What is the management and treatment of acute liver failure?

Management and Treatment of Acute Liver Failure

Immediate Recognition 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 preexisting liver disease with illness duration ≤26 weeks) require immediate ICU or intermediate care unit admission for continuous monitoring of liver, kidney, brain, lung, coagulation, and circulation. 1

Hospital admission is mandatory when prothrombin time is prolonged by 4-6 seconds or more (INR ≥1.5) and there is any evidence of altered sensorium. 1

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Etiology-Specific Treatments

Acetaminophen Toxicity

For acetaminophen-induced ALF, 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, 2

• NAC should be given regardless of time since ingestion if acetaminophen toxicity is suspected 3, 2
• The total recommended intravenous dosage is 300 mg/kg given as 3 separate sequential doses over 21 hours 2
• Continue treatment if acetaminophen levels remain detectable or ALT/AST continue rising after the standard course 2

Viral Hepatitis

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

Autoimmune Hepatitis

• Consider liver biopsy to establish diagnosis 1, 3
• Treat with corticosteroids (prednisone 40-60 mg/day) 1, 3
• Place patients on the transplant list even while administering corticosteroids 1, 3

Wilson Disease

• Wilson disease-related ALF is uniformly fatal without transplantation 1
• Treatment to acutely lower serum copper should include albumin dialysis, continuous hemofiltration, plasmapheresis, or plasma exchange 1
• Do not use penicillamine in ALF due to hypersensitivity risk 1

Acute Fatty Liver of Pregnancy/HELLP Syndrome

• Consult obstetrical services and perform expeditious delivery 1, 3
• Recovery is typically rapid after delivery with supportive care as the only other treatment required 1

Drug-Induced Hepatotoxicity

• Discontinue all but essential medications 1
• Obtain detailed medication history including prescription drugs, non-prescription medications, herbs, and dietary supplements 1

Mushroom Poisoning

• Consider administration of penicillin G and silymarin 1
• List patients for transplantation as this is often the only lifesaving option 1

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Hemodynamic Support

Careful attention must be paid to fluid resuscitation and maintenance of adequate intravascular volume. 4, 1

• Use crystalloid fluids as first choice for fluid expansion 3
• Colloid (such as albumin) is preferred over crystalloid for ongoing resuscitation; all solutions should contain dextrose to maintain euglycemia 4
• Pulmonary artery catheterization should be considered in hemodynamically unstable patients to ensure appropriate volume replacement 4, 1
• If fluid replacement fails to maintain mean arterial pressure of 50-60 mm Hg, use systemic vasopressor support with epinephrine, norepinephrine, or dopamine (but not vasopressin) 4, 1, 3
• Norepinephrine is the vasopressor of choice for refractory hypotension 3, 5

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Central Nervous System Management

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, perform intubation for airway protection 1, 3
• Maintain serum sodium levels between 140-145 mmol/L to prevent cerebral edema 1, 3
• Control seizures with phenytoin; avoid benzodiazepines when possible 1, 3
• Lactulose may be considered to reduce ammonia levels, though evidence for improved outcomes is limited 1

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Coagulation Management

• Administer vitamin K to all patients with acute liver failure 1
• Reserve fresh frozen plasma (FFP) for invasive procedures or active bleeding only 1
• Give platelets for counts <10,000/mm³ or before invasive procedures 1
• Recombinant activated factor VII may be considered for invasive procedures 1

Common pitfall: Avoid routine transfusion of clotting factors to correct laboratory values in the absence of active bleeding, as this can obscure prognostic indicators and waste resources. 5

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Renal Support

If dialysis support is needed for acute renal failure, use continuous modes rather than intermittent hemodialysis. 4, 1

• Avoid nephrotoxic agents including NSAIDs 1, 5
• For hepatorenal syndrome, treat with terlipressin and albumin (or norepinephrine if terlipressin unavailable) 1

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Metabolic Management

• Manage hypoglycemia with continuous glucose infusions 4, 1
• Monitor and supplement phosphate, magnesium, and potassium levels as needed 4, 1
• Initiate enteral feedings early with moderate protein intake (approximately 60 grams per day) 4, 1
• Avoid severe protein restrictions; branched-chain amino acids have not been shown superior to other enteral preparations 4
• If enteral feedings are contraindicated, parenteral nutrition is an option despite risks of fungal infection 4, 1

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Infection Prevention and Management

• Provide prophylaxis for stress ulceration with H2 blockers or proton pump inhibitors 1
• Screen aggressively for infections and treat early, as bacterial infections are common precipitants 1
• Do not delay empirical antibiotics while awaiting culture results 5

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Liver Transplantation

Urgent hepatic transplantation is indicated in ALF where prognostic indicators suggest a high likelihood of death. 4, 1

• Contact transplant center early for patients with 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
• Post-transplant survival rates for ALF are as high as 80-90% 4, 1
• King's College criteria remain the best prognostic tool, though sensitivity is limited (50-60%) 1
• For acetaminophen-induced ALF, consider transplantation with 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

Critical pitfall: In the largest U.S. study, 10% of patients (1/4 of those listed for transplantation) died on the waiting list, emphasizing the importance of early listing. 4

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Respiratory Support

• Provide oxygen therapy and mechanical ventilation if respiratory failure develops 1
• Use protective ventilation settings per critical care guidelines 1
• Avoid high PEEP (>10 cmH₂O) due to risk of hepatic congestion 1

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Liver Support Systems

• Various liver support systems have been tested with no certain evidence of efficacy 1
• Plasmapheresis is indicated as bridging therapy until liver transplantation in Wilson disease patients 1
• Albumin dialysis (MARS) may stabilize patients with Wilson disease-related ALF 1
• Recent studies show improved short-term survival with porcine hepatocyte-based bioartificial liver, but further research is needed 1

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Special Consideration: Post-Cardiac Surgery ALF

For ischemic hepatic injury following cardiac surgery, cardiovascular support with aggressive hemodynamic management is the primary treatment, as liver transplantation is seldom indicated for this etiology. 5

• Maintain mean arterial pressure ≥50-60 mmHg through aggressive fluid resuscitation followed by vasopressor support 5
• Perform echocardiography immediately to assess cardiac function 5
• Aminotransferase levels will be markedly elevated initially but respond rapidly to stabilization of the circulatory problem 5
• Do not delay cardiovascular optimization while pursuing other therapies 5