Neonatal Cholestasis Prolonged conjugated hyperbilirubinemia in the neonate, termed neonatal cholestasis (as opposed to the already dis- cussed neonatal jaundice) affects approximately 1 in 2500 live births. The major conditions causing it are (1) cholan- giopathies, primarily biliary atresia (discussed later), and (2) a variety of disorders causing conjugated hyperbilirubine- mia in the neonate, collectively referred to as neonatal hepatitis. Neonatal hepatitis is not a specific entity, nor does it necessarily have an inflammatory basis. Rather it is an indication to conduct a diligent search for recognizable toxic, metabolic, and infectious liver diseases, as greater than 85% of cases have identifiable causes. Differentiation of biliary atresia from nonobstructive neonatal cholestasis is very important, since definitive treatment of biliary atresia requires surgical intervention (Kasai procedure), whereas surgery may adversely affect a child with other disorders. Fortunately, discrimination can be made on the basis of clinical data in about 90% of cases. In 10% of cases, liver biopsy may be necessary to distin- guish neonatal hepatitis from an identifiable cholangiopa- thy. Affected infants have jaundice, dark urine, light or acholic stools, and hepatomegaly. Variable degrees of hepatic synthetic dysfunction may be identified, such as hypoprothrombinemia. MORPHOLOGY The morphologic features of neonatal hepatitis (Fig. 16.26) include striking giant-cell transformation of hepatocytes, associ- ated with lobular disarray, focal liver cell apoptosis and promi- nent hepatocellular and canalicular cholestasis. In some cases, this parenchymal pattern of injury also is accompanied by ductu- lar reaction and fibrosis of portal tracts.