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

描述(由申请人提供)：作为临床中心，加州大学旧金山分校将继续招募受试者参加新的优先顺序和批准的研究，以及目前正在进行的儿童研究，并将按照各自研究方案的描述进行这些临床试验和纵向后续研究的程序，没有任何偏差。加州大学旧金山分校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一起参与儿童活动的各个方面。我们计划继续执行《儿童议定书》，对我们机构中央机构审查委员会的概念持开放态度，并同意接受儿童及其指导委员会的政策和程序的管理。我们理解，并不是所有的临床中心都会参与所有批准的儿童方案。加州大学旧金山分校的临床中心是胆道闭锁研究联盟(BARC)的十个原址之一，该联盟继续、扩大和合并CLIC，形成了孩子。新生儿肝炎是指一组不同的疾病，导致不到3个月大的婴儿在受到各种侮辱时肝脏出现类似的形态变化。术语新生儿肝炎有时被用来包括婴儿时期胆汁淤积的所有原因，但不包括肝外胆道梗阻。虽然在许多病例中无法找到病因，但已经确定了特定的感染和代谢原因，可能是新生儿肝炎。新生儿肝炎是由一种已知的病因引起的，可能可以接受治疗，因此需要与特发性新生儿肝炎(INH)进行鉴别，特发性新生儿肝炎的病因不明，可能有多种。在加州大学旧金山分校，我们特别计划利用新的遗传诊断工具，并将它们应用于儿童资料库中可用的丰富样本，以阐明进一步的遗传疾病和有助于诊断INH的因素。应用最先进的基因技术和方法对这些患者的DNA样本进行研究，将使我们能够探索异型肝炎的遗传病因和相关诊断，其广度和深度比以前所做的甚至被认为可能的要大得多。我们确定的与异烟肼相关的变异也将是成人肝病评估的有力候选者，例如药物诱导的胆汁淤积。此外，我们与科罗拉多大学的Ron Sokol博士和英国伦敦国王学院医院的Richard Thompson博士合作，建议进一步开发进行性家族性肝内胆汁淤积症(PFIC)基因分型计划，用于儿童LOGIC研究中PFIC和良性复发性肝内胆汁淤积症(BRIC)患者的诊断筛查。我们建议利用当前最先进的技术，转向更具成本效益和更全面的实验方法。

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.