Biliary Atresia

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Biliary atresia is a neonatal obstructive cholangiopathy characterized by a fibrosclerosing obliteration of the extrahepatic bile duct that uniquely presents in the first months of life (1). The condition occurs in approximately 1 in 8,000 to 1 in 15,000 live births and accounts for 30% of all cases of cholestasis in young infants. Biliary atresia is the most frequent cause of chronic end-stage liver disease in children and the leading indication for liver transplantation in the pediatric population, accounting for 40% to 50% of all pediatric liver transplants. Two forms of this disease have been recognized recently. In the embryonic type, which occurs in 15% to 30% of cases, the cholestatic manifestations of biliary atresia present at birth in association with other extrahepatic anomalies, including polysplenia, portal vein anomalies, malrotation, abdominal situs inversus, and congenital heart disease (2). With the classic perinatal type of biliary atresia, accounting for 70% to 85% of cases, the clinical features of jaundice and acholic stools manifest within the first 2 weeks of life with no other associated abnormalities. With both subtypes, complete obstruction of bile flow develops as a result of a sclerosing fibro-obliteration of the extrahepatic bile duct.No curative therapy for biliary atresia exists. The initial treatment is surgical, involving resection of the obliterated extrahepatic bile duct and creation of a hepatoportoenterostomy (Kasai procedure). The Kasai procedure should be performed before 2 months of age to successfully reestablish bile flow. For many infants, delayed recognition of the disease and delayed referral for specialty care remain major obstacles to optimal timing of this initial surgical intervention. Yet even with early surgery, most patients (70–80%) eventually develop end-stage biliary cirrhosis and require liver transplantation (3). In the United States, the annual cost for this disease is approximately $65 million. Despite current treatment efforts, biliary atresia remains the most serious and costly liver disease that affects infants.The cause and pathogenesis of either embryonic or perinatal biliary atresia are not known. Genetic, viral, and host immune factors are putative etiopathogenic mechanisms of this disorder. The lack of suitable animal models hampers this research. Furthermore, the paucity of cases at any one center has limited the availability of sufficient human tissue samples to study pathogenic mechanisms and has limited the development of amply sized clinical trials to test new treatment strategies. Research efforts should be directed toward defining disease cause and pathogenesis, developing methods of early detection, and creating more effective therapeutic interventions. More formalized educational programs in the medical and lay communities are necessary to allow earlier recognition of this condition.AREAS OF EMPHASISGenetic FactorsAlthough several reports describe families in which male and female siblings have the disease, identical twins discordant for the condition have been described frequently. Generally, biliary atresia is not considered to be an inherited disease. However, with the less common embryonic-type biliary atresia, which is associated with other congenital malformations, genetic mutations that result in defective morphogenesis may be important to disease pathogenesis. Anomalous development of bile ducts with progressive cholestasis, situs inversus, and cystic kidneys has been described in the transgenic inv mouse, raising the possibility that alterations in the inversin gene may be one genetic mechanism for some cases of embryonic biliary atresia (4). With perinatal biliary atresia, a significant increase in the HLA B12 antigen and haplotypes A9-B5 and A28-B35 has been reported in one study but not confirmed in another (4–6). Thus genetic factors may play a role in the susceptibility to develop biliary atresia, and this area must be explored further.

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