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.
Nonalcoholic fatty liver disease (NAFLD) affects one in three adults and one in five children in North America. NAFLD ranges from nonalcoholic fatty liver to nonalcoholic steatohepatitis (NASH). NAFLD, especially NASH, is associated with increased liver-, cardiovascular-, and cancer-related mortality. The NASH CRN aims to transform scientific discoveries from laboratory, clinical, and population studies into clinical applications to reduce the incidence and burden of adverse outcomes due to NAFLD and NASH.
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