Colorado Center for Childhood Liver Disease Research and Education

科罗拉多儿童肝病研究和教育中心

• 批准号: 8028769
• 负责人: RONALD J. SOKOL
• 金额: $ 14.35万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-10 至 2012-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8028769
• 关键词: Accounting; Adrenal Cortex Hormones; Alagille Syndrome; Ancillary Study; Applications Grants; Award; Bile Acid Biosynthesis Pathway; Bile Acids; Bile fluid; Biliary Atresia; Biological Markers; Child; Childhood; Cholestasis; Cholesterol; Chronic; Clinical; Clinical Research; Clinical Trials; Clinical trial protocol document; Colorado; Communities; Cystic Fibrosis; Data; Defect; Development; Diagnostic tests; Disease; Education; Educational Materials; Enrollment; Etiology; Evaluation; Fat-Soluble Vitamin; Fatty acid glycerol esters; Fellowship; Functional disorder; Future; Genetic; Goals; Impairment; Infant; Injury; Investigation; Knowledge; Laboratories; Leadership; Liver; Liver Failure; Liver Fibrosis; Liver diseases; Longitudinal Studies; Malabsorption Syndromes; Malnutrition; Mitochondria; Morbidity - disease rate; Outcome; Participant; Pediatric Hospitals; Pilot Projects; Play; Portal Hypertension; Principal Investigator; Progressive intrahepatic cholestasis; Protein C Inhibitor; Protocols documentation; Pruritus; Public Health; Publications; Publishing; Rare Diseases; Research; Research Infrastructure; Research Personnel; Research Training; Respiratory Chain; Role; Scientific Advances and Accomplishments; Specimen; Testing; Therapeutic; Training; Training and Education; Ultrasonography; Universities; Xanthomas; data acquisition; follow-up; liver transplantation; member; neonatal hepatitis; next generation; novel diagnostics; patient advocacy group; programs; prospective; public education; research study; web site

DESCRIPTION (provided by applicant): Cholestatic liver diseases are among the most important liver disorders that occur in infants and children, leading to devastating morbidity and accounting for over 70% of liver transplants performed during childhood, posing a major public health burden. In cholestasis, impairment of bile flow leads to the accumulation of hepatotoxic bile acids, cholesterol and other compounds that produce liver injury and complications such as pruritus and xanthomas; nutritional deficiencies caused by fat and fat-soluble vitamin malabsorption; and progressive hepatic fibrosis, portal hypertension and eventually chronic liver failure. Investigation of these disorders promises to advance scientific knowledge about liver development, pathophysiology and mechanisms of injury, as well as the discovery of biomarkers of disease and development and testing of new diagnostic and therapeutic strategies. A group of these disorders has been studied at our Center for the past 6 years within the Biliary Atresia Research Consortium (BARC) and the Cholestatic Liver Disease Consortium (CLiC), and include biliary atresia, idiopathic neonatal hepatitis, alpha- i-antitrypsin deficiency, Alagille syndrome, progressive familial intrahepatic cholestasis, bile acid synthesis defects, mitochondrial hepatopathies, and, most recently, cystic fibrosis liver disease. Members of our BARC and CLiC Clinical Centers at the University of Colorado Denver and The Children's Hospital have played major leadership roles as the Chair of the Steering Committee of BARC, the Principal Investigator and Chair of CLiC, and the Study Chair for the CFLD studies. The obiectives of this grant application are to become a Clinical Center and Administrative Core in the newly merged Childhood Liver Disease Research and Education Network; to continue to enroll participants and fully implement, complete and publish all of the ongoing BARC and CLiC study protocols, including the corticosteroid trial in biliary atresia; to participate in all new investigations, protocols and clinical trials initiated by the Network; to develop and propose new clinical studies and ancillary/pilot studies; to participate in training of research fellows and education of the public; to function as the Administrative Core of ChiLDREN; and to continue as one of the Genetic Cores and the Respiratory Chain Core. In this way, our Clinical Center will participate in the ChiLDREN goals of discovering new diagnostics, etiologies and treatment options for children with cholestatic liver diseases and to train the next generation of investigators in pediatric liver diseases. Relevance: This study will help to discover new diagnostic tests and treatments for children with liver disease and those who undergo liver transplantation. We will also train the researchers of the future who will study these rare diseases.

描述（由申请人提供）： 胆汁淤积性肝病是婴儿和儿童中最重要的肝病之一，导致灾难性的发病率，占儿童期间进行的肝脏移植物的70％以上，造成了重大的公共卫生负担。在胆汁淤积中，胆汁流的损害会导致肝毒性胆汁酸，胆固醇和其他产生肝损伤以及并发症（如瘙痒和Xanthomas）的化合物的积累；由脂肪和脂溶性维生素吸收不良引起的营养缺乏；以及进行性肝纤维化，门静脉高压和最终慢性肝衰竭。对这些疾病的调查有望提高有关肝脏发育，病理生理学和损伤机制的科学知识，以及发现疾病的生物标志物，发展以及对新的诊断和治疗策略的测试。在过去的6年中，在我们的中心研究了一组这些疾病，在胆道性闭锁研究联盟（BARC）和胆汁疾病肝病联盟（CLIC）中，包括胆道性闭锁，特发性新生儿肝炎缺陷，线粒体肝病以及最近的囊性纤维化肝病。我们在科罗拉多大学丹佛大学和儿童医院的BARC和CLIC临床中心的成员担任BARC指导委员会主席，CLIC首席研究员和CLIC主席以及CFLD研究主席的主要领导职务。该赠款申请的构造措施将成为新合并的儿童肝病研究和教育网络中的临床中心和行政核心；继续招募参与者并充分执行，完成和发布所有正在进行的BARC和CLIC研究方案，包括胆道闭锁的皮质类固醇试验；为了参与所有新调查，该网络发起的方案和临床试验；开发和提出新的临床研究和辅助/试点研究；参加研究研究员和公众教育的培训；充当儿童的行政核心；并继续作为遗传核心之一和呼吸链核心之一。这样，我们的临床中心将参与儿童目标，即发现胆固性肝病儿童的新诊断，病因和治疗方案，并培训下一代儿科肝病研究人员。 相关性：这项研究将有助于发现针对肝病儿童以及接受肝移植的儿童的新诊断检查和治疗方法。我们还将培训未来研究这些罕见疾病的研究人员。