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）：这种竞争性更新应用的目的是继续，扩展和合并胆道闭锁研究联盟（BARC）和胆汁淤积的肝财团（CLIC），以形成儿童肝病研究和教育网络（儿童）。儿童将具有进一步定义主要胆汁淤积性肝脏疾病的流行病学，临床特征和病理生理学的总体目标，并开发出新的疗法以改善和延长这些患者的寿命。 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)开发新的疗法，以减弱或防止港口造口后胆道肝硬化的发展；目的2）研究自然史，临床特征，基因型与表型的相关性以及包括阿拉吉尔综合征在内的遗传内胆汁淤积的遗传形式的预后，α-1-抗抗肽缺乏症，渐进的家族性家族性肝内胆汁淤积（PFIC）和胆汁酸合成;目标3）确定线粒体肝病的整体频率，完整的临床光谱和自然历史。对于所有研究，将在未来的辅助研究中使用血清，尿液，组织和DNA标本的存储库。儿童内部的基础设施和合作为年轻调查人员提供了独特的培训机会。小型飞行员赠款和示范项目将允许对新的假设进行检验，这可能会通过独立的赠款或涉及所有儿童中心的大型研究从美国国家卫生研究院获得更多的大量资金。还需要通过我们的出版物和网站提高公众对小儿肝病和外行公众的认识。相关性：胆道闭锁和一组遗传性胆汁淤积综合征仍然很少理解，并且与肝脏静脉的明显发病率，死亡率和需求有关。儿童计划将提供有关这些疾病的临床特征和原因的新知识，并开发疗法以改善和延长这些患者的寿命。