This application is for the Continuation of the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) - Data Coordinating Center. 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 larger 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. Duke University will provide the NASH CRN with expert basic science and clinical-translational expertise in NAFLD, the ability to readily recruit adults and children into prospective clinical trials, and perform ancillary studies to fill existin gaps in knowledge. Duke University and our pediatric sites, Ann &Robert H. Lurie Children's Hospital/JHU, are eager to continue our collaboration with NIDDK program staff, the Data Coordinating Center, private sector partner and other clinical centers to complete the important research objective 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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
2U01DK061713-13
Application #
8768952
Study Section
Special Emphasis Panel (ZDK1)
Program Officer
Doo, Edward
Project Start
2002-05-01
Project End
2019-06-30
Budget Start
2014-08-01
Budget End
2015-06-30
Support Year
13
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Duke University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
Durham
State
NC
Country
United States
Zip Code
27705
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Africa, Jonathan A; Behling, Cynthia A; Brunt, Elizabeth M et al. (2018) In Children With Nonalcoholic Fatty Liver Disease, Zone 1 Steatosis Is Associated With Advanced Fibrosis. Clin Gastroenterol Hepatol 16:438-446.e1
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Yates, Katherine P; Deppe, Ross; Comerford, Megan et al. (2017) Serum high mobility group box 1 protein levels are not associated with either histological severity or treatment response in children and adults with nonalcoholic fatty liver disease. PLoS One 12:e0185813
Middleton, Michael S; Heba, Elhamy R; Hooker, Catherine A et al. (2017) Agreement Between Magnetic Resonance Imaging Proton Density Fat Fraction Measurements and Pathologist-Assigned Steatosis Grades of Liver Biopsies From Adults With Nonalcoholic Steatohepatitis. Gastroenterology 153:753-761

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