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 the diagnosis is suspected, as this improves both transplant-free survival and access to emergency liver transplantation 1, 3
• Mental status must be assessed frequently, with ICU transfer mandatory 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, 4
• NAC should be given regardless of time elapsed since ingestion in all suspected cases 2, 4

Viral Hepatitis

• Hepatitis A and B require supportive care only, as no virus-specific treatment has proven effective 1, 5
• For herpes simplex virus or varicella zoster: immediately administer acyclovir AND place patient on transplant list 1, 5
• For hepatitis B patients requiring chemotherapy/immunosuppression: give nucleoside analogs prior to and continue for 6 months after treatment completion 1, 5

Autoimmune Hepatitis

• Obtain liver biopsy to establish diagnosis when suspected 1, 2
• Treat with prednisone 40-60 mg/day AND simultaneously place on transplant list 1, 2, 5

Wilson Disease

• Wilson disease-related ALF is uniformly fatal without transplantation 1, 5
• Immediately initiate albumin dialysis, continuous hemofiltration, plasmapheresis, or plasma exchange to lower serum copper 1, 5
• Do NOT use penicillamine in acute setting due to hypersensitivity risk 1, 5

Pregnancy-Related ALF

• For acute fatty liver of pregnancy/HELLP syndrome: consult obstetrics immediately and perform expeditious delivery 1, 2, 5
• Recovery is typically rapid after delivery with supportive care only 1

Drug-Induced Liver Injury

• Discontinue all non-essential medications immediately 1, 5
• Obtain detailed medication history including prescription drugs, over-the-counter medications, herbs, and dietary supplements 1

Mushroom Poisoning

• Administer penicillin G and silymarin/silibinin 1, 5
• List for transplantation immediately as this is often the only lifesaving option 1, 5

Hemodynamic Management

Fluid Resuscitation

• Careful attention to fluid resuscitation and maintenance of adequate intravascular volume is essential 6, 1, 5
• Prefer colloid (albumin) over crystalloid solutions; all solutions should contain dextrose to maintain euglycemia 6
• Consider pulmonary artery catheterization in hemodynamically unstable patients to guide volume replacement 6, 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) 6, 1, 2, 5

Neurological Management

Encephalopathy Monitoring

• Monitor mental status frequently with progression from grade I-II (confusion, drowsiness) to grade III-IV (stupor, coma) 1
• Position patient with head elevated at 30 degrees and minimize stimulation 1

Airway Protection

• Perform endotracheal intubation for grades III-IV encephalopathy to protect airway 1, 2
• Control seizures with phenytoin; avoid benzodiazepines when possible 1, 2

Ammonia Management

• Consider lactulose administration to reduce ammonia levels, though evidence for improved outcomes is limited 1
• Maintain serum sodium between 140-145 mmol/L to prevent cerebral edema 2

Metabolic Management

Glucose Control

• Manage hypoglycemia with continuous glucose infusions, as symptoms may be obscured by encephalopathy 6, 1, 5

Electrolyte Replacement

• Monitor and supplement phosphate, magnesium, and potassium levels frequently throughout hospital course 6, 1, 5

Nutrition

• Initiate enteral feedings early with moderate protein intake (approximately 60 grams per day); avoid severe protein restriction 6, 1, 5
• Branched-chain amino acids have not shown superiority over standard enteral preparations 6
• If enteral feeding contraindicated (e.g., severe pancreatitis), use parenteral nutrition despite increased fungal infection risk 6, 1

Coagulation Management

• Administer vitamin K to all patients 1
• Reserve fresh frozen plasma (FFP) for invasive procedures or active bleeding only, NOT for prophylactic correction of INR 1
• Give platelets for counts <10,000/mm³ or before invasive procedures 1
• Consider recombinant activated factor VII for invasive procedures 1

Renal Support

• If dialysis needed for acute renal failure, use continuous modes rather than intermittent hemodialysis 6, 1, 2, 5
• Avoid nephrotoxic agents 1, 5
• Early initiation of continuous renal replacement therapy (CRRT) to control hyperammonemia is now considered standard of care 3

Infection Prevention

• Provide prophylaxis for stress ulceration with H2 blockers or proton pump inhibitors 1
• Monitor closely for infections and sepsis, as these are common complications 6, 7

Liver Transplantation

Indications

• Urgent hepatic transplantation is indicated when prognostic indicators suggest high likelihood of death 6, 1, 2, 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

Outcomes

• Post-transplant survival rates are 80-90% 1, 5
• Spontaneous survival rates are approximately 40% with current medical management 6

Acetaminophen-Specific Transplant Criteria

• Consider transplantation if 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 2

Emerging Therapies

Plasma Exchange

• Therapeutic plasma exchange may stabilize the sickest ALF patients and serve as bridge to transplantation 1, 3, 8
• Particularly useful in Wilson disease to protect kidneys from copper-mediated tubular damage 1

Liver Support Systems

• Various artificial liver support systems have been tested without certain evidence of efficacy 1
• Sorbent systems may show transient improvement in hepatic encephalopathy but no long-term benefit 1

Critical Pitfalls to Avoid

• Delaying contact with transplant center—this must occur immediately upon diagnosis 1, 3
• Withholding NAC in acetaminophen toxicity due to time elapsed since ingestion 1, 4
• Using penicillamine in acute Wilson disease 1, 5
• Delaying delivery in pregnancy-related liver failure 5
• Prophylactically correcting INR with FFP, which can obscure prognostic markers 1
• Overlooking herbal preparations and dietary supplements as potential causes 5