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

描述(由申请人提供)： 儿科肝病的发病率和死亡率都很高。胆道闭锁占儿童肝移植手术的一半以上。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、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变和终末期肝病。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，进行儿童肝病的临床研究，具体目标如下：具体目标1：为胆道闭锁研究联盟(BARC)、淤胆性肝病研究联盟(CLIC)和囊性纤维化肝病研究联盟(CFLD)的现有研究做出贡献，这三个研究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的试验。假说是糖皮质激素改善胆道闭锁Kasai手术的结果。具体目标2：我们将开展儿童门脉高压症的研究：我们将研究肝硬变儿童轻度肝性脑病(MHE)的发生率，评估他们与健康相关的生活质量(QOL)，并评估乳果糖治疗对MHE的影响。假设是MHE在儿童中很常见，对生活质量有负面影响，乳果糖可以改善MHE和QOL。我们将进行一项关于静脉曲张破裂出血二级预防的随机对照试验，比较内窥镜套扎术(EBL)和心得安。假设EBL在儿童静脉曲张出血的二级预防中优于心得安。具体目标3：我们将设计和实施一个计算机模块，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前后测试初级保健提供者和住院医生来评估我们的结果。假设新生儿胆汁淤积症的计算机模块的使用提高了初级保健医生的知识。 相关性：儿童肝病与慢性病、营养不良和需要肝移植有关，对公众健康有重大影响。对于生理学、诊断、自然病史、危险因素和治疗方面的知识是非常需要的。由于这些疾病是罕见的，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疾病是至关重要的。

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.