Center for the Study of Pediatric Cholestasis

小儿胆汁淤积研究中心

基本信息

批准号：
8011666
负责人：
Nanda Kerkar
金额：
$ 15万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-02-01 至 2012-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8011666
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 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 operation outcome forecast prevent programs prospective repository therapy development web site

项目摘要

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）：这一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明确儿童主要胆汁淤积性肝病的流行病学、临床特征和病理生理学，并开发新疗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) 门肠造口术后皮质类固醇试验，b) 获取有关流行病学、临床特征、影响门肠造口术后结果的因素的新信息，以及胆道闭锁的组织病理学，c) 定义修饰基因在影响结果中的作用，以及 d) 开发新疗法来减轻或预防胆道闭锁的发展门肠造口术后胆汁性肝硬化；目标 2) 研究遗传性肝内胆汁淤积的自然史、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;目标 3) 确定线粒体肝病的总体频率、完整临床谱和自然史。对于所有研究，血清、尿液、组织和 DNA 样本的存储库将可供未来的辅助研究使用。 ChiLDREN 内部的基础设施和合作为年轻研究者提供了独特的培训机会。小额试点拨款和示范项目将允许测试新的假设，从而可以通过独立拨款或涉及所有 ChiLDREN 中心的更大规模研究，从美国国立卫生研究院获得更多资金。还需要通过我们的出版物和网站提高初级保健医生和普通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，并且与显着的发病率、死亡率和肝移植的需要相关。 ChiLDREN 项目将产生有关这些疾病的临床特征和原因的新知识，并开发治疗方法来改善和延长这些患者的生命。