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发生的最重要的肝脏疾病之一，导致严重的发病率，占儿童期肝移植的 70% 以上，构成重大的公共卫生负担。在胆汁淤积中，胆汁流动受损会导致肝毒性胆汁酸、胆固醇和其他化合物的积累，从而产生肝损伤和并发症，例如瘙痒和黄色瘤；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、门静脉高压并最终导致慢性肝衰竭。对这些疾病的研究有望推进有关肝脏发育、病理生理学和损伤机制的科学知识，以及疾病生物标志物的发现以及新诊断和治疗策略的开发和测试。过去 6 年，我们中心胆道闭锁研究联盟 (BARC) 和胆汁淤积性肝病联盟 (CLiC) 对一组疾病进行了研究，包括胆道闭锁、特发性新生儿肝炎、α-抗胰蛋白酶缺乏症、 Alagille 综合征、进行性家族性肝内胆汁淤积、胆汁酸合成缺陷、线粒体肝病，以及最近的囊性纤维化肝病。科罗拉多大学丹佛分校和儿童医院的 BARC 和 CLiC 临床中心的成员发挥了重要的领导作用，担任 BARC 指导委员会主席、CLiC 首席研究员和主席以及 CFLD 研究主席。该拨款申请的目标是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；继续招募参与者并全面实施、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；参与网络发起的所有新的研究、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；参与研究员培训和公众教育；作为ChiLDREN 的行政核心；并继续作为遗传核心和呼吸链核心之一。通过这种方式，我们的临床中心将参与 ChiLDREN 的目标，即为患有胆汁淤积性肝病的儿童发现新的诊断、病因和治疗方案，并培训下一代儿科肝病研究人员。 相关性：这项研究将有助于为患有肝病的儿童和接受肝移植的儿童发现新的诊断测试和治疗方法。我们还将培训未来研究这些罕见疾病的研究人员。