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

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 胆道闭锁是婴儿胆汁淤积最常见的原因，也是小儿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。基于这些数据，可以初步提出以下统一的发病机理模型： 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。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。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量。这项试验的意义在于，它将确定皮质类固醇是否是一种有效的药物治疗，以改善胆汁引流和长期结果，以及它的使用是否减少了胆道闭锁婴儿肝移植的需要。 该试验将由NIH支持的胆道闭锁研究联盟（BARC）进行。BARC的基础设施可以前瞻性地随访足够多的患者，并收集临床研究所需的样本，这些研究涉及胆道闭锁儿童的病因、发病机制、诊断和治疗。 我们的总体假设是，门肠吻合术后皮质类固醇治疗将改善胆道闭锁婴儿的胆汁引流和长期预后。该假设将通过以下假设进行检验：

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 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. Our overall hypothesis is that therapy with corticosteroids following portoenterostomy will improve bile drainage and long-term outcome in infants with biliary atresia. This hypothesis will be tested through the following hypotheses: