Evaluation and Management of Acute and Chronic Liver Disease in Children
Age-specific differential
Neonatal liver disease is dominated by cholestasis, infection, metabolic disease, and biliary atresia; older children by autoimmune hepatitis, Wilson disease, drug injury, viral hepatitis, and metabolic or genetic disorders. Always confirm conjugated hyperbilirubinemia: a conjugated bilirubin above 1 mg/dL or more than 20% of total is pathologic and mandates urgent evaluation. Physiologic jaundice is unconjugated, appears after 24 hours, peaks by days 3 to 5, and resolves. Cholestasis presents with pale stools, dark urine, hepatomegaly, or bleeding.
Severity and synthetic function
Transaminases indicate hepatocyte injury, not liver function. Severity is judged by synthetic function (INR, albumin, bilirubin), encephalopathy, ascites, hypoglycemia, and growth. Pediatric acute liver failure requires acute liver injury without known chronic disease plus coagulopathy: INR at least 1.5 with encephalopathy or at least 2.0 without encephalopathy, after vitamin K. Encephalopathy is often subtle in infants, so irritability, poor feeding, and altered sleep are clues. Ammonia supports but does not define hepatic encephalopathy.
Traps
Do not attribute conjugated jaundice to breast-feeding. Do not wait for ALT to normalize before checking INR. A normal ceruloplasmin does not exclude Wilson disease; use exchangeable copper, 24-hour urine copper, and genetics when suspected. Acetaminophen and herbal products are common toxins.
Worked example
A 6-week-old has total bilirubin 9 mg/dL, direct 4.2 mg/dL, pale stools, and INR 1.4. This is neonatal cholestasis, not physiologic jaundice. Obtain urgent hepatology referral, stool color chart, ultrasound, fractionated bilirubin, GGT, AFP, alpha-1 antitrypsin, sweat chloride or CF testing, thyroid studies, metabolic screen, and infectious studies. Biliary atresia must be excluded promptly because Kasai portoenterostomy outcomes are best before 60 days.
Rule of thumb: any conjugated hyperbilirubinemia in infancy is a surgical or metabolic emergency until proven otherwise.