Non Alcoholic Steatohepatitis Clinical Research Network

描述（由申请人提供）：本申请是凯斯西储大学（CWRU）临床站点及其非酒精性脂肪性肝炎临床研究网络（NASH CRN）子站点的延续。非酒精性脂肪性肝病（NAFLD）影响北美近三分之一的成年人和五分之一的儿童，是美国的一个主要公共卫生问题。NAFLD，尤其是非酒精性脂肪性肝炎（NASH），可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负担，这只能通过这个大型研究联盟来解决，并在以前的周期中取得了成功的记录。NASH CRN的主要目标是开展成人和儿童NASH和NAFLD的临床研究。另一个高度优先的目标是开展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，在上一个资助周期中启动的成人和儿科治疗试验将被重新启动

DESCRIPTION (provided by applicant): This application is for the Continuation of the Case Western Reserve University (CWRU) Clinical Site and its Subsites of the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN). Nonalcoholic fatty liver disease (NAFLD) affects nearly a third of adults and a fifth of children in North America and is a major public health issue in the United States. NAFLD, and especially nonalcoholic steatohepatitis (NASH), 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 burden of NASH that can only be addressed through this large research consortium with a demonstrated track record of success in previous cycles. The primary objective of the NASH CRN is to perform clinical research on NASH and NAFLD in adults and children. Another high priority 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. CWRU has played a leading role in both the clinical and translational research success of the NASH CRN since the inception. CWRU was a leading enrolling site in both the PIVENS and FLINT trials. CWRU investigators are uniquely placed in improving understanding of systemic abnormalities including cardiovascular and skeletal muscle dysfunction in NAFLD. The role of sarcopenia and myostatin, a TGF� superfamily member, as a therapeutic target in NASH is a paradigm shifting approach to novel targets for the nearly ubiquitous disease. Given the high recruitment, retention and quality of data from CWRU, and our continued commitment to the success of the collaboration, the NASH CRN is poised to continue its major impact on the field and directly advance the mission of the NIH to improve the health of the public.