Cholestasis is defined as reduced bile flow and is characterized by elevation of the conjugated, or direct, bilirubin fraction. This condition must be distinguished from ordinary neonatal jaundice, in which the direct bilirubin is never elevated (see Chapter 62). Neonatal jaundice that is secondary to unconjugated hyperbilirubinemia is the result of immature hepatocellular excretory function or hemolysis, which increases the production of bilirubin. When direct bilirubin is elevated, many potentially serious disorders must be considered (Fig. 130-1). Emphasis must be placed on the rapid diagnosis of treatable and potentially imminently lethal disorders, especially biliary atresia and metabolic disorders, such as galactosemia or tyrosinemia.
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The jaundice of extrahepatic biliary atresia (biliary atresia) usually is not evident immediately at birth, but develops in the first week or two of life. The reason is that extrahepatic bile ducts are usually present at birth, but are then destroyed by an idiopathic inflammatory process. Aside from jaundice, these infants do not initially appear ill. The liver injury progresses rapidly to cirrhosis; symptoms of portal hypertension with splenomegaly, ascites, muscle wasting, and poor weight gain are evident by a few months of age. If surgical drainage is not performed successfully early in the course (ideally by 2 months), progression to liver failure is inevitable.
Neonatal hepatitis is characterized by an ill-appearing infantwith an enlarged liver and jaundice. There is no specific diagnostic test. If liver biopsy is performed, the presence of hepatocytegiant cells is characteristic. Cytomegalovirus, herpes simplexvirus, and syphilis must be ruled out. Hepatobiliary scintigraphy typically shows slow hepatic uptake with eventual excretionof isotope into the intestine. These infants have a good prognosis overall, with spontaneous resolution occurring in most.
α1-Antitrypsin deficiency presents with clinical findings indistinguishable from neonatal hepatitis. Only about 10% to 20% of all infants with the genetic defect exhibit neonatal cholestasis. Of these affected infants, about 20% to 30% develop chronic liver disease, which may result in cirrhosis and liver failure. Life-threatening α1-antitrypsin deficiency occurs in only 3% to 5% of affected pediatric patients. α1-Antitrypsin deficiency is the leading metabolic disorder requiring liver transplantation.
Alagille syndrome is characterized by chronic cholestasis with the unique liver biopsy finding of paucity of bile ducts in the portal triads. Associated abnormalities in some (syndromic) types include peripheral pulmonic stenosis or other cardiac anomalies; hypertelorism; unusual facies with deep-set eyes, prominent forehead, and a pointed chin; butterfly vertebrae; and a defect of the ocular limbus (posterior embryotoxon). Cholestasis is variable but is usually lifelong and associated with hypercholesterolemia and severe pruritus. Progression to end-stage liver disease is uncommon. Liver transplantation sometimes is performed electively to relieve severe and uncontrollable pruritus.
The laboratory approach to diagnosis of a neonate with cholestatic jaundice is presented in Table 130-1. Noninvasive studies may aid a rapid diagnosis. Early imaging studies are performed to evaluate for biliary obstruction and other anatomic lesions that may be surgically treatable. When necessary to rule out biliary atresia or to obtain prognostic information, liver biopsy is a final option (Fig. 130-2).
Treatment of extrahepatic biliary atresia is the surgical Kasai procedure, in which the fibrotic extrahepatic bile duct remnant