What is the management and treatment of acute liver failure?

Management and Treatment of Acute Liver Failure

Immediate Recognition and Transfer

All patients with acute liver failure (ALF)—defined by coagulopathy (INR ≥1.5) and any degree of mental status alteration in patients without preexisting cirrhosis with illness duration ≤26 weeks—require immediate hospital admission and early contact with a liver transplant center. 1, 2

• Transfer to an ICU at a transplant center should occur as soon as possible, as this improves both transplant-free survival and access to emergency liver transplantation 3, 4
• Mental status must be monitored frequently, with ICU transfer if level of consciousness declines 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, 5
• NAC is indicated to prevent or lessen hepatic injury after ingestion of a potentially hepatotoxic quantity of acetaminophen 5
• Continue treatment beyond 21 hours if acetaminophen levels remain detectable or if ALT/AST continue rising 5

Viral Hepatitis

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

Autoimmune Hepatitis

• Consider transjugular liver biopsy to establish diagnosis 1, 2
• Treat with corticosteroids (prednisone 40-60 mg/day) AND simultaneously place on transplant list 1, 6

Wilson Disease

• Wilson disease-related ALF is uniformly fatal without transplantation 1, 6
• Acutely lower serum copper with albumin dialysis, continuous hemofiltration, plasmapheresis, or plasma exchange 1, 6
• Do NOT use penicillamine in acute setting due to hypersensitivity risk 1, 6

Mushroom Poisoning

• Administer penicillin G and silymarin/silibinin 1, 6
• List for transplantation immediately, as this is often the only lifesaving option 1, 6

Pregnancy-Related ALF

• For acute fatty liver of pregnancy or HELLP syndrome: consult obstetrics immediately and perform expeditious delivery 1, 6
• Recovery is typically rapid after delivery with supportive care only 1

Drug-Induced Liver Injury

• Discontinue all non-essential medications immediately 1, 6
• Obtain detailed medication history including prescription drugs, over-the-counter medications, herbs, and dietary supplements 1

Hemodynamic Management

Fluid Resuscitation

• Careful attention to fluid resuscitation and maintenance of adequate intravascular volume is essential 7, 1, 6
• Prefer colloid (albumin) over crystalloid; all solutions should contain dextrose to maintain euglycemia 7
• Consider pulmonary artery catheterization in hemodynamically unstable patients to guide volume replacement 7, 1, 2

Vasopressor Support

• If fluid replacement fails to maintain mean arterial pressure of 50-60 mm Hg, use epinephrine, norepinephrine, or dopamine (but NOT vasopressin) 7, 1, 2
• Dopamine has been associated with increased systemic oxygen delivery 7

Central Nervous System Management

Encephalopathy Monitoring

• Position patient with head elevated at 30 degrees and minimize stimulation 1
• For grades III-IV encephalopathy: intubate for airway protection 1, 2
• Maintain serum sodium between 140-145 mmol/L to prevent cerebral edema 2

Seizure Control

• Control seizures with phenytoin while avoiding benzodiazepines when possible 1, 2

Ammonia Management

• Lactulose may be considered to reduce ammonia levels, though evidence for improved outcomes is limited 1
• Early initiation of continuous renal replacement therapy (CRRT) to control hyperammonemia is now considered standard of care 3

Coagulation Management

• Administer vitamin K to all patients 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
• Consider recombinant activated factor VII for invasive procedures 1

Critical caveat: Avoid routine FFP administration as it obscures INR monitoring, which is essential for prognostication and transplant listing decisions 1

Renal Support

• If dialysis is needed for acute renal failure, use continuous modes rather than intermittent hemodialysis 7, 1, 6
• Avoid nephrotoxic agents 1, 6
• Continuous modes prevent rapid fluid shifts that can worsen cerebral edema 7

Metabolic Management

Glucose Control

• Manage hypoglycemia with continuous glucose infusions, as symptoms may be obscured by encephalopathy 7, 1

Electrolyte Replacement

• Phosphate, magnesium, and potassium levels frequently require repeated supplementation throughout hospital course 7, 1

Nutrition

• Initiate enteral feedings early 7, 1, 6
• Avoid severe protein restrictions; 60 grams per day is reasonable in most cases 7, 1
• Branched-chain amino acids have not shown superiority over other enteral preparations 7
• If enteral feeding is contraindicated, use parenteral nutrition despite increased fungal infection risk 7, 1

Infection Prevention

• Provide prophylaxis for stress ulceration with H2 blockers or proton pump inhibitors 1, 6
• Enteral and parenteral nutrition may reduce gastrointestinal bleeding risk 7
• Monitor closely for sepsis, as infection is a common complication 7

Liver Transplantation

Urgent hepatic transplantation is indicated when prognostic indicators suggest high likelihood of death 7, 1, 6

Poor Prognostic Indicators Requiring Early Transplant Listing:

• Idiosyncratic drug injury 1
• Non-hepatitis A viral infections 1
• Autoimmune hepatitis 1
• Mushroom poisoning 1
• Wilson disease 1
• Budd-Chiari syndrome 1
• Indeterminate cause 1

Transplant Outcomes

• Post-transplant survival rates are 80-90% 1, 6
• Spontaneous survival rates are approximately 40% 7
• Only 29% of patients receive a liver graft, while 10% die on the waiting list 7

Acetaminophen-Specific Transplant Criteria

• Arterial pH <7.3 after adequate volume resuscitation, OR 2
• PT >100 seconds with serum creatinine >3.4 mg/dL in patients with grade III/IV coma 2

Emerging Therapies

Plasma Exchange

• Plasma exchange may stabilize patients and serve as a bridge to transplantation 1, 3
• Particularly beneficial in Wilson disease to protect kidneys from copper-mediated tubular damage 1
• Recent evidence suggests improved short-term survival in some ALF patients 3, 4

Other Liver Support Systems

• Albumin dialysis (MARS) may stabilize patients but lacks definitive evidence for mortality benefit 1, 4
• Sorbent systems may transiently improve encephalopathy without long-term benefit 1
• Porcine hepatocyte-based bioartificial liver shows promise but requires further research 1

Common Pitfalls to Avoid

• Failing to contact transplant center early in the disease course 6
• Initiating penicillamine in acute Wilson disease (use plasmapheresis/dialysis instead) 1, 6
• Overlooking herbal preparations and dietary supplements as potential causes 6
• Delaying delivery in pregnancy-related liver failure 6
• Using intermittent hemodialysis instead of continuous modes 7, 1
• Routinely correcting coagulopathy with FFP, which obscures prognostic markers 1
• Failing to recognize malignant infiltration mimicking ALF in patients with cancer history 1