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）：小儿肝病具有显着的发病率和死亡率。胆道闭锁占小儿肝移植的一半以上。新生儿胆汁淤积的遗传原因包括阿拉吉尔综合征、α-1-抗胰蛋白酶缺乏、进行性家族性肝内胆汁淤积 (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，开展儿童肝病的临床研究，具体目标如下：具体目标 1：为胆道闭锁的现有研究做出贡献研究联盟 (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) 正在合并，组成儿童网。研究将包括收集和研究患有这些疾病的儿童的临床数据、评估诊断测试以及存储生物样本以供未来研究。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试验。该假设是皮质类固醇可以改善胆道闭锁 Kasai 手术的结果。具体目标2：我们将开展儿童门静脉高压研究：我们将研究肝硬化儿童中最小肝性脑病（MHE）的发生频率，评估他们的健康相关生活质量（QOL），并评估乳果糖治疗的影响关于 MHE。假设 MHE 在儿童中很常见，会对生活质量产生负面影响，而乳果糖可以改善 MHE 和生活质量。我们将进行一项静脉曲张出血二级预防的随机对照试验，比较内镜套扎术 (EBL) 与普萘洛尔。假设 EBL 对于儿童静脉曲张出血的二级预防优于普萘洛尔。具体目标3：我们将设计并实现一个计算机模块，向医生传授有关新生儿胆汁淤积的要点；我们将通过在使用课程之前和之后测试初级保健提供者和居民来评估我们的结果。假设使用计算机模块治疗新生儿胆汁淤积可以提高初级保健医生的知识。相关性：小儿肝病与慢性病、营养不良和肝移植的需要相关，对公共健康具有重大影响。非常需要有关生理学、诊断、自然史、危险因素和治疗的知识。由于这些疾病很罕见，因此像儿童网络这样的多中心合作对于研究这些儿童以及改善医疗管理和结果至关重要。