Childhood Liver Disease Research Network (ChiLDReN) Clinical Centers

项目总结/摘要 肝病是婴儿和儿童发病率和死亡率的主要原因。的疾病 包括“儿科肝病”的个体罕见，这阻碍了他们的研究。 病因/病理生理学。由于这一基本缺陷，在理解有效的治疗， 大多数国家缺乏战略。这反过来又导致许多儿童发展到 终末期肝病需要原位肝移植。小儿肝移植 包括大约10%的所有肝移植手术，并且大多数肝移植手术的适应症 它们是儿童肝病研究网络要研究的疾病之一。 （ChiLDReN）.这个网络结合了几个大的和个别成功的努力， 临床研究企业招募受试者并进行严格的临床研究 和试验，期望建立特征良好的患者队列， 通过他们的疾病过程的自然历史，可以访问， 新兴疗法的试验此外，与临床数据相关的生物标本提供了 研究病因学（遗传和其他）和基因表达的影响的燃料， 表观基因组学对疾病表达和进展，以及对治疗的反应。我们 我建议参加ChiLDReN作为一个中心，其中研究者具有丰富的专业知识 在整个财团的几个关键调查领域。我中心 在本学期内，我是ChiLDReN进行的研究的主要贡献者之一。 它的存在。我们希望继续为业绩作出重大贡献， ChiLDReN在实现其成功消除儿科肝病作为主要疾病的目标方面 婴儿和儿童发病率和死亡率的原因。我们中心的具体目标包括： 充分参与作为一个领先的临床中心在儿童疾病; B）试点双盲， 随机、安慰剂对照、交叉试验，测试利福昔明治疗对 减轻轻微肝性脑病（MHE）的症状，改善健康相关 ChiLDReN网络中学龄期患者的生活质量（HRQOL） c）表征全身炎症标志物的影响，以及 学龄儿童PRO和生长激素轴上细菌移位的测量 有和没有PHTN的孩子

Project Summary/Abstract Liver disease is a major cause of infant and childhood morbidity and mortality. The diseases comprising “pediatric liver diseases” are individually rare, which has hindered the study of their causes/pathophysiologies. As a result of this basic defect in understanding effective therapeutic strategies are lacking for most of them. This in turn results in many children with progressing to end-stage liver disease necessitating orthotopic liver transplantation. Pediatric liver transplants comprise approximately 10% of all liver transplants performed, and the indications for most of them lie among the diseases to be studied in the Childhood Liver Disease Research Network (ChiLDReN). This network combines the efforts of several large and individually successful clinical research enterprises to recruit subjects and carry them through rigorous clinical studies and trials with the expectation of establishing well-characterized patient cohorts that can be followed through the natural history of their disease process and which can be accessed for trials of emerging therapies. In addition, the biological specimens linked to clinical data provide the fuel for studies of etiology (genetic and other) and the influences of gene expression and epigenomics on disease expression and progression, as well as response to therapy. We propose to participate in ChiLDReN as a center wherein investigators have substantial expertise in several of the key areas of investigation within the consortium as a whole. Our center has been one of the top contributors of subjects to studies undertaken by ChiLDReN over the term of its existence. We expect to continue to contribute substantially to the performance of ChiLDReN in achieving its goal of successfully eliminating pediatric liver disease as a major cause of infant and childhood morbidity and mortality. The specific aims at our center include: a) to participate fully as a leading clinical center in ChiLDReN; b) To pilot a double-blind, randomized, placebo controlled, cross-over trial testing the efficacy of rifaximin therapy to reduce symptoms of minimal hepatic encephalopathy (MHE) and improve Health Related Quality of Life (HRQOL) in school aged patients in the ChiLDReN network with portal hypertension (PHTN); c) To characterize the impact of systemic inflammatory markers and measures of bacterial translocation on both PROs and the growth hormone axis in school age children with and without PHTN.