Childhood Liver Disease Research Network (ChiLDReN) Clinical Centers

项目摘要/摘要 肝病是婴幼儿发病率和死亡率的主要原因。这些疾病 由“儿科肝病”组成的疾病是个别罕见的，这阻碍了对其 病因/病理生理学。由于对有效治疗的理解存在这一基本缺陷 他们中的大多数都缺乏战略。这反过来又导致许多儿童进展到 终末期肝病需要进行原位肝移植。儿童肝移植 约占所有进行的肝脏移植的10%，大部分的适应症 它们属于儿童肝病研究网络要研究的疾病之一 (儿童)。这个网络结合了几个大的和个别成功的网络的努力 临床研究企业招募受试者并进行严格的临床研究 以及试验，期望建立具有良好特征的患者队列，这些患者可以 跟踪他们的疾病过程的自然历史，并可以访问 新兴疗法的试验。此外，与临床数据相联系的生物标本提供了 病因学研究的燃料(遗传和其他)以及基因表达和 关于疾病表达和进展的表观基因组学，以及对治疗的反应。我们 建议将儿童问题作为一个研究人员拥有大量专业知识的中心参与 在整个财团内部的几个关键调查领域。我们中心有 在这一学期里，我是儿童研究课题的主要贡献者之一 它的存在。我们预计将继续为以下方面的表现做出重大贡献 儿童在实现其成功消除儿童肝病目标方面的主要工作 婴幼儿发病率和死亡率的原因。我们中心的具体目标包括：a) 作为领先的儿童临床中心全面参与；b)试点双盲， 随机、安慰剂对照、交叉试验测试利福昔明治疗 减轻轻度肝性脑病(MHE)症状改善健康相关问题 儿童门户网络中学龄儿童患者的生活质量研究 高血压(PHTN)；c)确定全身炎症标志物和 学龄期细菌移位对PRO和生长激素轴的影响 患有和不患有PHTN的儿童。

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.