1. Ian D. D’Agata, MD* 2. William F. Balistreri, MD† 1. 2. *Pediatric Gastroenterology & Liver Diseases, Valley Children’s Hospital, Madera, CA. 3. 4. †Chief, Division of Gastroenterology & Nutrition, Children’s Hospital Medical Center, Cincinnati, OH. After completing this article, readers should be able to: 1. List the age-specific causes of liver disease in neonates, infants, older children, and adolescents. 2. Explain why fractionation of serum bilirubin is necessary in infants who remain jaundiced after 2 weeks of age. 3. Characterize the syndrome of “neonatal hepatitis” and explain how it differs from viral hepatitis. 4. Characterize biliary atresia and identify findings from the history, physical examination, and laboratory evaluation that may suggest this diagnosis. 5. Describe a quick, cost-effective diagnostic approach to a neonate who presents with cholestasis. Because clinicians often do not recognize the presence of underlying liver disease, precise documentation of the disorder can be delayed, which can lead to a subsequent delay in the initiation of effective therapies. Liver transplantation is a reality for pediatric patients who have severe or end-stage liver disease, and other therapies also are now available for treating many liver diseases. The estimated incidence of neonatal liver disease is as high as 1 in 2,500 live births. Early recognition is particularly important in neonates and infants because a delay in diagnosis may have a negative effect on the prognosis. For example, it is well recognized that when biliary atresia is diagnosed after 2 months of age, the success rate of surgical repair (Kasai hepatoportoenterostomy) declines sharply. Furthermore, because liver dysfunction is progressive, early recognition allows for better nutritional support of the patient and a potentially slower decline in liver function. The result can be improved growth and fewer complications. This is of considerable importance because orthotopic liver transplantation generally is more successful in infants who weigh more than 10 kg at the time of surgery. Unfortunately, the timely recognition of severe liver disease in the pediatric patient remains a major problem. One contributing factor is that injury to the pediatric liver manifests in a …