What is the management approach for neonatal acute liver failure?

Management of Neonatal Acute Liver Failure

Neonatal acute liver failure requires immediate ICU admission with early contact to a pediatric liver transplant center, as liver transplantation is often the only life-saving option with long-term survival exceeding 60%, though many neonates will die on the waiting list without prompt referral. 1

Immediate Actions and Diagnostic Workup

ICU Admission and Transplant Referral

• Admit all neonates with suspected acute liver failure to an intensive care unit immediately upon recognition of coagulopathy (INR ≥1.5) and any degree of altered mental status 2
• Contact a pediatric liver transplant center within the first 2 days of presentation, as the "transplantation window" is narrow and early referral significantly reduces severity on admission 3, 2
• Note that hepatic encephalopathy is extremely difficult to diagnose and prove in neonates, unlike older children and adults 1

Essential Laboratory Evaluation

Obtain immediately 2:

• Prothrombin time/INR and complete blood count with ferritin levels
• Comprehensive metabolic panel including liver function tests (AST, ALT, alkaline phosphatase, total and direct bilirubin, albumin)
• Arterial blood gases and lactate
• Blood glucose monitoring at least every 2 hours
• Acetaminophen level and toxicology screen
• Viral hepatitis serologies (hepatitis A, B, C)
• Ceruloplasmin, 24-hour urine copper (for Wilson disease, though rare in neonates)
• Metabolic screening: amino acids, organic acids, acylcarnitine profile (metabolic causes account for 34.6% of cases under 2 years) 3

Imaging Studies

• Hepatic Doppler ultrasound to exclude vascular abnormalities and verify vessel patency 4
• Consider transjugular liver biopsy if etiology remains unclear after routine evaluation, as this can identify specific diagnoses that influence treatment 2

Etiology-Specific Management

Neonatal Hemochromatosis

• Neonatal hemochromatosis is the leading cause of liver failure in neonates, presenting within the first days of life 5
• Confirm diagnosis with MRI demonstrating iron deposition in non-reticuloendothelial organs or salivary gland biopsy showing siderosis 5
• Liver transplantation is the only effective treatment, though postoperative survival has historically been poor 5
• Treatment to acutely lower iron burden should include albumin dialysis, continuous hemofiltration, plasmapheresis, or plasma exchange 5, 2

Hemophagocytic Lymphohistiocytosis (HLH)

• HLH can present as acute liver failure in neonates, including preterm infants in the first days of life 5
• Recognition is critical as chemotherapy and bone marrow transplantation may reverse an otherwise fatal prognosis 5
• Liver transplantation is contraindicated in HLH due to high relapse risk in the transplanted organ 5
• Initiate HLH-directed chemotherapy protocol immediately upon diagnosis 5

Fatty Acid Oxidation Defects (FAOD)

• FAOD may present as recurrent episodes of acute liver failure with hypoketotic hypoglycemia and Reye-like syndrome 5
• Infants born to mothers with acute fatty liver of pregnancy or HELLP syndrome are at high risk 5
• First-line therapy is dietary management with intravenous glucose infusion of at least 10 mg/kg/min to maintain serum glucose above 100 mg/dL 5
• Prompt dietary intervention may reverse symptoms and preclude need for transplantation 5
• Consider liver transplantation only if recurrent episodes occur or medical therapy fails 5

Herpes Simplex Virus/Varicella Zoster

• Immediately place on transplant list and treat with acyclovir if herpes virus or varicella zoster is known or suspected 2

Metabolic Disorders (Tyrosinemia, Glycogen Storage Disease)

• Tyrosinemia type 1: Initiate NTBC (nitro-trifluoromethyl benzoyl cyclohexanedione) with dietary restriction of tyrosine and phenylalanine 5
• Transplantation required for incomplete response to NTBC or presence of hepatocellular carcinoma 5

Infectious Causes

• Viral hepatitis A and B require supportive care only, as no virus-specific treatment has proven effective 2
• Bacterial infections occur in 60-80% of acute liver failure patients; administer empirical broad-spectrum antibiotics immediately if signs of worsening clinical status or SIRS develop 6

Supportive Care Management

Hemodynamic Support

• Maintain mean arterial pressure ≥50-60 mmHg through aggressive fluid resuscitation first 2, 6
• Use colloid (albumin) rather than crystalloid as first-line, with all solutions containing dextrose to maintain euglycemia 2
• If fluid replacement fails, use epinephrine, norepinephrine, or dopamine—never use vasopressin 2

Metabolic Management

• Monitor blood glucose at least every 2 hours and manage hypoglycemia with continuous glucose infusions 2, 6
• Maintain serum sodium at 140-145 mmol/L to prevent cerebral edema 2
• Monitor and supplement phosphate, magnesium, and potassium levels as needed 2

Nutritional Support

• Initiate enteral feedings early with moderate protein intake (approximately 60 grams per day) 2
• Avoid severe protein restrictions—this outdated practice is not beneficial 2
• If enteral feeding is contraindicated, use parenteral nutrition despite increased risk of fungal infection 2

Coagulation Management

• Administer vitamin K to all patients 2
• Reserve fresh frozen plasma for active bleeding or invasive procedures only—do not give prophylactically 2, 6
• Transfuse platelets for counts <10,000/mm³ or before invasive procedures 2
• Consider recombinant activated factor VII for invasive procedures 2

Renal Support

• Avoid all nephrotoxic agents including NSAIDs 2
• If dialysis is needed, use continuous renal replacement therapy rather than intermittent hemodialysis 2, 6

Neurological Management

• Monitor mental status frequently; intubate for airway protection if encephalopathy progresses to grades III-IV 2
• Position with head elevated at 30 degrees and minimize stimulation 2
• Control seizures with phenytoin; avoid benzodiazepines when possible 2
• Use propofol for sedation due to favorable pharmacokinetics 2

Infection Prevention

• Provide stress ulcer prophylaxis with H2 blockers or proton pump inhibitors 2, 6
• Screen aggressively for infections and treat early, as bacterial infections are common precipitants 2
• Consider fungal infection if persistent fever despite antibacterial therapy 6

Liver Transplantation Decision-Making

Indications for Urgent Transplantation

• Urgent hepatic transplantation is indicated when prognostic indicators suggest high likelihood of death 2, 6
• Post-transplant survival rates for acute liver failure are 80-90% even in patients with multiple organ failures 2
• List patients early in the course of acute liver failure, as the transplantation window is narrow 2, 3

Poor Prognostic Indicators Requiring Transplant Listing

• 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
• Neonatal hemochromatosis 5

Contraindications to Transplantation

• Niemann-Pick disease type C (does not alter neurological disease progression) 5
• Hemophagocytic lymphohistiocytosis (high relapse risk in transplanted organ) 5
• Ischemic hepatic injury from cardiovascular causes (cardiovascular support is treatment of choice) 4

Critical Pitfalls to Avoid

• Do not delay transplant center contact—median referral time should be ≤2 days, not 7 days 3
• Do not wait for culture results before starting empirical antibiotics if clinical deterioration occurs 6
• Do not routinely correct coagulation abnormalities unless active bleeding is present 2, 6
• Do not restrict protein intake severely—this is an outdated practice 2
• Do not use vasopressin as a vasopressor in acute liver failure 2
• Do not delay diagnosis of metabolic disorders—up to 50% of pediatric acute liver failure cases have no identified cause, but metabolic causes are most common under 2 years of age 3, 7

Prognosis

• Overall mortality without liver transplantation is approximately 50% in pediatric acute liver failure 7
• Long-term survival after liver transplantation for neonatal acute liver failure exceeds 60% 1
• Many neonates will die on the waiting list without prompt referral and transplantation 1
• Some children will recover with appropriate supportive therapy without need for transplantation, particularly those with fatty acid oxidation defects or infectious causes 7, 5