levels correlate poorly with prognosis in ALF patients 2
• Malignant infiltration of the liver can mimic ALF and should be considered in patients with previous cancer history or massive hepatomegaly 2
• Liver support systems (including sorbent systems and bioartificial liver) have shown limited evidence of efficacy and are not currently recommended as standard treatment 2