In a neonate or young infant, especially with a large patent ductus arteriosus, severe sepsis, metabolic disease, or congenital liver anomaly, how can I recognize acute liver failure?

Recognizing Acute Liver Failure in Neonates and Young Infants

Acute liver failure in a baby is identified primarily by the presence of coagulopathy (prolonged PT/INR) that persists after vitamin K administration, even when transaminases or bilirubin levels appear near normal or only mildly elevated. 1, 2

Critical Diagnostic Features

Primary Laboratory Indicators

• Coagulopathy is the cardinal finding: Prothrombin time (PT/INR) prolongation after vitamin K administration defines acute liver failure in infants, as loss of >70% of hepatic synthetic function produces clinically significant coagulopathy 3, 2, 4

• Transaminases can be misleadingly normal: In neonatal hemochromatosis and tyrosinemia, transaminases may be low or near normal despite severe liver failure, whereas hypoxic-ischemic injury and infections typically produce markedly elevated transaminases 1, 5

• Conjugated hyperbilirubinemia >25 μmol/L requires urgent referral: Any neonate with conjugated bilirubin exceeding this threshold needs immediate pediatric assessment for liver disease 3

• Jaundice may be absent: Up to 24% of infants with acute liver failure present without visible jaundice, making coagulopathy screening essential in any sick neonate 1

Clinical Presentation Patterns

High-risk scenarios demanding immediate evaluation:

• Sepsis with coagulopathy: Severe infection can precipitate acute liver failure through direct hepatocellular injury 1, 2

• Large patent ductus arteriosus with poor perfusion: Hypoxic-ischemic insult accounts for 19% of neonatal acute liver failure cases and produces elevated transaminases with coagulopathy 1

• Failure to thrive with hepatomegaly: Progressive hepatosplenomegaly, ascites, and synthetic dysfunction suggest metabolic disease (36% of cases) or alpha-1 antitrypsin deficiency 3, 1

• Acholic stools with dark urine: Biliary atresia represents 50% of neonatal cholestasis and requires surgical intervention before 60 days of age 6

Essential Immediate Workup

Obtain these tests urgently in any infant with suspected liver failure:

• Fractionated bilirubin (total and conjugated)
• Complete blood count with platelet count
• PT/INR and PTT after vitamin K administration
• Serum transaminases (AST, ALT)
• Albumin
• Blood glucose 3, 6, 1

Thrombocytopenia indicates advanced disease: Low platelets result from decreased production, splenic sequestration, and increased destruction in severe liver injury 3

Etiology-Specific Recognition Patterns

Metabolic Disease (36% of cases)

• Tyrosinemia Type 1: Elevated AFP (often 10-fold above normal neonatal range), coagulopathy appearing before other hepatic signs, and systemic illness; diagnosis requires elevated blood/urine succinylacetone 6, 1

• Galactosemia: Start lactose-free feeding immediately until excluded, as this is life-saving treatment 2, 5

• Alpha-1 antitrypsin deficiency: Neonatal cholestasis with hepatomegaly; perform phenotyping by isoelectric focusing in all infants with conjugated hyperbilirubinemia 3, 6

Neonatal Hemochromatosis (9% of cases)

• Leading cause of acute liver failure requiring transplantation in neonates
• Presents within first days of life with severe hepatic injury and iron overload
• Characterized by low or near-normal transaminases despite profound synthetic dysfunction 6, 1

Infection (17% of cases)

• Start acyclovir immediately until herpes simplex virus infection is excluded, as this is life-saving treatment 2
• Viral infections typically produce high transaminases and coagulopathy 1

Critical Management Steps

Immediate actions upon recognition:

1. Urgent referral to pediatric liver transplant center is mandatory for any neonate with acute liver failure or acute decompensation 6, 4

2. Initiate empiric acyclovir until HSV excluded 2

3. Switch to lactose-free feeding until galactosemia excluded 2, 5

4. Correct coagulopathy with fresh frozen plasma and vitamin K 1

5. Monitor for hypoglycemia every 2-4 hours, as encephalopathy in neonates usually reflects specific metabolic derangements rather than hepatic encephalopathy 5

Common Pitfalls to Avoid

• Do not rely on transaminase levels alone: Normal or mildly elevated transaminases do not exclude severe liver failure in neonates 1, 5

• Do not wait for jaundice: One-quarter of infants with acute liver failure lack visible jaundice at presentation 1

• Do not delay transplant referral: Mortality remains 40-50% despite intensive care, and early contact with transplant centers improves outcomes 1, 4

• Do not overlook conjugated bilirubin: In neonates with any jaundice, always fractionate bilirubin, as conjugated hyperbilirubinemia indicates parenchymal liver disease requiring urgent evaluation 3, 7