A PROSPECTIVE DATABASE OF INFANTS WITH CHOLESTASIS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。本研究的主要目的是建立(1)一个包含临床信息的数据库和(2)一个新生儿肝脏疾病（如胆道闭锁和新生儿肝炎）患儿的血液和组织样本库，以促进对这些重要的儿童肝脏问题的研究。使用该数据库和储存库的例子是研究胆道闭锁和新生儿肝炎的发病机制和自然史，或通过病毒、基因组和蛋白质组学技术评估组织标本和血浆中细胞基因和蛋白质的表达模式。研究人群将包括在胆道闭锁研究联盟（BARC）临床站点诊断时小于或等于180天的胆汁淤积症婴儿，包括男性和女性。为了研究自然病史，受试者将被随访至10岁，肝移植，或对于没有胆道闭锁的儿童，直到完全停止所有治疗。多中心的研究人员网络将探讨发生在生命最初几个月的最具破坏性的儿童疾病之一的病因、发病机制、自然史、诊断和新治疗方法，胆道闭锁和相关疾病，如特发性新生儿肝炎。尽管这些疾病并不常见，但对儿童、兄弟姐妹及其家庭的影响以及对肝移植的频繁需求，要求科学界比过去更加重视。此外，从这些调查中获得的知识极有可能影响成人胆汁淤积性肝病的诊断和治疗，并提高我们对调节胆汁流动、细胞保护以及肝脏和胆道发育的基本过程的理解。从患有各种新生儿胆汁淤积症的儿童中建立血清和组织标本库将是当前和未来研究婴儿肝胆损伤的病因和发病机制的宝贵工具。

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. The primary objectives of this research study are to establish (1) a database containing clinical information and (2) a repository of blood and tissue samples from children with neonatal liver disease such as biliary atresia and neonatal hepatitis to facilitate research in these important liver problems in children. Examples of the use of this database and repository are to study the pathogenesis and natural history of biliary atresia and neonatal hepatitis or to evaluate patterns of cellular gene and protein expression in tissue specimens and plasma by viral, genomic and proteomic techniques. The study population will consist of infants, both male and female, with cholestasis who are less than or equal to 180 days old at the time of diagnosis at a Biliary Atresia Research Consortium (BARC) clinical site. In order to study the natural history, subjects will be followed until 10 years of age, liver transplantation or, for children without biliary atresia, until complete recovery off of all therapy. The multi-center network of investigators will address issues of etiology, pathogenesis, natural history, diagnosis, and novel treatments for one of the most devastating pediatric illnesses that occur in the first few months of life, biliary atresia, and related disorders such as idiopathis neonatal hepatitis. Although these disorders are not common, the effects on children, siblings, and their families and the frequent need for Liver transplantation, mandate a greater degree of attention by the scientific community than in the past. Moreover, knowledge gained from these investiagtions has a high likelihood of affecting diagnosis and treatment of adults with cholestatic liver disease and improving our understanding of fundamental processes regulating bile flow, cytoprotection, and liver and biliary development. The development of a serum and tissue bank of specimens from children with various neonatal cholestatic disorders will be invaluable tool for current and future investigations into the etiology and pathogenesis of hepatobiliary injury to the infant.