Clinical Research Network in Nonalcoholic Steatohepatitis

描述（由申请人提供）：本申请是为了延续弗吉尼亚梅森医学中心（VMMC）临床站点及其非酒精性脂肪性肝炎临床研究网络（NASH CRN）的子站点。非酒精性脂肪性肝病（NAFLD）影响北美三分之一的成年人和五分之一的儿童，在美国是一个日益严重的公共卫生问题。NAFLD，尤其是非酒精性脂肪性肝炎（NASH），可能导致终末期肝病和原发性肝癌，以及肝脏、心血管和癌症相关的死亡率，导致健康负担和成本的大幅增加。NASH CRN具有理想和独特的定位，可以影响NASH日益增长的公共卫生意义，这只能通过大型研究联盟来解决。NASH CRN的主要目标是开展成人和儿童NASH和NAFLD的临床研究。一个密切相关和高度优先的次要目标是开展NASH和NAFLD的转化研究，重点关注发病机制，这将为了解自然历史和开发更好的诊断、治疗和临床管理手段提供基础。在NASH CRN的下一阶段，将完成在上一个资助周期中启动的成人和儿科治疗试验，并启动新的治疗试验，包括2a期机制证明和2b期临床试验，以开发安全、有效、简单和廉价的循证治疗方案。成人和儿童NAFLD的纵向队列将被扩大，这将前瞻性地定义疾病的自然史，心血管和代谢危险因素，并将有助于生物标志物的发现和验证，以及非侵入性技术的开发和验证，以评估和识别NASH/NAFLD患者，谁会做出反应，以及疾病进展的速度。自成立以来，VMMC在NASH CRN的临床和转化研究成功中发挥了主导作用。VMMC是PIVENS和FLINT试验的主要入组地点。VMMC目前有5项正在进行的NASH CRN批准的辅助研究，包括AS40，“铁在NAFLD发病机制中的作用”（R01DK087696），该研究对了解铁在NAFLD中的作用做出了重大贡献。VMMC研究人员在国家和国际科学会议上发表了20篇报告，并代表NASH CRN共同撰写了14篇手稿。NASH CRN准备继续其在该领域的重大影响，并直接推进美国国立卫生研究院改善公众健康的使命。

DESCRIPTION (provided by applicant): This application is for the Continuation of the Virginia Mason Medical Center (VMMC) Clinical Site and its Subsites of the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN). Nonalcoholic fatty liver disease (NAFLD) affects one out of every three adults and five children in North America and is a growing public health issue in the United States. NAFLD, and especially nonalcoholic steatohepatitis (NASH), may lead to end-stage liver disease and primary liver cancer, as well as liver-, cardiovascular-, and cancer-related mortality, resulting in major increases in health burdens and costs. The NASH CRN is ideally and uniquely positioned to impact the growing public health significance of NASH that can only be addressed via a large research consortium. The primary objective of the NASH CRN is to perform clinical research on NASH and NAFLD in adults and children. A closely linked and high priority secondary objective is to conduct translational research in NASH and NAFLD focusing on the pathogenesis that will provide the basis for understanding the natural history and developing means of better diagnosis, treatment, and clinical management. In the next phase of the NASH CRN, the adult and pediatric therapeutic trials initiated during the previous funding cycle will be completed, and new therapeutic trials, including phase 2a proof of mechanism and phase 2b clinical trials will be initiated, to develop evidence-based treatment options that are safe, effective, simple, and inexpensive. The longitudinal cohort of adults and children with NAFLD will be extended, which will prospectively define the natural history of the disease, the cardiovascular and metabolic risk factors, and will aid in biomarker discovery and validation, and development and validation of non-invasive techniques to evaluate and identify those with NASH/NAFLD, who will respond, and how quickly the disease is progressing. VMMC has played a leading role in both the clinical and translational research success of the NASH CRN since the inception. VMMC was a leading enrolling site in both the PIVENS and FLINT trials. VMMC currently has 5 ongoing NASH CRN approved ancillary studies, including AS40, "The Role of Iron Pathogenesis of NAFLD" (R01DK087696), which has made major contributions toward understanding the effect of iron in NAFLD. VMMC investigators have contributed 20 presentations at national and international scientific meetings and coauthored 14 manuscripts on behalf of the NASH CRN. The NASH CRN is poised to continue its major impact on the field and directly advance the mission of the National Institutes of Health to improve the health of the public.