What are the treatment guidelines for liver failure in a neonate?

Management of Neonatal Liver Failure

Liver transplantation is the only effective treatment for neonatal liver failure when supportive or disease-specific therapies fail, and urgent evaluation at a pediatric liver transplant center should be initiated immediately upon diagnosis. 1

Immediate Recognition and Referral

• Immediate contact with a pediatric liver transplant center is mandatory for neonates presenting with acute liver failure or acute decompensation of established liver disease. 1
• Neonatal liver failure is defined as failure of hepatic synthetic function within the first 4 weeks of life, with coagulopathy being the main diagnostic finding following vitamin K administration. 2, 3
• Encephalopathy is not essential for diagnosis in neonates, unlike older children and adults. 2
• The condition carries a mortality rate of 55-70% without transplantation, making early recognition critical. 3

Initial Diagnostic Workup and Stabilization

Critical Laboratory Assessment

• Obtain fractionated bilirubin (conjugated vs unconjugated), complete blood count, liver function tests (ALT, AST, alkaline phosphatase, GGT, albumin), and prothrombin time/INR to evaluate synthetic function. 4, 5
• Check serum ammonia levels, as the liver plays a critical role in removing ammonia and other metabolic waste products. 6
• Measure alpha-fetoprotein levels, as elevated or rising values may indicate hepatocellular carcinoma risk. 1
• Assess for coagulopathy through INR/PT, which reflects impaired synthesis of clotting factors II, VII, IX, X, and factor V. 4

Immediate Empiric Treatment (While Awaiting Etiology)

• Administer acyclovir immediately until herpes simplex virus infection is excluded, as this is a life-saving intervention. 3
• Initiate lactose-free feeding until galactosemia is excluded. 3
• Administer vitamin K to correct coagulopathy; uncorrectable coagulopathy despite vitamin K indicates severe hepatocellular dysfunction requiring urgent transplant evaluation. 4, 5
• Monitor for and manage complications including hypoglycemia, coagulopathy, encephalopathy, ascites, and infection. 4

Etiology-Specific Diagnosis and Management

Neonatal Hemochromatosis (Leading Cause)

• Neonatal hemochromatosis is the leading cause of liver failure in neonates, with infants typically presenting within the first few days of life. 1
• Diagnosis requires demonstration of marked iron elevation in non-reticuloendothelial organs via MRI or detection of siderosis in salivary glands. 1
• Liver transplantation is the only effective treatment for severe neonatal hemochromatosis, as postoperative survival has historically been poor but remains the sole definitive option. 1
• Urgent evaluation at a transplant center is recommended immediately upon diagnosis. 1

Viral Infections

• Herpes simplex virus, cytomegalovirus, and other viral infections are common causes requiring specific antiviral therapy. 2, 3
• Continue acyclovir until HSV is definitively excluded. 3

Metabolic Diseases

Tyrosinemia Type 1:

• Presents with systemic illness and liver dysfunction in infants a few months old, with cirrhosis and HCC common at diagnosis. 1
• Treat with dietary restriction of tyrosine and phenylalanine plus NTBC (nitro-trifluoromethyl benzoyl cyclohexanedione) to reduce toxic metabolite formation. 1
• Transplantation is required for incomplete response to medical management or presence of HCC. 1

Urea Cycle Defects:

• Present within hours to days after birth with catastrophic illness: poor feeding, lethargy, vomiting, tachypnea, progressing to coma. 1
• Hyperammonemic crises cause devastating neurological outcomes and are triggered by catabolic events or protein overload. 1
• Urgent referral for liver transplantation should be considered when patients present in the first year of life with severe urea cycle defects to prevent irreversible neurological damage. 1
• Living related liver donation may be an option after confirming donor phenotype. 1

Crigler-Najjar Type I:

• Presents with marked unconjugated hyperbilirubinemia (>20 mg/dL) during the neonatal period, unresponsive to phenobarbital. 5, 7
• Initial treatment consists of exchange transfusions to prevent kernicterus. 7
• Long-term management requires intensive phototherapy (20-24 hours daily during crises, minimum 8-12 hours daily for maintenance). 7
• Referral for liver transplant evaluation should occur at the time of diagnosis before brain damage develops, as transplantation is the only definitive treatment. 1, 7

Galactosemia:

• Maintain lactose-free feeding until excluded. 3

Hemophagocytic Lymphohistiocytosis (HLH)

• HLH presenting as acute liver failure in neonates requires recognition, as chemotherapy and bone marrow transplantation may reverse the otherwise unfavorable prognosis. 1
• Liver transplantation is contraindicated given the high relapse risk in the transplanted organ. 1
• Most cases (80%) of familial HLH occur within the first year of life, with some presenting in the first days or even in preterm infants. 1

Supportive Care and Monitoring

Nutritional Management

• Address hypermetabolism, which increases caloric requirements by 20-80% above normal in chronic liver disease. 4
• Manage malabsorption of fats and fat-soluble vitamins (A, D, E, K) due to cholestasis and reduced bile acid secretion. 4
• Monitor for failure to thrive and poor weight gain despite adequate caloric intake. 1, 4

Complication Management

• Monitor for and treat ascites resulting from portal hypertension, vasodilation, hyperaldosteronism, and hypoalbuminemia. 4
• Assess for variceal hemorrhage, a life-threatening complication of portal hypertension. 1, 4
• Monitor for hepatorenal syndrome from renal vasoconstriction and hepatopulmonary syndrome from intrapulmonary vascular dilatations. 4
• Watch for progression of hepatic encephalopathy, which indicates deteriorating function requiring urgent transplant evaluation. 1, 4

Liver Transplantation Evaluation

Indications for Urgent Transplant Evaluation

• Neonatal hemochromatosis with severe liver failure. 1
• Crigler-Najjar Type I at time of diagnosis. 1, 7
• Severe urea cycle defects presenting in the first year of life. 1
• Tyrosinemia with HCC or incomplete response to NTBC and dietary management. 1
• Progressive liver failure unresponsive to disease-specific therapy. 1

Multidisciplinary Transplant Team

• The evaluation requires a comprehensive multidisciplinary team including hepatologist, transplant surgeon, anesthesiologist, social worker, psychologist, dietician, pharmacist, and transplant coordinator. 1
• Preoperative assessment must identify extrahepatic complications that may compromise survival and quality of life after transplantation. 1

Critical Pitfalls to Avoid

• Do not delay acyclovir administration while awaiting HSV testing results. 3
• Do not delay lactose-free feeding while awaiting galactosemia results. 3
• Do not attribute coagulopathy solely to liver disease before administering vitamin K. 4, 5
• Do not delay referral to a pediatric liver transplant center once neonatal liver failure is identified. 1
• Recognize that toxic bilirubin accumulation in lungs can cause yellow hyaline membrane deposition, leading to hypoxia and precipitating further ischemic liver injury. 8
• Be aware that up to 50% of children with acute liver failure will never have an underlying cause identified, but this should not delay supportive care and transplant evaluation. 9