Childhood Liver Disease Research and Education Network (ChiLDREN) - UCSF (CC)

描述（由申请人提供）：作为一个临床中心，UCSF将继续招募受试者进入新优先和批准的研究，以及目前正在进行的ChiLDREN研究，并将进行这些临床试验和纵向随访研究的程序，如各自的研究方案所述，没有任何偏离。UCSF临床中心将以合作和互动的方式与其他临床中心，数据协调中心和NIDDK参与ChiLDREN活动的各个方面。我们计划继续执行ChiLDREN的协议，对我们机构的集中机构审查委员会的概念持开放态度，并同意接受ChiLDREN及其指导委员会的政策和程序的管理。我们理解，并非所有临床中心都必须参与所有已批准的ChiLDREN方案。UCSF临床中心是胆道闭锁研究联盟（BARC）的十个原始站点之一，该联盟继续，扩大并与CLiC合并，形成ChiLDREN。新生儿肝炎是指一组异质性疾病，其导致小于3个月龄的婴儿对各种损伤作出反应时肝脏发生相似的形态学变化。术语新生儿肝炎有时被用来包括婴儿期胆汁淤积的所有原因，其中肝外胆道梗阻被排除在外。虽然在许多情况下无法找到病原学，但已确定可能表现为新生儿肝炎的特定感染和代谢原因。由已知病原体引起的新生儿肝炎可能适合治疗，需要与特发性新生儿肝炎（INH）区分开来，其中病原体未知且可能是多种。在UCSF，我们特别计划利用新的遗传诊断工具，并将其应用于ChiLDREN库中丰富的样本，以进一步阐明有助于INH诊断的遗传疾病和因素。应用最先进的遗传技术和方法来研究来自这些患者的DNA样本将使我们能够探索INH和相关诊断的遗传病因学，其广度和深度比以前所做的要大得多，甚至被认为是可能的。我们鉴定为与INH相关的变体也将是用于评估成人肝脏疾病（例如药物诱导的胆汁淤积）的强有力的候选者。此外，与科罗拉多大学的罗恩索科尔博士和英国伦敦国王学院医院的Richard Thompson博士合作，我们建议进一步开发一种进行性家族性肝内胆汁淤积症（PFIC）基因分型程序，用于ChiLDREN LOGIC研究中PFIC和良性复发性肝内胆汁淤积症（BRIC）受试者的诊断筛查。我们建议转向更具成本效益和综合性的实验方法，利用当前最先进的技术。

DESCRIPTION (provided by applicant): As a Clinical Center, UCSF will continue to recruit subjects into the newly prioritized and approved studies, as well as the currently ongoing ChiLDREN studies, and will conduct the procedures for these clinical trials and longitudinal follow-up studies, as described in their respective study protocols, without any deviations. The UCSF Clinical Center will participate in a cooperative and interactive manner with other Clinical Centers, with the Data Coordinating Center, and with the NIDDK in all aspects of the ChiLDREN activities. We plan to continue to carry out the protocols of the ChiLDREN, be open to the concept of a centralized Institutional Review Board at our institution, and agree to be governed by the policies and procedures of the ChiLDREN and its steering committee. We understand that not all Clinical Centers will necessarily participate in all of the approved ChiLDREN protocols. The UCSF Clinical Center is one of the ten original sites in the Biliary Atresia Research Consortium (BARC) which continued, expanded and merged with CLiC to form ChiLDREN. Neonatal hepatitis refers to a heterogeneous group of disorders that result in similar morphologic changes in the livers of infants less than 3 months of age in response to various insults. The term neonatal hepatitis has been used at times to include all causes of cholestasis in infancy in which extra-hepatic biliary obstruction is excluded. Although in many of the cases an etiology cannot be found, specific infectious and metabolic causes have been identified that may present as neonatal hepatitis. Hepatitis in a neonate caused by a known etiologic agent that may be amenable to therapy needs to be differentiated from idiopathic neonatal hepatitis (INH), in which etiologic agents are unknown and probably multiple. At UCSF, we specifically plan to utilize new genetic diagnostic tools and apply them to the rich samples available in the ChiLDREN repository, to elucidate further genetic disorders and factors that contribute to the diagnosis of INH. Application of state- of-the-art genetic technologies and approaches to study of DNA samples from these patients will allow us to explore the genetic etiologies underlying INH and related diagnoses to a much greater breadth and depth than has previously been done, or even been considered possible. Variants that we identify as being associated with INH will also be strong candidates for evaluation in adult liver disorders, such as drug- induced cholestasis. Further, in collaboration with Dr. Ron Sokol at the University of Colorado and Dr. Richard Thompson at King's College Hospital in London, UK we propose to further develop a Progressive Familial Intrahepatic Cholestasis (PFIC) Genotyping Program for diagnostic screening for PFIC and Benign Recurrent Intrahepatic Cholestasis (BRIC) subjects in the ChiLDREN LOGIC study. We propose to shift to more cost-effective and comprehensive experimental approaches making use of current state-of-the art technologies.