Continuation of the Childhood Liver Disease Research Network Seattle Clinical Cen

描述(申请人提供)：胆道闭锁和其他儿童胆汁淤积性肝病是儿童慢性肝病的重要原因，也是儿科肝脏移植的主要原因。进行诉讼的财团的初始资金期限 导致儿童肝病研究网络(儿童)导致了前所未有的良好表型的受试者和储存的数据和生物标本的收集。尽管需要不断招募患有这些罕见疾病的受试者，以充分实现许多单独的研究目标，但现在收集的受试者、数据和生物标本足以支持对这些疾病的发病机制进行有意义的研究，并为新疗法的研究提供信息。下一个资助期将继续并扩大目前正在进行的自然历史、遗传学和治疗方面的研究，继续完成正在进行的研究。此外，将试验新的治疗方法，以期改善为患有这些疾病的儿童提供的护理。利用主题数据、生物标本和参与研究的受试者及其家庭增进对这些疾病的了解和治疗受影响的儿童，也将是即将到来的供资期间的优先事项。西雅图临床中心拥有经验，专业知识， 以及经过证明的继续参与儿童试验的记录，并随着时间的推移有预期的患者支持新的财团试验。Murray博士和她的临床中心团队还提出了一项关于Alagille综合征受试者的出血风险和血小板功能的研究，将与患有α-1抗胰蛋白酶缺乏和进行性家族性肝内胆汁淤积症的受试者进行比较，这将填补我们对这种疾病的了解空白，并对患有Alagille综合征的儿童产生重大影响。这项研究将使用儿科出血问卷来评估这些儿童的出血风险，然后使用血小板功能分析仪-100和血栓弹性图分析他们的血小板功能。对这些儿童受试者的分析结果将与收集的有关这些受试者的联盟数据一起进行评估，以验证患有Alagille综合征的儿童具有他们的综合征特有的出血风险增加，这在一定程度上是由于血小板功能障碍。

DESCRIPTION (provided by applicant): Biliary atresia and the other childhood cholestatic liver diseases are significant causes of chronic liver disease in children, and the leading causes for liver transplantation in pediatrics. The initial funding periods for the proceeding consortiums leading to Childhood Liver Disease Research Network (ChiLDReN) have resulted in unprecedented collections of well phenotyped subjects and banked data and biological specimens. Although ongoing recruitment of subjects with these rare conditions is needed to allow full attainment of many of the individual study Aims, the collection of subjects, data, and biospecimens is now sufficient to support meaningful investigation into the pathogenesis of these diseases and inform the investigation of novel therapies. This next funding period will continue and expand the currently ongoing research of natural history, genetics, and treatment, by continuing to completion the ongoing studies. Furthermore, new therapies will be trialed in the hopes of improving the care that can be provided to children afflicted with these diseases. Usage of the subject data, biospecimens, and engaged subject populations and their families for advancement of knowledge of these diseases and treatment of affected children will also be a priority for this coming funding period. The Seattle Clinical Center has the experience, expertise, and proven track record to continue participation in ChiLDReN, and has the expected patients over time to support the new consortium trials. Dr. Murray and her Clinical Center team has also proposed a study of bleeding risk and platelet function in Alagille syndrome subjects in comparison to subjects with alpha-1-antitrypsin deficiency and progressive familial intrahepatic cholestasis, that will fill a gap in our knowledge about this condition and significantly impact children with Alagille. This study will use a Pediatric Bleeding Questionnaire to assess bleeding risk in these children, and then analyze their platelet function utilizing the Platelet Functional Analyzer-100 and thromboelastography. The results from analysis of these ChiLDReN subjects will be evaluated in conjunction with collected consortium data on these subjects to verify that children with Alagille syndrome have an increased bleeding risk unique to their syndrome and that this is in part due to platelet dysfunction.