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Biliary Atresia, Cholestatic Liver Diseases, and Cystic Fibrosis: Indiana Univers

胆道闭锁、胆汁淤积性肝病和囊性纤维化：印第安纳大学

基本信息

批准号：
7743277
负责人：
Jean Pappas Molleston
金额：
$ 41.81万
依托单位：
INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-10 至 2014-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7743277
关键词：
Accounting Adrenal Cortex Hormones Alagille Syndrome Bile Acids Biliary Atresia Biological Biological Markers Bone Growth Child Childhood Cholestasis Chronic Disease Cirrhosis Clinical Clinical Data Clinical Research Collaborations Communities Computers Cystic Fibrosis Data Databases Defect Diagnosis Diagnostic tests Disease Disease Outcome Education Educational Curriculum Educational process of instructing Encephalopathies Enrollment Family Frequencies Future Genetic Genotype Hemorrhage Hepatic Hepatic Encephalopathy Indiana Knowledge Lactulose Ligation Liver Liver diseases Longitudinal Studies Malnutrition Medical Mitochondria Morbidity - disease rate Natural History Neonatal Operative Surgical Procedures Outcome Patients Phenotype Physicians Physiology Placebos Portal Hypertension Primary Care Physician Primary Health Care Principal Investigator Progressive intrahepatic cholestasis Prophylactic treatment Propranolol Protein C Inhibitor Provider Public Health Quality of life Randomized Controlled Trials Rare Diseases Research Risk Risk Factors Sampling Specimen Testing Ultrasonography alpha 1-Antitrypsin Deficiency children with cystic fibrosis clinical phenotype cognitive function cystic fibrosis patients design health related quality of life improved knowledge base liver transplantation mortality pediatrician repository

项目摘要

DESCRIPTION (provided by applicant): Pediatric liver disease has significant morbidity and mortality. Biliary atresia accounts for more than half of pediatric liver transplants. Genetic causes of neonatal cholestasis include Alagille's syndrome, alpha-1-antitrypsin deficiency, Progressive Familial Intrahepatic Cholestasis (PFIC), bile acid synthetic defects, mitochondrial hepatopathies, and cystic fibrosis. All of these diseases can progress to cirrhosis and endstage liver disease. In order to study the diagnosis, progression, and treatment of these disorders, we propose to join the CHILDREN Research Network to conduct clinical research on pediatric liver disease with the following specific aims: Specific Aim 1: Contribute to the existing studies in the Biliary Atresia Research Consortium (BARC), the Cholestatic Liver Diseases Research Consortium (CLiC) and Cystic Fibrosis Liver Disease Research Consortium (CFLD), which are merging to form the CHILDREN network. Research will include collecting and studying clinical data on children with these diseases, evaluating diagnostic tests, and storing biosamples for future study. We will enroll patients in the ongoing trial of corticosteroids for the treatment of biliary atresia. The hypothesis is that corticosteroids improve the outcome of Kasai operation in biliary atresia. Specific Aim 2: We will conduct studies of portal hypertension in children: We will study the frequency of minimum hepatic encephalopathy (MHE) in children with cirrhosis, assess their health-related quality of life (QOL), and evaluate the impact of lactulose therapy on MHE. The hypothesis is that MHE is common in children, negatively impacts QOL, and that lactulose improves MHE and QOL. We will conduct a randomized controlled trial of secondary prophylaxis of variceal bleeding comparing endoscopic band ligation (EBL) vs propranolol. The hypothesis is that EBL is superior to propranolol for secondary prophylaxis of variceal bleeding in children. Specific Aim 3: We will design and implement a computer module which teaches physicians key points about neonatal cholestasis; we will evaluate our outcomes by testing primary care providers and residents before and after using the curriculum. The hypothesis is that use of computer modules on neonatal cholestasis improves the knowledge of primary care physicians. Relevance: Pediatric liver disease, associated with chronic illness, malnutrition, and the need for liver transplantation, has significant public health impact. There is much need for knowledge regarding physiology, diagnosis, natural history, risk factors and treatment. Because these diseases are rare, multicenter collaborations like the CHILDREN network are crucial for studying these children and improving medical management and outcnmes.

描述（由申请人提供）：儿科肝病具有显著的发病率和死亡率。胆道闭锁占小儿肝移植的一半以上。新生儿胆汁淤积症的遗传原因包括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症（PFIC）、胆汁酸合成缺陷、线粒体肝病和囊性纤维化。所有这些疾病都可能发展为肝硬化和终末期肝病。为了研究这些疾病的诊断，进展和治疗，我们建议加入儿童研究网络，对儿科肝病进行临床研究，具体目标如下：具体目标1：为胆道闭锁研究联盟（BARC）、胆汁淤积性肝病研究联盟（CLiC）和囊性纤维化肝病研究联盟（CFLD）的现有研究做出贡献，他们正在合并形成儿童网络。研究将包括收集和研究患有这些疾病的儿童的临床数据，评估诊断测试，并储存生物样本供未来研究。我们将招募患者参加正在进行的皮质类固醇治疗胆道闭锁的试验。假设皮质类固醇改善胆道闭锁加塞手术的结果。具体目标二：我们将进行儿童门静脉高压症的研究：我们将研究肝硬化儿童最小肝性脑病（MHE）的发生率，评估其健康相关生活质量（QOL），并评价乳果糖治疗对MHE的影响。假设MHE在儿童中很常见，对QOL有负面影响，而乳果糖可改善MHE和QOL。我们将进行一项随机对照试验，比较内镜下套扎术（EBL）与普萘洛尔对静脉曲张出血的二级预防。假设EBL在儿童静脉曲张出血的二级预防方面上级优于普萘洛尔。具体目标3：我们将设计和实施一个计算机模块，教授医生关于新生儿胆汁淤积症的关键点;我们将通过测试初级保健提供者和居民使用课程前后来评估我们的结果。假设是，使用计算机模块对新生儿胆汁淤积症提高初级保健医生的知识。相关性：与慢性疾病、营养不良和肝移植需求相关的儿科肝病对公共卫生有重大影响。非常需要有关生理学，诊断，自然史，风险因素和治疗的知识。由于这些疾病很罕见，像儿童网络这样的多中心合作对于研究这些儿童和改善医疗管理和结果至关重要。