Clinical Research on Nonalcoholic Fatty Liver Disease

描述(由申请人提供)：哥伦比亚大学的非酒精性脂肪性肝炎临床研究网络(NASH CRN)及其位于加州大学圣地亚哥分校的分包网站在过去12年中在促进儿童和成人对非酒精性脂肪性肝病的理解方面发挥了重要作用。鉴于NAFLD是美国最常见的慢性肝病，已知的预后包括肝硬化、肝移植和肝癌，我们必须开发更好的非侵入性方法来诊断更严重或进展性的NAFLD，并找到具有独特和合理靶点的改进治疗方法。这项针对我们临床中心的有限竞争更新提案展示了在纵向数据库研究方面取得的进展，以及在过去和当前/正在进行的成人和儿童随机临床试验(分别为Flint和CyNCH)中的重要发现。我们的中心和网络描述了完成和继续发展临床试验的计划，寻找新的生物成像方法来评估治疗反应，并完成和发展辅助研究，以了解遗传和环境因素在调节疾病过程中的作用。在这方面，我们领导了对患有NAFLD的西班牙裔男孩进行全基因组关联扫描的研究，认识性类固醇和核激素受体在脂肪变性、炎症和细胞损伤中的作用，以及阐明肠道微生物群在儿童NAFLD中的作用。我们打算继续在NASH CRN中发挥领导作用，因为PI是指导委员会和数据库委员会的联合主席，执行委员会的成员，以及儿科委员会的主席。我们中心在招生方面的领导作用，以及我们在NASH CRN招募和留住儿童和少数族裔方面的领导作用，预计将通过完成当前的试验和启动新的拟议研究而继续下去。

DESCRIPTION (provided by applicant): The Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) at Columbia University and its subcontracted sites at the University of California, San Diego have played a major role over the past 12 years in furthering the understanding of nonalcoholic fatty liver disease in children and adults. Given that NAFLD is the most common chronic liver disease in the United States and that known outcomes include cirrhosis, liver transplant and liver cancer, it is imperative that we develop better noninvasive measures to diagnose with more severe or progressive forms of NAFLD and that we find improved therapies with unique and rational targets. The proposal in this limited competition renewal for our Clinical Center demonstrates the progress made in longitudinal database studies and significant findings in past and current/ongoing randomized clinical trials in adults and children (FLINT and CyNCh, respectively). Our Center and the Network describe plans for completion and continued development of clinical trials, for finding novel bio-imaging methods to assess response to therapy and to complete and develop ancillary studies for understanding the role of genetic and environmental factors in modulating the course of disease. In this regard, we lead studies in genome-wide association scans in Hispanic boys with NAFLD, in recognizing the role of sex steroids and nuclear hormone receptors in steatosis, inflammation and cell injury; and in elucidating the role of the gut microbiome in pediatric NAFLD. We intend to continue to play leading roles in the NASH CRN, as the PI is Co-Chair of the Steering Committee and Database Committee, a member of the Executive Committee, and Chair of the Pediatric Committee. Our Centers' leading role in enrollment, along with our leadership in recruitment and retention of children and minorities in the NASH CRN are expected to continue through completion of current trials and initiation of newly proposed studies.