What is the management and treatment of acute liver failure?

Management and Treatment of Acute Liver Failure

Immediate Resuscitation and Stabilization

All patients with acute liver failure (ALF) require ICU admission for continuous monitoring of liver, kidney, brain, lung, coagulation, and circulation. 1

Hemodynamic Management

• Aggressive fluid resuscitation is the first priority, using colloid (albumin) rather than crystalloid solutions, with all fluids containing dextrose to maintain euglycemia. 2
• Pulmonary artery catheterization should be considered in hemodynamically unstable patients to guide volume replacement. 2, 1
• If fluid replacement fails to maintain mean arterial pressure of 50-60 mm Hg, initiate vasopressor support with norepinephrine, epinephrine, or dopamine (but never vasopressin). 2, 1
• Norepinephrine is the preferred vasopressor for refractory hypotension. 1, 3

Metabolic Management

• Administer continuous glucose infusions to prevent hypoglycemia, as symptoms are masked by encephalopathy. 2, 1
• Maintain serum sodium between 140-145 mmol/L to prevent cerebral edema. 1, 3
• Supplement phosphate, magnesium, and potassium levels repeatedly throughout the hospital course as they are frequently depleted. 2, 1

Renal Support

• If dialysis is required, use continuous renal replacement therapy rather than intermittent hemodialysis to avoid hemodynamic instability. 2, 1
• Avoid all nephrotoxic agents including NSAIDs. 1

Etiology-Specific Treatments

Acetaminophen Toxicity

• Administer N-acetylcysteine (NAC) immediately at 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, 4
• NAC is indicated to prevent or lessen hepatic injury after ingestion of a potentially hepatotoxic quantity of acetaminophen. 4
• Continue NAC if acetaminophen levels remain detectable or if ALT/AST continue rising after the standard 21-hour protocol. 4

Viral Hepatitis

• Hepatitis A and B require supportive care only, as no virus-specific treatment has proven effective. 1
• For suspected herpes simplex virus or varicella zoster, immediately place the patient on the transplant list and start acyclovir. 1, 3
• For patients requiring chemotherapy or immunosuppression with hepatitis B, administer nucleoside analogs prior to and for 6 months after treatment completion. 1

Autoimmune Hepatitis

• Consider transjugular liver biopsy to establish diagnosis. 1, 3
• Treat with corticosteroids (prednisone 40-60 mg/day) while simultaneously placing the patient on the transplant list. 1, 3

Wilson Disease

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

Acute Fatty Liver of Pregnancy/HELLP Syndrome

• Consult obstetrical services immediately and perform expeditious delivery. 1, 3
• 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 administration of penicillin G and silymarin. 1
• List for transplantation immediately as this is often the only lifesaving option. 1

Neurologic Management

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

Airway Protection

• For grades III-IV encephalopathy, perform endotracheal intubation for airway protection. 1, 3
• Use propofol for sedation due to favorable pharmacokinetics; avoid benzodiazepines as they worsen encephalopathy. 1, 3

Seizure Management

• Control seizures with phenytoin, adding diazepam only as needed. 1

Cerebral Edema Prevention

• Consider lactulose to reduce ammonia levels, though evidence for improved outcomes is limited. 1

Coagulation Management

• Administer vitamin K to all patients with ALF. 1
• Reserve fresh frozen plasma (FFP) for invasive procedures or active bleeding only, not for correcting laboratory values. 1
• Transfuse platelets for counts <10,000/mm³ or before invasive procedures. 1
• Consider recombinant activated factor VII for invasive procedures. 1

Infection Prevention and Management

• Screen aggressively for infections and treat early, as bacterial infections are the most common precipitant of deterioration. 1
• Administer prophylaxis for stress ulceration with H2 blockers or proton pump inhibitors. 1

Nutritional Support

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

Liver Transplantation

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

Poor Prognostic Indicators

• Idiosyncratic drug injury, non-hepatitis A viral infections, autoimmune hepatitis, mushroom poisoning, Wilson disease, Budd-Chiari syndrome, or indeterminate cause. 1, 3
• King's College criteria remain the best prognostic tool, though sensitivity is limited (50-60%). 1

Transplant Outcomes

• Post-transplant survival rates for ALF are 80-90%. 2, 1
• Contact transplant center early in the course of ALF, particularly for patients suitable for transplant. 1
• For acetaminophen-induced ALF, consider transplantation if arterial pH <7.3 after adequate volume resuscitation, or PT >100 seconds with serum creatinine >3.4 mg/dL in patients with grade III/IV coma. 3

Exception: Post-Cardiac Surgery ALF

• Ischemic hepatic injury from cardiac surgery rarely requires transplantation; aggressive hemodynamic management to restore hepatic perfusion is the definitive treatment. 5
• Aminotransferase levels respond rapidly to stabilization of the circulatory problem. 5

Critical Pitfalls to Avoid

• Do not delay cardiovascular optimization while pursuing other therapies in post-cardiac surgery ALF. 5
• Do not delay empirical antibiotics while awaiting culture results. 5
• Do not routinely transfuse clotting factors to correct laboratory values without active bleeding. 5
• Do not use nephrotoxic drugs including NSAIDs. 5
• Malignant infiltration of the liver can mimic ALF; consider this in patients with previous cancer history or massive hepatomegaly. 1

Liver Support Systems

• Various liver support systems (albumin dialysis, MARS, bioartificial liver) have been tested but lack certain evidence of efficacy for routine use. 1
• Plasmapheresis may serve as bridging therapy until transplantation, particularly in Wilson disease to protect kidneys from copper-mediated damage. 1