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.
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.
|Klair, Jagpal Singh; Yang, Ju Dong; Abdelmalek, Manal F et al. (2016) A longer duration of estrogen deficiency increases fibrosis risk among postmenopausal women with nonalcoholic fatty liver disease. Hepatology 64:85-91|
|Nelson, J E; Handa, P; Aouizerat, B et al. (2016) Increased parenchymal damage and steatohepatitis in Caucasian non-alcoholic fatty liver disease patients with common IL1B and IL6 polymorphisms. Aliment Pharmacol Ther 44:1253-1264|
|Schwimmer, Jeffrey B; Lavine, Joel E; Wilson, Laura A et al. (2016) In Children With Nonalcoholic Fatty Liver Disease, Cysteamine Bitartrate Delayed Release Improves Liver Enzymes but Does Not Reduce Disease Activity Scores. Gastroenterology 151:1141-1154.e9|
|Kanwar, Pushpjeet; Nelson, James E; Yates, Katherine et al. (2016) Association between metabolic syndrome and liver histology among NAFLD patients without diabetes. BMJ Open Gastroenterol 3:e000114|
|Michelotti, Gregory; Jiang, Xiaoyin; Sosa, Julie Ann et al. (2015) LGR5 is associated with tumor aggressiveness in papillary thyroid cancer. Oncotarget 6:34549-60|
|Corey, K E; Vuppalanchi, R; Wilson, L A et al. (2015) NASH resolution is associated with improvements in HDL and triglyceride levels but not improvement in LDL or non-HDL-C levels. Aliment Pharmacol Ther 41:301-9|
|Neuschwander-Tetri, Brent A; Loomba, Rohit; Sanyal, Arun J et al. (2015) Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial. Lancet 385:956-65|
|Guy, Cynthia D; Suzuki, Ayako; Abdelmalek, Manal F et al. (2015) Treatment response in the PIVENS trial is associated with decreased Hedgehog pathway activity. Hepatology 61:98-107|
|Abdelmalek, Manal F; Day, Chris (2015) Sugar sweetened beverages and fatty liver disease: Rising concern and call to action. J Hepatol 63:306-8|
|Hourigan, Suchitra K; Abrams, Stephanie; Yates, Katherine et al. (2015) Relation between vitamin D status and nonalcoholic fatty liver disease in children. J Pediatr Gastroenterol Nutr 60:396-404|
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