Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN)

如果没有合作努力，非酒精性脂肪性肝炎(NASH)的流行将不会受到限制 识别、预防和治疗推动人类NASH发病和进展的因素。致信地址 在这次挑战中，NIDDK建立了NASH临床研究网络(NASH CRN)，该联盟致力于 促进与成人和儿童NASH相关的临床和翻译科学。CRN的应用非常广泛 被认为是纳什领域的领导者，因为它开发了世界上最大、最具特色的 对成人和儿童NASH患者进行了最长的前瞻性跟踪队列，并进行了几项决定性的 NASH受试者的前瞻性随机安慰剂对照试验。展望未来，CRN将 利用这项工作产生的信息来推动诊断测试、疾病生物标记物的开发 进展，以及安全、成本效益高的NASH治疗。此竞争性续订申请来自 杜克/卢里儿童医院网站详细说明了我们网站在下一年将完成的工作计划 作为CRN成员的资金周期。除了我们确保所有CRN活动成功的详细方法之外 (目标1)，我们进一步提出了一种新的多中心随机对照试验，评估阿托伐他汀作为一种用于治疗的仿制药 NASH的治疗(目标2)和相关的翻译科学，以提供关于如何 他汀类药物影响纳什(目标3)。后两个项目是我们早先的CRN研究的自然延伸 证明了Hedgehog，一个脂质调节的信号通路，在决定糖尿病进展过程中的重要性 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 描绘纳什自然历史并确定安全和经济高效地预防和 治疗纳什。

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.