Establichment of CHLA's ChilDREN Clinical Center

描述(由申请人提供)： 婴儿和儿童胆汁淤积性肝病是罕见的，但具有破坏性的疾病。胆道闭锁(BA)和特发性新生儿肝炎(由胆道闭锁研究联盟研究)，以及Alagille综合征(AGS)、α-1抗胰酶缺乏、进行性肝内胆汁淤积、胆汁酸合成缺陷、线粒体肝病和囊性纤维性肝病(由胆汁淤积性肝病研究联盟研究)共同代表了儿童胆汁淤积性肝病的绝大多数原因。儿童肝病研究和教育网络(儿童)将作为合并后的实体，通过该实体，以前由美国国立卫生研究院资助的两个网络的研究工作将继续协调侧重于这些重大儿科肝病的调查工作。目前，洛杉矶儿童医院(CHLA)服务的南加州庞大且种族多样化的人口中的患者不被招募到这两个网络中。为了在CHLA建立一个新的儿童CC，我们提出了以下具体目标：1)运作CHLA儿童CC组织基础设施，筛选和招募儿童中符合条件的受试者，以收集临床数据和样本，用于测试、处理、存储和运送到财团储存库；参与胆道闭锁类固醇的安全性和有效性临床试验。2)建立扩展到该地区的机制，包括洛杉矶、奥兰治县、 文图拉、圣路易斯奥比斯波、克恩、河滨和圣贝纳迪诺，包括一条免费转诊电话和 将IRB批准的文件分发给潜在的医疗保健提供者转介来源网络，以解决所有婴儿胆汁淤积性肝病病例；并开发教育工具以提高对儿科肝病的认识，包括在边远医院的教育查房以及大量发送教育传单。3)与其他CC调查人员合作，通过持续的电话会议和会议，并为辅助研究提供科学投入和建议，参与儿童的组织和操作；辅助项目提案：表征参与肝脏祖细胞命运的信号通路的变化，有助于BA和AGS的发病。 相关性：婴儿和儿童胆汁淤积性肝病是罕见的。单独一家医院不能积累足够的经验来做出有意义的科学贡献，这些贡献是这些疾病管理算法的基础。儿童将促进更多患有这些罕见疾病的患者的积累，以促进对这些毁灭性疾病的了解和治疗。

DESCRIPTION (provided by applicant): Infant and pediatric cholestatic liver diseases are rare yet devastating conditions. Biliary Atresia (BA) and idiopathic neonatal hepatitis, studied under the Biliary Atresia Research Consortium, along with Alagille syndrome (AGS), alpha-1-antitrypsin deficiency, progressive intrahepatic cholestasis, bile acid synthesis defects, mitochondrial hepatopathies, and cystic fibrosis liver disease, studied under the Cholestatic Liver Consortium collectively represent the vast majority of causes of cholestatic liver diseases in children. The Childhood Liver Disease Research and Education Network (ChiLDREN) will serve as the merged entity by which the research efforts from both previously NIH-funded networks will continue to coordinate investigative efforts focused on these significant pediatric liver diseases. Currently, patients from the large and ethnically diverse population of Southern California served by Childrens Hospital Los Angeles (CHLA) are not recruited into either network. In order to establish a new ChiLDREN CC at CHLA, we propose the following specific aims: 1) Operationalize the CHLA ChiLDREN CC organizational infrastructure, screen and enroll eligible subjects in ChiLDREN for collection of clinical data and specimens for testing, processing, storage, and shipping to the consortium repositories; participate in the biliary atresia steroid safety and efficacy clinical trial.2) Establish mechanisms for outreach into the region including the counties of Los Angeles, Orange, Ventura, San Luis Obispo, Kern, Riverside, and San Bernardino including a toll-free referral line and distribute IRB-approved documents to network of potential healthcare provider referral sources for all infant cholestatic liver disease cases; and develop educational tools to increase awareness of pediatric liver diseases including education rounds at outlying hospitals as well as mass mailings of educational flyers.3) Collaborate with the other CC investigators and participate in the organization and operation of ChiLDREN through ongoing conference calls and meetings and provision of scientific input and proposals for ancillary studies; ancillary project proposal: Characterize alterations in signaling pathways involved in hepatic progenitor cell fate contribute to the pathogenesis of BA and AGS. Relevance: Infant and pediatric cholestatic liver diseases are rare. Alone, individual hospitals cannot accumulate sufficient experience to make meaningful scientific contributions which are the basis for the management algorithms of these diseases. ChiLDREN will facilitate the accrual of larger cohorts of patients with these rare diseases to advance knowledge and treatment of these devastating diseases.