BILLARY ATRESIA (BA) CLINICAL RESEARCH-CORTICOSTEROID THERAPY IN INFANTS WITH BA

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Biliary atresia is the most common cause of cholestasis (bile flow blockage) in infants and the most frequent indication for pediatric liver transplantation. The disease results from a destructive inflammatory process that affects intra- and extrahepatic bile ducts, leading to fibrosis and obliteration of the biliary tract. Although little is known about the etiology or pathogenesis of biliary atresia, epidemiologic and virologic studies point to a complex trait disorder, in which environmental factors trigger an inflammatory process that recognizes and abnormally targets the biliary system during a specific phase of postnatal development. Regardless of initiating (environmental) and modifying (genetic) factors for disease development, the inflammatory and fibrosing destruction of the biliary epithelium is common to all clinical forms of biliary atresia. Portoenterostomy (Kasai procedure utilizing the intestine to make an artificial bile duct) is the only operative procedure used currently to improve bile drainage in infants with biliary atresia. Although prompt diagnosis and surgical intervention may induce bile flow, progression to end-stage liver disease occurs in over 50% of the patients by 2 years of age. In this setting, the potential decrease of this inflammatory component by corticosteroid treatment may result in improved bile flow and better outcome after portoenterostomy. We propose a multi-center randomized, double-blinded, placebo-controlled trial to prospectively determine the efficacy of corticosteroids on the outcome of infants with biliary atresia. The trial will be conducted by the NIDDK-funded network of nine clinical centers comprising the Biliary Atresia Clinical Research Consortium (BARC), whose goal is to study the etiology, pathogenesis, diagnosis, and treatment of infants with biliary atresia. Hypothesis: In this clinical trial we propose to objectively determine whether corticosteroid treatment improves bile flow in infants with biliary atresia.