A RANDOMIZED, DOUBLE-BLINDED, PLACEBO-CONTROLLED TRIAL OF CORTICOSTEROID THERAPY

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 摘要 胆道闭锁是导致婴儿胆汁淤积的最常见原因，也是儿童肝移植最常见的适应症。这种疾病是由破坏性的炎症过程引起的，影响肝内外胆管，导致胆管纤维化和闭塞。虽然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，这是一种复杂的特质障碍，即环境因素引发炎症过程，在出生后发育的特定阶段识别并异常靶向胆道系统。基于这些数据，可以初步提出以下统一的发病机制模型： 不管疾病发展的始动(环境)和改变(遗传)因素，胆道上皮的炎性和纤维性破坏在所有临床形式的胆道闭锁中都是常见的。在这种情况下，通过糖皮质激素治疗这种炎症成分的潜在减少可能导致胆汁流量的改善和门肠吻合术后更好的结果。因此，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动。拟议中的试验的意义在于，它将确定皮质类固醇是否是改善胆汁引流和长期预后的有效药物，以及它的使用是否减少了患有胆道闭锁的婴儿进行肝移植的需要。 这项试验将由NIH支持的胆道闭锁研究联盟(BARC)进行。BARC有基础设施，可以前瞻性地跟踪足够多的患者，并收集必要的样本，以进行针对儿童胆道闭锁的病因、发病机制、诊断和治疗的临床研究。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. ABSTRACT Biliary atresia is the most common cause of cholestasis 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. Based on these data, the following unifying pathogenesis model can be preliminarily proposed: 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. In this setting, the potential decrease of this inflammatory component by corticosteroid treatment may result in improved bile flow and better outcome after portoenterostomy. Therefore, in this clinical trial we propose to objectively determine whether corticosteroid treatment improves bile flow in infants with biliary atresia. The significance of the proposed trial is that it will determine whether corticosteroids are an effective medical treatment to improve bile drainage and long-term outcome, and whether its use reduces the need for liver transplantation in infants with biliary atresia. The trial will be performed by the NIH-supported Biliary Atresia Research Consortium (BARC). BARC has the infrastructure to prospectively follow a sufficiently large number of patients and to collect samples necessary for clinical research studies addressing etiology, pathogenesis, diagnosis, and treatment of children with biliary atresia.