What is the management approach for acute liver failure?

Management of Acute Liver Failure

Immediate Actions and ICU Admission

All patients with acute liver failure (defined as coagulopathy with INR ≥1.5 and any degree of altered mental status in patients without pre-existing liver disease) must be admitted to an intensive care unit with frequent monitoring, and early contact with a liver transplant center should be initiated immediately. 1, 2

• Transfer to ICU is mandatory when prothrombin time is prolonged by 4-6 seconds or more (INR ≥1.5) with any evidence of altered sensorium 3
• Continuous monitoring of liver, kidney, brain, lung, coagulation, and circulation is required 3
• Contact a transplant center early in the evaluation process, as the "transplantation window" is often narrow 1, 2

Etiology Determination and Specific Antidotes

Universal N-Acetylcysteine Administration

Start N-acetylcysteine immediately in ALL patients with acute liver failure, regardless of etiology, as it improves transplant-free survival even in non-acetaminophen cases. 2

• Loading dose: 150 mg/kg IV over 15 minutes, followed by 50 mg/kg over 4 hours, then 100 mg/kg over 16 hours 1, 4
• Alternative oral dosing: 140 mg/kg by mouth or nasogastric tube, followed by 70 mg/kg every 4 hours for 17 doses 1
• NAC reduces progression to grade III-IV encephalopathy and mortality 2
• Continue NAC even if >48 hours since acetaminophen ingestion 1, 3

Essential Diagnostic Workup

Obtain immediately 1, 3:

• Acetaminophen level (even without history of ingestion—very high aminotransferases >3,500 IU/L suggest acetaminophen toxicity) 1
• Prothrombin time/INR, comprehensive metabolic panel, arterial blood gases, lactate 3
• Complete blood count, toxicology screen, viral hepatitis serologies (HAV IgM, HBsAg, anti-HBc IgM, HCV RNA, HEV in endemic areas) 1, 3
• Ceruloplasmin, 24-hour urine copper, and slit-lamp examination if age <40 years (Wilson disease) 1
• Autoimmune markers (ANA, ASMA, IgG) if suspected 1

Etiology-Specific Treatments

Acetaminophen toxicity:

• Activated charcoal (1 g/kg orally) if presentation within 4 hours of ingestion, given just prior to NAC 1
• NAC as described above 1, 4

Herpes simplex virus or varicella zoster:

• Immediate acyclovir and urgent transplant listing 3
• Consider in immunosuppressed patients or third-trimester pregnancy 5

Autoimmune hepatitis:

• Liver biopsy to confirm diagnosis 1, 3
• Prednisone 40-60 mg/day 1, 3
• List for transplantation even while administering corticosteroids 1, 3

Amanita phalloides mushroom poisoning:

• Penicillin G (300,000 to 1 million units/kg/day IV) and silymarin (30-40 mg/kg/day for 3-4 days) 5, 3
• List for transplantation immediately—often the only lifesaving option 5, 3

Wilson disease:

• Uniformly fatal without transplantation 3
• Albumin dialysis, continuous hemofiltration, plasmapheresis, or plasma exchange to lower serum copper and limit hemolysis 3
• Do NOT use penicillamine (risk of hypersensitivity) 3

Acute fatty liver of pregnancy/HELLP syndrome:

• Expeditious delivery with obstetrical consultation 1, 5, 3
• Recovery typically rapid after delivery with supportive care only 1, 3

Ischemic hepatitis ("shock liver"):

• Cardiovascular support is the treatment of choice 1
• Transplantation seldom indicated 1

Budd-Chiari syndrome:

• Transplantation indicated if significant liver failure present 1
• Exclude underlying malignancy before transplantation 1

Drug-induced hepatotoxicity:

• Discontinue all non-essential medications 3
• Obtain detailed medication history including prescription drugs, over-the-counter medications, herbs, and dietary supplements 3

Hemodynamic Management

Use albumin as first-line fluid resuscitation rather than crystalloid, with all solutions containing dextrose to maintain euglycemia. 2

• Maintain mean arterial pressure ≥50-60 mmHg through aggressive fluid resuscitation first 1, 2, 3
• Consider pulmonary artery catheterization in hemodynamically unstable patients 3
• If fluid replacement fails, initiate vasopressors: epinephrine, norepinephrine, or dopamine (NOT vasopressin) 1, 2, 3

Metabolic Management

Monitor blood glucose at least every 2 hours and maintain normoglycemia with continuous glucose infusions, as hypoglycemia can mimic hepatic encephalopathy. 2, 3

• Target serum sodium 140-145 mmol/L; correct sodium abnormalities no faster than 10 mmol/L per 24 hours 2
• Monitor and supplement phosphate, magnesium, and potassium levels as needed 3
• Initiate enteral feedings early with moderate protein intake (approximately 60 grams per day) 3
• If enteral feeding contraindicated, use parenteral nutrition despite increased fungal infection risk 3

Encephalopathy and Neurological Management

Position patient with head elevated at 30 degrees and minimize stimulation. 3

• Intubate for airway protection when Glasgow Coma Scale <8 or grade III-IV encephalopathy 2, 3
• Use propofol for sedation (favorable pharmacokinetics); avoid benzodiazepines as they worsen encephalopathy 3
• Avoid dexmedetomidine due to exclusive hepatic metabolism 3
• Control seizures with phenytoin; add diazepam only as needed 3
• Consider lactulose to reduce ammonia levels, though evidence for improved outcomes is limited 3

Mechanical Ventilation

Use protective mechanical ventilation settings per critical care guidelines, avoiding high PEEP levels (>10 cmH₂O) due to risk of hepatic congestion. 2, 3

Coagulation Management

Do NOT routinely correct coagulation abnormalities; restrict clotting factor administration to active bleeding or high-risk invasive procedures only. 2

• Administer vitamin K to all patients 3
• Reserve fresh frozen plasma for invasive procedures or active bleeding 3
• Give platelets for counts <10,000/mm³ or before invasive procedures 3
• Consider recombinant activated factor VII for invasive procedures 3

Infection Prevention and Management

Administer empirical broad-spectrum antibiotics immediately if there are signs of worsening encephalopathy or systemic inflammatory response syndrome—do NOT wait for culture results, as bacterial infections occur in 60-80% of ALF patients and fungal infections in one-third. 2

• Screen aggressively for infections and treat early 3
• Provide prophylaxis for stress ulceration with H2 blockers or proton pump inhibitors 3

Renal Support

If dialysis is needed, use continuous renal replacement therapy rather than intermittent hemodialysis. 3

• Avoid nephrotoxic agents 3
• For hepatorenal syndrome, treat with terlipressin and albumin (or norepinephrine if terlipressin unavailable) 3

Liver Transplantation Evaluation

Evaluate urgently for liver transplantation as this is often the only lifesaving option, particularly when transplant-free survival is <25%, with post-transplant survival rates of 80-90%. 2, 3

• King's College criteria remain the best prognostic tool, though sensitivity is limited (50-60%) 3
• Poor prognostic indicators include: idiosyncratic drug injury, non-hepatitis A viral infections, autoimmune hepatitis, mushroom poisoning, Wilson disease, Budd-Chiari syndrome, and indeterminate cause 3
• List patients early in the course of ALF, particularly those suitable for transplant 3

Common Pitfalls

• Do not rely on aminotransferase levels to assess prognosis—changes correlate poorly with outcomes 3
• Do not exclude acetaminophen toxicity based on low or absent levels—time of ingestion may be remote or unknown, especially with unintentional overdose over several days 1
• Consider malignant infiltration in patients with previous cancer history or massive hepatomegaly—this can mimic ALF 3
• Do not use systemic corticosteroids for general ALF treatment—they are only effective for autoimmune hepatitis 3