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、自然病史和治疗相关的研究。NASH CRN在建立和进行全网络临床试验以及许多辅助和先导性研究方面卓有成效。NIDDK受到其成功的鼓舞，发布了RFA-DK-13-503，其目标是将NASH CRN再延续五年。NASH CRN在下一个资助期的目标是：(A)成功完成在上一个资助期启动的三项全网临床试验和研究。其中包括一项观察性的纵向研究。 一项成人和儿童NAFLD的随机双盲对照研究(Flint，n=283)，以及一项儿童NAFLD的随机双盲对照治疗研究(CyNCH，n=160)。将对NAFLD数据库研究进行修订，以满足下一个供资期间的额外目标。这些修改可能包括延长受试者的随访时间，考虑在部分非肝硬变患者中进行后续肝活检，基于病例定义的判定结果评估，以及为生物标记物研究招募精心选择的没有NAFLD的对照：(B)成功完成正在进行的大型先导性和辅助研究，(C)对患有NAFLD的成人和儿童进行额外的治疗性研究 NASH作为目前可用于治疗NASH的选择相当有限，以及(D)基于迄今收集的大量临床材料和生物样本启动和完成额外的辅助研究。这些研究可能集中在(但不限于)儿童和成人的NAFLD和NASH的自然病史、疾病严重性的非侵入性评估(例如，生物标记物的开发、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)。如有需要，将寻求外部专业知识。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.