What is the treatment for acute liver failure?

Treatment of Acute Liver Failure

Immediate Etiology-Specific Treatment

For acetaminophen-induced ALF, immediately administer N-acetylcysteine (140 mg/kg orally or via nasogastric tube, followed by 70 mg/kg every 4 hours for 17 doses) even if more than 48 hours have elapsed since ingestion. 1, 2 This is the only FDA-approved specific therapy and should be given in the emergency room without delay. 2, 3 Emerging evidence suggests N-acetylcysteine may benefit non-acetaminophen ALF cases, with usage increasing from 15.8% to 49.4% in these patients between study periods. 4

Other Etiology-Specific Interventions

Viral Hepatitis:

• Hepatitis A and B require supportive care only, as no virus-specific treatment improves outcomes. 1
• For herpes simplex virus or varicella zoster ALF, immediately list for transplant and start acyclovir. 1

Wilson Disease:

• Uniformly fatal without transplantation. 1
• Initiate albumin dialysis, continuous hemofiltration, plasmapheresis, or plasma exchange to lower serum copper and limit hemolysis. 1
• Avoid penicillamine due to hypersensitivity risk. 1

Autoimmune Hepatitis:

• Consider liver biopsy for diagnosis. 1
• Treat with prednisone 40-60 mg/day while simultaneously listing for transplant. 1

Acute Fatty Liver of Pregnancy/HELLP:

• Expeditious delivery is the definitive treatment; recovery is typically rapid afterward with supportive care only. 1

Drug-Induced Hepatotoxicity:

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

Mushroom Poisoning:

• Administer penicillin G and silymarin. 1
• List for transplant immediately as this is often the only lifesaving option. 1

Intensive Care Unit Management

All patients with ALF require ICU or intermediate care unit admission for continuous monitoring of liver, kidney, brain, lung, coagulation, and circulation. 5

Hemodynamic Support

• Maintain adequate intravascular volume with careful fluid resuscitation. 1
• Consider pulmonary artery catheterization in hemodynamically unstable patients. 1
• Target mean arterial pressure of 50-60 mm Hg using vasopressors (epinephrine, norepinephrine, or dopamine—not vasopressin) if fluid replacement fails. 1
• Crystalloid fluids are first choice for volume expansion. 6
• Norepinephrine is the preferred vasopressor for refractory hypotension. 5, 6

Neurological Management

For hepatic encephalopathy grades III-IV, intubate for airway protection. 1

• Position head elevated at 30 degrees and minimize stimulation. 1
• Avoid benzodiazepines as they worsen encephalopathy. 5, 1
• Use propofol for sedation due to favorable pharmacokinetics. 1, 3
• Avoid dexmedetomidine due to exclusive hepatic metabolism. 5
• Control seizures with phenytoin, adding diazepam only as needed. 3
• Consider lactulose to reduce ammonia levels, though evidence for improved outcomes is limited. 1
• Intracranial pressure monitoring may be considered in high-grade encephalopathy, though observational data show no mortality difference with routine monitoring. 5

Metabolic Management

• Monitor glucose continuously (at least every 2 hours) and manage hypoglycemia with continuous glucose infusions. 1, 6
• Maintain serum sodium between 140-145 mmol/L. 6
• Monitor and supplement phosphate, magnesium, and potassium as needed. 1
• Initiate early enteral feeding with moderate protein intake (approximately 60 grams per day). 1, 3
• Use parenteral nutrition only if enteral feeding is contraindicated, despite increased fungal infection risk. 1

Coagulation Management

• Administer vitamin K to all patients. 1
• Reserve fresh frozen plasma for invasive procedures or active bleeding only—do not routinely correct coagulation abnormalities. 1, 6
• Give platelets for counts <10,000/mm³ or before invasive procedures. 1
• Consider recombinant activated factor VII for invasive procedures. 1

Renal Support

• Avoid nephrotoxic agents including NSAIDs. 1, 6
• Use continuous renal replacement therapy rather than intermittent hemodialysis if dialysis is needed. 1, 6
• For hepatorenal syndrome, treat with terlipressin and albumin (or norepinephrine if terlipressin unavailable). 5, 6
• Administer volume expansion with albumin for suspected acute tubular necrosis in the setting of spontaneous bacterial peritonitis. 5

Infection Prevention and Management

• Screen aggressively for infections and treat early, as bacterial infections are common precipitants. 5, 3
• Initiate prophylactic broad-spectrum antibiotics and antifungal agents. 3
• Provide stress ulcer prophylaxis with H2 blockers or proton pump inhibitors. 1

Respiratory Support

• Provide oxygen therapy and mechanical ventilation if respiratory failure develops. 5
• Use protective ventilation settings per critical care guidelines. 5
• Avoid high PEEP (>10 cmH₂O) due to risk of hepatic congestion. 5

Liver Support Systems

Extracorporeal liver support systems (albumin dialysis/MARS, Prometheus) do not improve survival in ACLF and should not be routinely recommended. 5 However, these systems may stabilize patients as a bridge to transplantation in specific cases like Wilson disease. 1 Bioartificial liver devices show promise in short-term survival improvement but require further research. 1

Liver Transplantation

Urgent liver transplantation is indicated when prognostic indicators suggest high likelihood of death, with post-transplant survival rates of 80-90%. 1

• List patients early in the course of ALF, particularly those suitable for transplant. 5
• 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
• King's College criteria remain the best prognostic tool, though sensitivity is limited (50-60%). 5
• For ACLF-3 with organ failures ≥4 or CLIF-C ACLFs >64 at days 3-7, discontinue intensive support if transplant is contraindicated or unavailable due to futility. 5

Key Monitoring Parameters

• Prothrombin time/INR, comprehensive metabolic panel, arterial blood gases, lactate. 1
• Arterial ammonia levels (risk of intracranial hypertension when sustained at 150-200 mmol/L). 5
• Mental status assessment frequently using standardized scales. 6
• Coagulation parameters, complete blood counts, and metabolic panels frequently. 6