Clinical Center: Childhood Liver Disease Research and Education Network (ChiLDREN

描述（由申请人提供）： 肝病是婴儿和儿童发病率和死亡率的主要原因。构成“儿科肝病”的疾病个别罕见，这阻碍了对其病因/病理生理学的研究。由于这一基本缺陷，在理解有效的治疗策略是缺乏对他们中的大多数。这反过来又导致许多儿童与他们进展到终末期肝病需要原位肝移植。儿科肝移植约占所有肝移植的10%，其中大多数的适应症都属于儿童肝病研究和教育网络（ChiLDREN）研究的疾病，其主要目标是“将[胆道闭锁研究联盟] BARC和[胆汁淤积性肝脏联盟] CLiC临床中心的专业知识和资源联合收割机结合起来.研究儿科肝病”。这一目标的一个基本要素是参与者的综合专业知识，这有助于指导对所包括的个别疾病的研究。本申请的一个主要目的是作为基因决定的胆汁淤积（特别是进行性家族性肝内胆汁淤积）和一般婴儿胆汁淤积性肝病临床方面的专家参加ChiLDREN。ChiLDREN主要目标的另一个要素是临床中心贡献的资源，最重要的是肝病受试者。我们的中心一直是BARC和CLiC受试者的主要贡献者，并希望在ChiLDREN中继续如此。通过参与这些方式，我们希望为ChiLDREN的业绩做出实质性贡献，以实现其成功消除儿科肝病作为婴儿和儿童发病率和死亡率的主要原因的目标。我们中心的具体目标包括：a）作为ChiLDREN的临床中心全面参与;和B）通过设计和实施由ChiLDREN成员进行的研究，为理解进行性家族性肝内胆汁淤积症的病理生理学做出贡献。 相关性：慢性儿科肝病虽然罕见，但却是一种具有高度公共卫生影响的破坏性疾病。患有胆道闭锁或ChiLDREN研究的五种遗传性胆汁淤积性肝病中的任何一种的儿童占美国进行的儿科肝移植的大多数。

DESCRIPTION (provided by applicant): Liver disease is a major cause of infant and childhood morbidity and mortality. The diseases comprising "pediatric liver diseases" are individually rare, which has hindered the study of their causes/ pathophysiologies. As a result of this basic defect in understanding effective therapeutic strategies are lacking for most of them. This in turn results in many children with them progressing to end-stage liver disease necessitating orthotopic liver transplantation. Pediatric liver transplants comprise approximately 10% of all liver transplants performed, and the indications for most of them lie among the diseases to be studied in the Childhood Liver Disease Research and Education Network (ChiLDREN), the major objective of which is to "combine the expertise and resources of the [Biliary Atresia Research Consortium] BARC and [Cholestatic Liver Consortium] CLiC clinical centers ... to study pediatric liver diseases". An essential element of this objective is the combined expertise of the participants, which serves to guide the study of the individual diseases included. A major objective of this application is to participate in ChiLDREN as an expert in genetically determined cholestasis (in particular progressive familial intrahepatic cholestasis) and in clinical aspects of infantile cholestatic liver disease in general. The other element of the major objective of ChiLDREN is the resources to be contributed by the clinical centers, the most important being the subjects with liver disease. Our center has been a leading contributor of subjects to both BARC and CLiC and expects to continue as such in ChiLDREN. By participating in these ways we expect to contribute substantially to the performance of ChiLDREN in achieving its goal of successfully eliminating pediatric liver disease as a major cause of infant and childhood morbidity and mortality. The specific aims at our center include: a) to participate fully as a clinical center in ChiLDREN; and b) to contribute to the understanding of the pathophysiology of progressive familial intrahepatic cholestasis by designing and implementing studies to be carried out by the membership of ChiLDREN. Relevance: Chronic pediatric liver disease, although rare, is a devastating condition that has high public health impact. Children with biliary atresia or any of the five genetic cholestatic liver diseases studied by ChiLDREN account for the majority of pediatric liver transplantations performed in the United States.