Center for the Study of Pediatric Cholestasis

小儿胆汁淤积研究中心

• 批准号: 7743241
• 负责人: FREDERICK J SUCHY
• 金额: $ 30.95万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7743241
• 关键词: Acids; Adrenal Cortex Hormones; Adult; Affect; Aftercare; Alagille Syndrome; Ancillary Study; Attenuated; Awareness; Bile Acid Biosynthesis Pathway; Bile Acids; Bile fluid; Biliary; Biliary Atresia; Biliary cirrhosis; Biological Markers; Bone Density; Characteristics; Child; Childhood; Cholestasis; Cirrhosis; Clinical; Clinical Data; Clinical Trials; Collaborations; DNA; Data; Defect; Development; Diagnosis; Disease; Disease Progression; Drainage procedure; Education; Embryo; Etiology; Fibrosis; Frequencies; Functional disorder; Funding; Future; Genes; Genetic; Genotype; Goals; Grant; Hepatocyte; Histopathology; Infant; Inherited; Intrahepatic Cholestasis; Knowledge; Lead; Left; Life; Liver; Liver diseases; Longitudinal Studies; Mitochondria; Morbidity - disease rate; Mutation; Natural History; Operative Surgical Procedures; Outcome; Patients; Pharmaceutical Preparations; Phase; Phenotype; Primary Care Physician; Principal Investigator; Progressive intrahepatic cholestasis; Protein C Inhibitor; Publications; Recruitment Activity; Research; Research Infrastructure; Research Personnel; Respiratory Chain; Role; Serum; Single Nucleotide Polymorphism; Specimen; Syndrome; Testing; Tissues; Training; Treatment outcome; United States National Institutes of Health; Urine; Ursodeoxycholic Acid; Work; alpha 1-Antitrypsin Deficiency; bile duct; choleretic; clinical epidemiology; clinical phenotype; disorder subtype; double-blind placebo controlled trial; drug candidate; fatty acid oxidation; genome wide association study; improved; liver transplantation; mortality; novel; novel diagnostics; outcome forecast; prevent; programs; prospective; repository; therapy development; web site

DESCRIPTION (provided by applicant): The purpose of this competing renewal application is to continue, expand and merge the Biliary Atresia Research Consortium (BARC) and the Cholestatic Liver Consortium (CLiC) to form the Childhood Liver Disease Research and Education Network (ChiLDREN). ChiLDREN will have as its overall objectives to further define the epidemiology, clinical features, and pathophysiology of the major cholestatic liver diseases afflicting children, and develop new therapies to improve and prolong the life of these patients. The proposal consists of the following Specific Aims: Aim 1) Continue with the work of the Biliary Atresia Research Consortium: a) the trial of corticosteroids post portoenterostomy, b) acquire new information on epidemiology, clinical features, factors affecting outcome post portoenterostomy, and histopathology of biliary atresia, c) define the role of modifier genes in influencing outcome, and d) develop new therapies to attenuate or prevent the development of biliary cirrhosis post portoenterostomy; Aim 2) Study the natural history, clinical features, the correlation of genotype with phenotype, and prognosis of inherited forms of intrahepatic cholestasis including Alagille syndrome, alpha-1-antitrypsin deficiency, progressive familial intrahepatic cholestasis (PFIC), and bile acid synthesis defects; and Aim 3) Determine overall frequency, full clinical spectrum and natural history of the mitochondrial hepatopathies. For all studies a repository of serum, urine, tissue, and DNA specimens will be available for use in future ancillary studies. The infrastructure and collaborations within ChiLDREN offer unique training opportunities for young investigators. Small pilot grants and demonstration projects will allow new hypotheses to be tested that could lead to more substantial funding from the National Institutes of Health through an independent grant or a larger study involving all of the ChiLDREN centers. There is also a need to increase public awareness about pediatric liver disease to primary care physicians and the lay public through our publications and website. Relevance: Biliary atresia and a group of inherited cholestatic syndromes remain poorly understood, and are associated with significant morbidity, mortality, and need for liver tranplantation. The ChiLDREN program will produce new knowledge on the clinical features and causes of these diseases, and develop therapies to improve and prolong the life of these patients.

描述（由申请人提供）： 这项竞争性更新申请的目的是继续，扩大和合并胆道闭锁研究联盟（BARC）和胆汁淤积性肝脏联盟（CLiC），以形成儿童肝病研究和教育网络（ChiLDREN）。ChiLDREN的总体目标是进一步确定影响儿童的主要胆汁淤积性肝病的流行病学，临床特征和病理生理学，并开发新的治疗方法来改善和延长这些患者的生命。该提案包括以下具体目标：目标1）继续胆道闭锁研究联盟的工作：a）门肠吻合术后皮质类固醇的试验，B）获得关于流行病学、临床特征、影响门肠吻合术后结果的因素和胆道闭锁的组织病理学的新信息，c）定义修饰基因在影响结果中的作用，和d）开发新的疗法以减轻或预防门肠吻合术后胆汁性肝硬化的发展;目的2）研究遗传性肝内胆汁淤积症的自然史、临床特征、基因型与表型的相关性以及预后，包括Alagille综合征、α-1-抗胰蛋白酶缺乏症，进行性家族性肝内胆汁淤积（PFIC）和胆汁酸合成缺陷;和目的3）确定线粒体肝病的总体频率、全部临床谱和自然史。对于所有研究，将提供血清、尿液、组织和DNA标本的储存库，供未来的辅助研究使用。ChiLDREN内部的基础设施和合作为年轻的研究人员提供了独特的培训机会。小型试点赠款和示范项目将允许新的假设进行测试，这可能会导致更多的资金从美国国立卫生研究院通过一个独立的赠款或一个更大的研究，涉及所有的儿童中心。还需要通过我们的出版物和网站向初级保健医生和普通公众提高公众对儿科肝病的认识。 相关性：胆道闭锁和一组遗传性胆汁淤积综合征仍然知之甚少，并与显着的发病率，死亡率和肝移植的需要。ChiLDREN计划将产生关于这些疾病的临床特征和原因的新知识，并开发治疗方法以改善和延长这些患者的生命。