Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN)

描述（由申请人提供）：非酒精性脂肪性肝病（NAFLD）是美国慢性肝病的常见原因。它包括脂肪肝和非酒精性脂肪性肝炎（NASH）。NASH临床研究网络（NASH CRN）成立于2002年，旨在开展与儿童和成人NAFLD的临床特征、自然史和治疗相关的研究。NASH CRN在建立和开展网络范围的临床试验以及许多辅助和试点研究方面非常富有成效。受其成功的鼓舞，NIDDK发布了RFA-DK-13-503，其目标是将NASH CRN再延续五年。NASH CRN在下一个资助期内的目标是：（a）成功完成上一个资助期内启动的三项网络范围的临床试验和研究。其中包括一项观察性纵向研究 成人和儿童NAFLD的随机双盲对照治疗研究（NAFLD数据库1和2）、成人NASH患者中奥贝胆酸的随机双盲对照治疗研究（FLINT，n=283）和儿童NAFLD的随机双盲对照治疗研究（CyNCH，n=160）。NAFLD数据库研究将在下一个资助期内进行修改，以满足其他目标。这些修改可能包括延长入组患者的随访时间，考虑在无肝硬化的患者亚组中进行随访肝活检，裁定的基于病例定义的结局评估，以及招募精心选择的无NAFLD的对照进行生物标志物研究（B），以成功完成正在进行的大量初步和辅助研究，（c）对患有下列疾病的成人和儿童进行更多的治疗研究： NASH作为目前可用于治疗NASH的选择是相当有限的，并且（d）基于迄今为止收集的广泛的临床材料和生物样品启动并完成额外的辅助研究。这些研究可能集中于（但不限于）儿童和成人NAFLD和NASH的自然史，疾病严重程度的非侵入性评估（例如，生物标志物开发、放射学评估）和疾病发病机制（细胞因子分析、全基因组关联研究、系统生物学）。必要时将寻求外部专家。因此，NASH CRN将完成NIH针对NAFLD的大部分肝脏行动计划。

DESCRIPTION (provided by applicant): Nonalcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease in the United States. It encompasses both a fatty liver and nonalcoholic steatohepatitis (NASH). The NASH Clinical Research Network (NASH CRN) was established in 2002 to conduct research related to the clinical features, natural history and treatment of NAFLD in children and adults. The NASH CRN has been very productive in establishing and conducting network-wide clinical trials and numerous ancillary and pilot studies. Encouraged by its success, the NIDDK has issued RFA-DK-13-503 whose objective is to continue the NASH CRN for additional five years. The objectives of the NASH CRN during the next funding period are (a) to successfully complete three network-wide clinical trials and studies initiated during the last funding period. These include an observational longitudinal study of NAFLD in adults and children (NAFLD Database 1 and 2), a randomized double blind controlled therapeutic study of obeticholic acid in adults with NASH (FLINT, n=283), and a randomized double blind controlled therapeutic study of NAFLD in children (CyNCH, n=160). The NAFLD Database study will be amended to meet additional goals during the next funding period. These modifications may include extending the length of follow-up of those enrolled, consideration of a follow-up liver biopsy in a subset of patients without cirrhosis, adjudicated case-definition based outcomes assessment and enrolling carefully chosen controls without NAFLD for biomarker studies (b) to successfully complete a large set of pilot and ancillary studies that are ongoing, (c) to conduct additional therapeutic studies in adults and children with NASH as options currently available to treat NASH are quite limited, and (d) to initiate and complete additional ancillary studies based on extensive clinical material and biosamples collected thus far. These studies may focus on (but not limited to) natural history of NAFLD and NASH in children and adults, non-invasive assessment of disease severity (e.g., biomarker development, radiologic assessment) and disease pathogenesis (cytokine analyses, genome-wide association studies, systems biology). External expertise will be sought as needed. The NASH CRN will thus accomplish most of the NIH liver action plan for NAFLD.