What is the management approach for acute liver failure?

Management of Acute Liver Failure

Immediate Recognition and Transfer

All patients with acute liver failure (ALF) must be admitted to an intensive care unit, and early transfer to a liver transplant center is mandatory to optimize outcomes, as transplant-free survival and emergency transplantation access are significantly improved at specialized centers. 1, 2, 3

• ALF is defined by coagulopathy (INR ≥1.5), any degree of hepatic encephalopathy, and illness duration ≤26 weeks in patients without preexisting liver disease 2, 4
• Contact a transplant center immediately when prothrombin time is prolonged by 4-6 seconds or more with any altered mental status 2
• Post-transplant survival rates reach 80-90%, while spontaneous survival is only 40% 1, 2

Etiology-Specific Treatment

Acetaminophen Toxicity

• Administer N-acetylcysteine (NAC) immediately at 140 mg/kg loading dose (oral/NG) followed by 70 mg/kg every 4 hours for 17 doses, even if >48 hours since ingestion 2, 5
• For IV administration: 300 mg/kg total dose given as three sequential infusions over 21 hours 5
• Continue NAC beyond 21 hours if acetaminophen levels remain detectable or ALT/AST continue rising 5

Viral Hepatitis

• Hepatitis A and B require supportive care only; no virus-specific treatment is effective 2
• For herpes simplex virus or varicella zoster: immediately list for transplant AND start acyclovir 2, 4
• Nucleoside analogs should be given to hepatitis B patients requiring chemotherapy/immunosuppression, continuing 6 months post-treatment 2

Autoimmune Hepatitis

• Obtain transjugular liver biopsy to confirm diagnosis 1, 2
• Start prednisone 40-60 mg/day immediately while simultaneously listing for transplantation 1, 2, 4
• Do not delay transplant listing despite corticosteroid therapy 1, 2

Wilson Disease

• Wilson disease-related ALF is uniformly fatal without transplantation 2
• Initiate albumin dialysis, continuous hemofiltration, plasmapheresis, or plasma exchange to lower serum copper and limit hemolysis 2
• Avoid penicillamine due to hypersensitivity risk 2

Acute Fatty Liver of Pregnancy/HELLP Syndrome

• Immediate obstetrical consultation and expeditious delivery are the definitive treatment 1, 2, 4
• Recovery is typically rapid after delivery with supportive care only 1, 2

Mushroom Poisoning

• Administer penicillin G and silymarin 2
• List immediately for transplantation as this is often the only lifesaving option 2

Drug-Induced Liver Injury

• Discontinue all non-essential medications immediately 2
• Obtain detailed medication history including prescription drugs, over-the-counter medications, herbs, and dietary supplements 2

Budd-Chiari Syndrome

• Confirm diagnosis with hepatic Doppler ultrasound, CT, or MR venography 1, 4
• Transplantation is indicated for hepatic failure, but exclude underlying malignancy first 1

Ischemic Hepatitis ("Shock Liver")

• Cardiovascular support is the primary treatment 1
• Transplantation is rarely indicated 1

Hemodynamic Management

Fluid Resuscitation

• Careful fluid resuscitation with colloid (albumin preferred) rather than crystalloid is essential; all solutions must contain dextrose to maintain euglycemia 1, 2
• Consider pulmonary artery catheterization in hemodynamically unstable patients to guide volume management 1, 2

Vasopressor Support

• If fluid replacement fails to maintain mean arterial pressure of 50-60 mm Hg, use norepinephrine, epinephrine, or dopamine (NOT vasopressin) 1, 2, 4
• Norepinephrine is the first-line vasopressor 4, 6
• Vasopressin may be added as second-line when increasing norepinephrine doses are required 6

Neurological Management

Encephalopathy Monitoring

• Monitor mental status frequently; transfer to ICU if level of consciousness declines 2
• Position patient with head elevated at 30 degrees and minimize stimulation 2

Airway Protection

• Intubate for grades III-IV encephalopathy for airway protection 2, 4
• Avoid benzodiazepines when possible 2, 4
• Control seizures with phenytoin 2

Cerebral Edema Prevention

• Maintain serum sodium 140-145 mmol/L 4
• Lactulose may be considered to reduce ammonia levels, though evidence for improved outcomes is limited 2

Coagulation Management

• Administer vitamin K to all patients 2
• Reserve fresh frozen plasma (FFP) for invasive procedures or active bleeding only 2
• Give platelets for counts <10,000/mm³ or before invasive procedures 2
• Consider recombinant activated factor VII for invasive procedures 2
• Provide daily pharmacologic thromboprophylaxis unless contraindicated 6

Renal Support

• If dialysis is needed, use continuous renal replacement therapy (CRRT) rather than intermittent hemodialysis 1, 2, 6, 3
• Avoid nephrotoxic agents 2, 6
• CRRT helps control hyperammonaemia and is now considered standard of care 3

Metabolic Management

Glucose Control

• Manage hypoglycemia with continuous glucose infusions; symptoms may be obscured by encephalopathy 1, 2
• Target blood glucose ≤180 mg/dL with protocolized approach 6

Electrolyte Management

• Monitor and supplement phosphate, magnesium, and potassium frequently throughout hospitalization 1, 2, 6

Nutrition

• Initiate enteral feedings early with approximately 60 grams protein per day 1, 2, 6
• Avoid severe protein restriction 1
• Branched-chain amino acids are not superior to standard enteral preparations 1
• If enteral feeding is contraindicated, use parenteral nutrition despite increased fungal infection risk 1, 2

Infection Prevention and Management

• Administer empiric broad-spectrum antibiotics within 1 hour of identifying sepsis 6
• Use third-generation cephalosporins, piperacillin-tazobactam, or fluoroquinolones for empiric coverage 6
• Obtain blood cultures before antibiotics, but do not delay administration 6
• Perform periodic surveillance cultures to detect bacterial and fungal infections early 6
• Consider fungal infections in patients not responding to antibiotics, especially with prolonged hospitalization 6
• Provide stress ulcer prophylaxis with H2 blockers or proton pump inhibitors 2

Transplantation Criteria

Urgent hepatic transplantation is indicated when prognostic indicators suggest high likelihood of death 1, 2, 4

Poor Prognostic Indicators

• Idiosyncratic drug injury 2
• Non-hepatitis A viral infections 2
• Autoimmune hepatitis 2
• Mushroom poisoning 2
• Wilson disease 2
• Budd-Chiari syndrome 2
• Indeterminate cause 2

Acetaminophen-Specific Transplant Criteria

• Arterial pH <7.3 after adequate volume resuscitation 4
• PT >100 seconds with serum creatinine >3.4 mg/dL in patients with grade III/IV coma 4

Emerging Therapies

• Plasma exchange may stabilize patients and serve as bridge to transplantation, particularly in Wilson disease 2, 3
• Molecular Adsorbents Recirculating System (MARS) may be efficacious as alternative to plasmapheresis 2
• Bioartificial liver devices show promise for short-term survival improvement but require further research 2

Critical Pitfalls to Avoid

• Do not use vasopressin as a vasopressor in ALF 1, 2
• Do not give FFP prophylactically; it obscures coagulation monitoring and wastes resources 2
• Do not use intermittent hemodialysis; continuous modes are mandatory 1, 2
• Do not restrict protein severely; 60 grams/day is appropriate 1
• Do not delay NAC administration for acetaminophen toxicity, even if >48 hours post-ingestion 2, 5
• Do not delay transplant listing while attempting medical therapy in poor prognosis etiologies 2, 4
• Systemic corticosteroids are ineffective for general ALF treatment except in autoimmune hepatitis 2
• Changes in aminotransferase levels correlate poorly with prognosis 2