Biliary atresia and other disorders of the extrahepatic bile ducts

Biliary atresia and related disorders of the biliary tract, such as choledochal cysts, must be considered in the differential diagnosis of prolonged conjugated hyperbilirubinemia in the newborn (neonatal cholestasis). Neonatal hepatobiliary diseases, including biliary atresia, choledochal cysts, and “idiopathic” neonatal hepatitis, have historically been viewed as a continuum – a gradation of manifestations of a basic underlying disease process in which giant cell transformation of hepatocytes is strongly associated with inflammation at any level of the hepatobiliary tract. These disease entities may be polar end-points of a common initial insult, as originally stated in the unifying hypothesis of Landing [1]. The end result represents the sequelae of the inflammatory process at the primary site of injury. Landing suggested that this inflammatory process may injure bile duct epithelial cells, leading to either duct obliteration (biliary atresia) or weakening of the bile duct wall with subsequent dilatation (choledochal cyst). The lesions may be dependent on the stage of fetal or early postnatal development when the injury occurs and the site within the developing hepatobiliary tree at which the injury occurs [1, 2]. The recent observation that extrahepatic bile ducts develop cystic dilatations following rotavirus infection in newborn mice genetically primed to have a prominent T helper lymphocyte type 2 response suggests that the lesions may also be dependent on the type of immune response to the viral insult [3]. A relationship between the pathogenesis of these obstructive cholangiopathies of infancy and the process of development (embryogenesis) is suggested by the association with disorders of situs determination such as the polysplenia syndrome and the observation of the so-called ductal plate malformation within the liver of a few patients with biliary atresia. The ductal plate malformation is postulated to represent either a primary developmental anomaly or disruption of a developmental sequence early in fetal life, resulting in incomplete regression of the immature bile ducts [2]. In contrast, most patients with biliary atresia have the late-onset type, which probably occurs after the anatomic formation of intra- and extrahepatic bile ducts; this represents injury (destruction) of fully formed structures [1]. The dynamic nature of the underlying process has been further suggested by an apparent postnatal evolution of patent to atretic ducts: patients initially shown to have “neonatal hepatitis” with a patent biliary system were subsequently found to have acquired biliary atresia.