What is the initial management for a patient with acute liver failure?

Initial Management of Acute Liver Failure

All patients with acute liver failure (defined as INR ≥1.5 with any degree of encephalopathy in a patient without pre-existing liver disease) must be immediately admitted to an intensive care unit and a liver transplant center should be contacted urgently, as the transplantation window is often narrow. 1, 2

Immediate Diagnostic Workup

Upon recognition of ALF, obtain the following laboratory tests immediately:

• Prothrombin time/INR to confirm coagulopathy (INR ≥1.5) 1, 2
• Acetaminophen level regardless of history, as this is the most common cause and treatable 3, 1
• Comprehensive metabolic panel including liver enzymes (AST, ALT, alkaline phosphatase, bilirubin), electrolytes, glucose, creatinine, and BUN 1, 2
• Arterial blood gas and lactate to assess acid-base status and tissue perfusion 1
• Complete blood count to evaluate for cytopenias 1
• Viral hepatitis serologies (hepatitis A, B, C, E) 3, 1
• Toxicology screen for drug-induced causes 1
• Ceruloplasmin and 24-hour urine copper if patient is <40 years old to evaluate for Wilson disease 1, 2
• Autoimmune markers (ANA, ASMA, IgG) if autoimmune hepatitis suspected 1
• Ammonia level to assess severity of hepatic encephalopathy 3

Perform Doppler ultrasound of the liver immediately to exclude chronic liver disease (ascites, dysmorphic liver), verify vascular patency (hepatic veins, portal vein for Budd-Chiari syndrome), and rule out malignant infiltration 3, 2. Obtain echocardiography if ischemic hepatitis is suspected (elderly, cardiac history, AST >> ALT) 3.

Universal Pharmacologic Treatment: N-Acetylcysteine

Administer N-acetylcysteine (NAC) immediately to ALL patients with acute liver failure, regardless of etiology or time since presentation. 3, 1, 2

Dosing Regimen

• Loading dose: 140 mg/kg orally or via nasogastric tube, OR 150 mg/kg IV over 1 hour 1, 4
• Maintenance dose: 70 mg/kg every 4 hours for 17 doses (oral), OR IV protocol with 50 mg/kg over 4 hours, then 100 mg/kg over 16 hours 1, 4
• Continue NAC even if >48 hours since acetaminophen ingestion 1

The evidence strongly supports NAC use beyond acetaminophen toxicity: in non-acetaminophen ALF, NAC improves overall survival (76% vs 59%) and transplant-free survival (64% vs 26%) 3. For acetaminophen-induced ALF specifically, NAC reduces progression to grade III-IV encephalopathy (51% vs 75%) and mortality (37% vs 63%) 3.

Etiology-Specific Treatments

Acetaminophen Overdose

• Activated charcoal (1 g/kg orally) if presentation within 4 hours of ingestion, given just prior to NAC 1
• Continue NAC as above 3, 1

Autoimmune Hepatitis

• Consider transjugular liver biopsy to confirm diagnosis 3, 1, 2
• Prednisone 40-60 mg/day immediately 3, 1, 2
• List for transplantation even while administering corticosteroids, as response is unpredictable 3, 1

Herpes Simplex Virus or Varicella Zoster

• Acyclovir immediately if suspected 1, 2
• Immediate transplant listing as these are uniformly fatal without intervention 1

Wilson Disease

• Immediate transplant listing as this is uniformly fatal without transplantation 1
• Plasmapheresis, albumin dialysis, continuous hemofiltration, or plasma exchange to acutely lower serum copper and limit hemolysis 1, 2
• Do NOT use penicillamine due to hypersensitivity risk 1

Acute Fatty Liver of Pregnancy/HELLP Syndrome

• Immediate obstetrical consultation and expeditious delivery 3, 1, 2
• 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 (Amanita)

• Consider penicillin G and silymarin 1
• Immediate transplant listing as this is often the only lifesaving option 1

Critical Supportive Care Measures

Hemodynamic Management

Maintain mean arterial pressure ≥50-60 mmHg through the following stepwise approach 3, 1, 2:

1. Aggressive fluid resuscitation with colloid (albumin) preferred over crystalloid 1, 2
2. All IV solutions should contain dextrose to maintain euglycemia 2
3. If fluid replacement fails, use vasopressors: epinephrine, norepinephrine, or dopamine (NOT vasopressin) 3, 1, 2
4. Consider pulmonary artery catheterization in hemodynamically unstable patients to guide therapy 1

Neurologic 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
• Intubate for airway protection if Glasgow Coma Score <8 or grade III-IV encephalopathy 3, 1
• Maintain serum sodium 140-145 mmol/L; hypertonic saline can decrease intracranial pressure 2
• Use propofol for sedation due to favorable pharmacokinetics; avoid benzodiazepines as they worsen encephalopathy 3, 1, 2
• Avoid dexmedetomidine due to exclusive hepatic metabolism 3
• Control seizures with phenytoin, adding diazepam only as needed 1
• Consider lactulose to reduce ammonia levels, though evidence for improved outcomes is limited 1

Important caveat: ICP monitoring devices have been associated with hemorrhagic complications in 7-20% of ALF cases and have not demonstrated mortality benefit 3. Transcranial Doppler ultrasound is a safer first-line monitoring tool 3.

Coagulation Management

• Administer vitamin K to all patients 1
• Reserve fresh frozen plasma (FFP) for active bleeding or invasive procedures only—do NOT give prophylactically 3, 1, 2
• Most ALF patients have rebalanced hemostasis; bleeding complications occur in only 10% 3
• Give platelets for counts <10,000/mm³ or before invasive procedures 1
• Consider recombinant activated factor VII for invasive procedures 1

Renal Management

• Avoid nephrotoxic agents (aminoglycosides, NSAIDs, vancomycin) 5
• If dialysis needed, use continuous renal replacement therapy (CRRT) rather than intermittent hemodialysis 3, 1, 2
• Monitor regional citrate anticoagulation carefully due to potential metabolic effects 2

Metabolic Management

• Monitor blood glucose at least every 2 hours 2
• Manage hypoglycemia with continuous glucose infusions 1, 2
• Monitor and supplement phosphate, magnesium, and potassium as needed 1

Nutritional Support

• Initiate enteral feedings early with moderate protein intake (approximately 60 grams per day) 1, 2
• Avoid severe protein restrictions—they are not beneficial 2
• Branched-chain amino acids have not shown superiority over standard enteral preparations 2
• If enteral feeding contraindicated, use parenteral nutrition despite increased fungal infection risk 1

Infection Prevention

• Prophylaxis for stress ulceration with H2 blockers or proton pump inhibitors 1
• Screen aggressively for infections as bacterial infections occur in 60-80% of ALF patients 5
• Initiate empirical broad-spectrum antibiotics (such as piperacillin-tazobactam) immediately if signs of sepsis or worsening encephalopathy 5

Respiratory Management

• Use protective mechanical ventilation settings per critical care guidelines 3, 1
• Avoid high PEEP (>10 cmH₂O) due to risk of hepatic congestion 3, 1

Liver Transplantation Considerations

Contact transplant center immediately upon diagnosis, as the window for transplantation is narrow 1, 2. Urgent hepatic transplantation is indicated when prognostic indicators suggest high likelihood of death 1, 2. Post-transplant survival rates reach 80-90% even in patients with multiple organ failures 2.

King's College Criteria remain the best prognostic tool (though sensitivity is limited at 50-60%) 1, 2:

• For acetaminophen-induced ALF: pH <7.3, OR PT >100 seconds (INR >6.5), OR creatinine >3.4 mg/dL with grade III-IV encephalopathy
• For non-acetaminophen ALF: PT >100 seconds (INR >6.5), OR any 3 of: age <10 or >40 years, non-A/non-B hepatitis, drug reaction, jaundice >7 days before encephalopathy, PT >50 seconds, bilirubin >17.5 mg/dL

Common Pitfalls to Avoid

• Do NOT delay NAC administration while waiting for acetaminophen levels or etiology determination 3, 1
• Do NOT use systemic corticosteroids for general ALF treatment except in confirmed autoimmune hepatitis 1, 2
• Do NOT give prophylactic FFP or coagulation factors—this precludes assessment of disease progression and most patients have rebalanced hemostasis 3, 2
• Do NOT use vasopressin for hemodynamic support in ALF 1, 2
• Do NOT use benzodiazepines for sedation as they worsen encephalopathy 3, 1