Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN)

非酒精性脂肪性肝炎（NASH）的流行将不会受到限制，除非合作努力， 识别、预防和治疗促使人类NASH发病和进展的因素。解决 面对这一挑战，NIDDK建立了NASH临床研究网络（NASH CRN），这是一个致力于 促进与成人和儿童NASH相关的临床和转化科学。CRN广泛 被认为是NASH领域的领导者，因为它开发了世界上最大的，最具特色的， 对成人和儿童NASH患者进行了最长时间的前瞻性随访， NASH受试者的前瞻性随机安慰剂对照试验（RCT）。展望未来，CRN将 利用这项工作产生的信息来推进诊断测试、疾病生物标志物的开发， 进展，安全，成本有效的NASH治疗。这份竞争性的续约申请来自 杜克/卢里儿童医院网站详细介绍了我们网站的工作计划，我们将在未来几年内完成 作为CRN成员的资金周期。除了我们的详细方法，以确保所有CRN活动的成功 (Aim 1），我们进一步提出了一个新的多中心随机对照试验，评估阿托伐他汀作为一种通用的“再用途”药物， NASH的治疗（目标2）和相关的转化科学，以提供有关如何 他汀类药物影响NASH（目标3）。后两个项目是我们早期CRN研究的自然延伸， 证明了Hedgehog（一种脂质调节的信号通路）在决定肿瘤进展中的重要性。 NASH和NASH相关的纤维化。这些目标的实现将进一步推进NASH CRN任务， 描述NASH的自然史，并确定安全和具有成本效益的预防和治疗NASH的新干预措施， 治疗NASH。

The epidemic of nonalcoholic steatohepatitis (NASH) will not be constrained without collaborative efforts to identify, prevent, and treat the factors that drive NASH pathogenesis and progression in humans. To address this challenge the NIDDK established the NASH Clinical Research Network (NASH CRN), a consortium devoted to advancing clinical and translational science pertinent to adult and pediatric NASH. The CRN is widely considered to be a leader in the NASH field because it has developed the world’s largest, best-characterized, and longest prospectively-followed cohort of adult and pediatric NASH patients and done several definitive prospective randomized placebo-controlled trials (RCTs) in NASH subjects. Moving forward, the CRN will leverage information generated by this work to advance development of diagnostic tests, biomarkers of disease progression, and safe, cost-effective treatments for NASH. This competitive renewal application from the Duke/Lurie Children’s Hospital site details our site’s plans for the work that we will accomplish during the next funding cycle as CRN members. In addition to our detailed approach to ensure success of all CRN activities (Aim 1), we further propose a new multi-center RCT evaluating atorvastatin as a generic “repurposed” drug for the treatment of NASH (Aim 2) and related translational science to provide mechanistic information about how statins impact NASH (Aim 3). The latter two projects are natural extensions of our earlier CRN studies which demonstrated the importance of Hedgehog, a lipid-regulated signaling pathway, in determining progression of NASH and NASH-related fibrosis. Accomplishment of these Aims will advance NASH CRN missions by further delineating NASH natural history and identifying novel interventions that safely and cost-effectively prevent and treat NASH.