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

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心机构，不一定为研究者机构。胆道闭锁是婴儿胆汁淤积（胆汁流动阻塞）的最常见原因，也是小儿肝移植的最常见适应症。这种疾病是由破坏性的炎症过程引起的，影响肝内和肝外胆管，导致胆道纤维化和闭塞。虽然对胆道闭锁的病因或发病机制知之甚少，但流行病学和病毒学研究指出了一种复杂的性状障碍，其中环境因素触发炎症过程，该过程在出生后发育的特定阶段识别并异常靶向胆道系统。 无论疾病发展的起始（环境）和修饰（遗传）因素如何，胆道上皮的炎症和纤维化破坏在所有临床形式的胆道闭锁中是常见的。门肠吻合术（加塞手术，利用肠制造人工胆管）是目前唯一用于改善胆道闭锁婴儿胆汁引流的手术。虽然及时诊断和手术干预可能会诱导胆汁流动，但超过50%的患者在2岁时进展为终末期肝病。在这种情况下，皮质类固醇治疗可能减少这种炎症成分，可能会导致改善胆汁流量和更好的结果后，门肠吻合。 我们提出了一个多中心、随机、双盲、安慰剂对照试验，以前瞻性地确定皮质类固醇对胆道闭锁婴儿预后的疗效。该试验将由NIDDK资助的9个临床中心组成的网络进行，包括胆道闭锁临床研究联盟（BARC），其目标是研究胆道闭锁婴儿的病因，发病机制，诊断和治疗。 假设：在这项临床试验中，我们建议客观地确定皮质类固醇治疗是否能改善胆道闭锁婴儿的胆汁流量。

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.