Continuation of ChiLDReN, the Childhood Liver Disease Research Network: Indiana University

ChiLDReN 的延续，儿童肝病研究网络：印第安纳大学

• 批准号: 10019515
• 负责人: Jean Pappas Molleston
• 金额: $ 47.94万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-10 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10019515
• 关键词: Alagille Syndrome; Alcoholic Liver Cirrhosis; Behavioral; Bile Acids; Biliary Atresia; Biliary cirrhosis; Biological Markers; Child; Childhood; Cholestasis; Cirrhosis; Clinical Data; Clinical Management; Clinical Trials; Collaborations; Cystic Fibrosis; Data; Databases; Defect; Development; Diagnosis; Disease; Education; Enrollment; Equipment and supply inventories; Fibrosis; Frequencies; Future; Genetic; Goals; Hepatic Encephalopathy; Impairment; Indiana; Intestines; Knowledge; Lactulose; Learning; Liver Fibrosis; Liver diseases; Magnetic Resonance Elastography; Malnutrition; Medical; Mitochondria; Monitor; Morbidity - disease rate; Multicenter Studies; Natural History; Neonatal; Outcome; Parents; Pathogenesis; Patient Recruitments; Patients; Performance; Portal Hypertension; Progressive intrahepatic cholestasis; Pruritus; Public Health; Quality of life; Rare Diseases; Reporting; Research; Risk Factors; Role; Surveys; Therapeutic Trials; Translational Research; Ultrasonography; Universities; alpha 1-Antitrypsin Deficiency; biobank; children with cystic fibrosis; chronic liver disease; elastography; executive function; follow-up; improved; insight; liver cystic fibrosis; liver transplantation; mortality; neurocognitive test; non-invasive monitor; primary sclerosing cholangitis; transport inhibitor

PROJECT SUMMARY/ABSTRACT Pediatric liver disease has significant morbidity and mortality. Biliary atresia (BA) accounts for more than half of pediatric liver transplants. Genetic causes of neonatal cholestasis include Alagille's syndrome (ALGS), alpha-1 antitrypsin deficiency (A1AT), Progressive Familial Intrahepatic Cholestasis (PFIC), bile acid synthetic defects, mitochondrial hepatopathies, and cystic fibrosis (CF). All of these diseases can progress to cirrhosis. The goals of the ChiLDReN network are to follow large numbers of these subjects longitudinally to allow accumulation of clinical data and biospecimens for studies that can help diagnose, use biomarkers to prognosticate for, and treat these diseases. Translational research founded on this remarkable database and biorepository can result in new insights regarding pathogenesis, disease modifiers, and ultimately therapy. We propose to continue participation in the ChiLDReN Research Network; our center will recruit patients with ChiLDReN diseases aggressively, retain them for longitudinal follow-up, and contribute to ongoing studies. We will continue to actively participate in the IMAGINE clinical trial studying the effect of an intestinal bile-acid transport inhibitor on pruritus. We will continue to participate in the longitudinal FORCE study of transient elastography to monitor hepatic fibrosis in children with biliary atresia, A1AT, and ALGS. The CF studies will continue to evaluate the role of ultrasound in predicting the development of cirrhosis in children with CF (PUSH), the role of transient elastography (ELASTIC), and magnetic resonance elastography (MRE) to non-invasively monitor fibrosis progression, and the progression of cirrhosis in this disease. We will participate in the development and implementation of the Primary Sclerosing Cholangitis (PSC) study, beginning with a database study and progressing to a clinical trial. The ultimate goal of the network is to learn more about natural history and pathogenesis in order to inform therapy and clinical management of cholestatic diseases in children. The Pilot and Feasibility clinical trial proposed by the IU center is a study of Minimal Hepatic Encephalopathy (MHE) in children with cirrhosis/portal hypertension due to biliary atresia. A panel of neurocognitive tests of executive function and a parent survey instrument will be used to evaluate children with biliary atresia-related cirrhosis. Children who are diagnosed with MHE will participate in a clinical trial of lactulose therapy, acting as their own control, with repeat neurocognitive testing after 3 months. ChiLDReN data will be used to begin to examine risk factors for the condition. This pilot will generate data about the frequency of this important sequela of chronic liver disease and guide future multicenter studies investigating its treatment.

项目概要/摘要 小儿肝病具有显着的发病率和死亡率。胆道闭锁（BA）占 一半的儿童肝移植。新生儿胆汁淤积的遗传原因包括阿拉吉尔综合征 (ALGS)、α-1 抗胰蛋白酶缺乏症 (A1AT)、进行性家族性肝内胆汁淤积症 (PFIC)、胆汁 酸合成缺陷、线粒体肝病和囊性纤维化 (CF)。所有这些疾病都可以 进展为肝硬化。 ChiLDReN 网络的目标是追踪大量此类主题 纵向收集临床数据和生物样本以进行有助于诊断的研究， 使用生物标志物来预测和治疗这些疾病。以此为基础的转化研究 卓越的数据库和生物样本库可以带来关于发病机制、疾病的新见解 修饰剂，最终是治疗。我们建议继续参与儿童研究 网络;我中心将积极招募儿童疾病患者，长期保留 跟进并为正在进行的研究做出贡献。我们将继续积极参与IMAGINE 研究肠道胆汁酸转运抑制剂对瘙痒症影响的临床试验。我们将继续 参与瞬时弹性成像监测儿童肝纤维化的纵向FORCE研究 患有胆道闭锁、A1AT 和 ALGS。 CF 研究将继续评估超声在 预测 CF 儿童肝硬化的发展（PUSH），瞬时弹性成像的作用 （ELASTIC）和磁共振弹性成像（MRE）以非侵入性监测纤维化进展， 以及这种疾病的肝硬化进展。我们将参与开发和实施 原发性硬化性胆管炎 (PSC) 研究的一部分，从数据库研究开始，逐步发展到 临床试验。该网络的最终目标是更多地了解自然历史和发病机制 旨在为儿童胆汁淤积性疾病的治疗和临床管理提供信息。 印第安纳大学中心提出的试点和可行性临床试验是一项针对微小肝病的研究 由于胆道闭锁而导致肝硬化/门静脉高压症的儿童发生脑病（MHE）。一个面板 将使用执行功能的神经认知测试和家长调查工具来评估儿童 与胆道闭锁相关的肝硬化。被诊断患有 MHE 的儿童将参加临床试验 乳果糖治疗，作为自己的对照，3个月后重复神经认知测试。 ChiLDReN 数据将用于开始检查该病症的风险因素。该试点将生成数据 了解慢性肝病这一重要后遗症的发生频率并指导未来的多中心研究 研究其治疗方法。