Clinical Research Network in Nonalcoholic Steatohepatitis

描述(由申请人提供)：本申请是弗吉尼亚梅森医学中心(VMMC)临床网站及其非酒精性脂肪性肝炎临床研究网络(NASH CRN)的子网站的延续。非酒精性脂肪性肝病(NAFLD)在北美每三个成年人和五个儿童中就有一个受到影响，在美国是一个日益严重的公共卫生问题。非酒精性脂肪肝，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，以及与肝脏、心血管和癌症相关的死亡，导致医疗负担和成本的大幅增加。NASH CRN是影响NASH日益增长的公共卫生意义的理想和独特的定位，只能通过大型研究联盟来解决。NASH CRN的主要目标是在成人和儿童中进行NASH和NAFLD的临床研究。一个密切联系和高度优先的次要目标是在NASH和NAFLD中进行转译研究，重点是发病机制，这将为了解NASH和NAFLD的自然历史和开发更好的诊断、治疗和临床管理方法提供基础。在NASH CRN的下一阶段，将完成在前一个资金周期启动的成人和儿童治疗试验，并将启动新的治疗试验，包括2a阶段机制证明和2b阶段临床试验，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患者的纵向队列将扩大，这将前瞻性地定义疾病的自然病史、心血管和代谢风险因素，并将有助于生物标记物的发现和验证，以及非侵入性技术的开发和验证，以评估和识别NASH/NAFLD患者、谁将做出反应以及疾病进展有多快。自NASH CRN成立以来，VMMC在NASH CRN的临床和翻译研究成功方面发挥了主导作用。VMMC在皮文斯和弗林特试验中都是领先的注册网站。VMMC目前有5项正在进行的NASH CRN批准的辅助研究，其中包括AS40《NAFLD中铁的发病机制的作用》(R01DK087696)，该研究为理解铁在NAFLD中的作用做出了重大贡献。VMMC调查人员在国家和国际科学会议上提交了20份报告，并代表NASH CRN共同撰写了14份手稿。NASH CRN准备继续其在该领域的主要影响，并直接推动国家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.