Biliary atresia: Pathogenesis and treatment

Biliary atresia is a disorder of infants in which there is obliteration or discontinuity of the extrahepatic biliary system, resulting in obstruction of bile flow. Untreated the resulting cholestasis leads to progressive conj ugated hyperbilirubinemia, cirrhosis, and hepatic failure. Biliary atresia has an incidence of approximately one in 10,000 live births worldwide. Evid ence to date supports a number of pathogenic mechanisms for the development of biliary atresia. An infectious cause, such as by a virus, would seem mo st pausible in many cases. The clinical observation that biliary atresia is rarely encountered in premature infants would support an agent acting late in gestation. However no infectious or toxic agent has been conclusively i mplicated in biliary atresia. Genetic mechanisms likely play important role s, even regarding susceptibility to other specific causes, but no gene whos e altered function would result in obstruction or atresia of the biliary tr ee has been identified. The variety of clinical presentations support the n otion that the proposed mechanisms are not mutually exclusive but may play roles individually or in combination in cer-tain patients, Biliary atresia, when untreated, is fatal within 2 years, with a median sur vival of 8 months. The natural history of biliary atresia has been favorabl y altered by the Kasai portoenterostomy Approximately 25 to 35% of patients who undergo a Kasai portoenterostomy will survive more than 10 years witho ut liver transplantation. One third of the patients drain bile but develop complications of cirrhosis and require liver transplantation before age 10. For the remaining one third of patients, bile flow is inadequate following portoenterostomy and the children develop progressive fibrosis and cirrhos is. The portoenterostomy should be clone before there is irreversible scler osis of the intrahepatic bile ducts. Consequently, a prompt evaluation is i ndicated for arty infant older than 14 days with jaundice to determine if c onjugated hyperbilirubinemia is present. If infectious, metabolic, endocrin e disorders are unlikely and if the child has findings consistent with bili ary atresia, then exploratory laparotomy and intraoperative cholangiogram s hould be done expeditiously by a surgeon who has experience doing the Kasai portoenteostomy. Biliary atresia represents the most common indication for pediatric liver transplantation, representing more than 50% of cases in mo st series. Transplantation is indicated when symptoms of end stage liver di sease occur, including recurrent cholangitis, progressive jaundice, portal hypertension complications, ascites, decreased synthetic function, and grow th/nutritional failure.