Clinical Center for Cholestatic Liver Disease in Children

描述(由申请人提供)： 我们建议将我们的会员身份从胆道闭锁研究联盟(BARC)和胆汁淤积性肝脏联盟(CLIC)转变为新的儿童肝病研究和教育网络(儿童)。我们的建议代表了我们中心长期承诺的合理延伸，即通过创新的以患者为基础的研究来改善慢性肝病儿童的护理。自BARC和CLIC分别于2002年和2004年成立以来，我们一直是这两家公司的创始成员。我们与财团调查人员合作，建立基础设施，进行以患者为基础的胆道闭锁和胆汁淤积综合征研究。我们的主要贡献包括两项回溯性研究的数据提交和分析、临床试验开发的领导、三项前瞻性研究和一项干预性研究中受试者的高入选和保留、胆道闭锁新分子表型的辅助研究的完成、胆汁酸合成缺陷的试点项目的完成、以及参与与项目审查、手稿写作和核心资源开发相关的工作组和委员会。我们期待着通过三个目标为儿童的行动作出重大贡献。在目标1中，我们将结合BARC和CLIC的专业知识和资源来组建儿童。为此，将把正在进行的研究方案的运作过渡到指导委员会和数据协调中心制定的工作结构，制定新的研究方案，并继续将受试者纳入核准的研究。在目标2中，我们将促进专业培训，开发两项核心服务(胆汁酸生物化学核心和组织病理学核心)，并通过与多伦多患病儿童医院肝病和肝移植项目的研究人员合作，显著扩大研究对象的获取途径。在目标3中，我们将使用最先进的分子和细胞系统来研究肝脏疾病的发病机制，并使用儿童方案收集的数据和组织来确定胆道闭锁和胆汁淤积综合征儿童的新治疗靶点。 相关性：我们建议成为儿童肝病研究和教育网络的成员，并为发展慢性肝病儿童的临床研究基础设施做出贡献。这一基础设施将促进以患者为基础的创新研究，解决胆道闭锁和遗传性胆汁淤积综合征儿童的病因、发病机制和临床结果。

DESCRIPTION (provided by applicant): We propose to transition our membership status from the Biliary Atresia Research Consortium (BARC) and the Cholestatic Liver Consortium (CLiC) to the new Childhood Liver Disease Research and Education Network (ChiLDREN). Our proposal represents a logical extension of the long-standing commitment of our Center to improve the care of children with chronic liver disease through innovative patient-based research. We have been a charter member of BARC and CLiC since their creation in 2002 and 2004, respectively. We worked collaboratively with consortium investigators to build the infrastructure to conduct patient-based studies on biliary atresia and cholestatic syndromes. Our key contributions included data submission and analysis of two retrospective studies, leadership in the development of a clinical trial, high enrollment and retention of subjects into three prospective studies and one interventional study, completion of an ancillary study of novel molecular phenotypes of biliary atresia, completion of a pilot project on defects in bile acid synthesis, and participation in working groups and committees related to project reviews, writing of manuscripts, and development of core resources. We look forward to significantly contributing to the operation of ChiLDREN through three aims. In Aim 1, we will combine the expertise and resources of BARC and CLiC to form ChiLDREN. This will be done by transitioning the operation of ongoing study protocols to the working structure developed by the Steering Committee and the Data Coordinating Center, develop new study protocols, and continue to enroll subjects into approved studies. In Aim 2, we will promote specialty training, develop two core services (Bile Acid Biochemistry Core and Histopathology Core), and significantly expand access to study subjects by collaborating with investigators in the Hepatology and Liver Transplant Program at the Hospital for Sick Children, Toronto. And in Aim 3, we will use state-of-the-art molecular and cellular systems to study pathogenesis of liver disease and identify novel therapeutic targets for children with biliary atresia and cholestatic syndromes using data and tissue collected by ChiLDREN protocols. Relevance: We propose to become a member of the Childhood Liver Disease Research and Education Network and to contribute to the development of the infrastructure for clinical research in children with chronic liver disease. This infrastructure will facilitate innovative patient-based studies addressing etiology, pathogenesis, and clinical outcome of children with biliary atresia and inherited cholestatic syndromes.