This application is for the Continuation of the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) - IU Clinical 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 large 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. IU Clinical Center will actively participate in the (a) successful completion of the ongoing studies, (b) successful launching of new therapeutic trials and (c) development of new ancillary and publication proposals. In addition, IU Clinical Center investigators will actively participate in various committees including the Steering Committee, Ancillary Studies Committee, Genetics Subcommittee, Pediatrics Committee, Pathology Committee and Imaging Committee. IU Clinical Center is eager to continue its collaboration with other clinical centers, data coordinating center, NIDDK program staff, and private sector partners to complete these very important research objectives. 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 #
2U01DK061737-13
Application #
8772596
Study Section
Special Emphasis Panel (ZDK1)
Program Officer
Doo, Edward
Project Start
2002-05-20
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
Indiana University-Purdue University at Indianapolis
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
Indianapolis
State
IN
Country
United States
Zip Code
46202
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
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
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
Corey, Kathleen E; Vuppalanchi, Raj; Vos, Miriam et al. (2015) Improvement in liver histology is associated with reduction in dyslipidemia in children with nonalcoholic fatty liver disease. J Pediatr Gastroenterol Nutr 60:360-7
Bazick, Jessica; Donithan, Michele; Neuschwander-Tetri, Brent A et al. (2015) Clinical Model for NASH and Advanced Fibrosis in Adult Patients With Diabetes and NAFLD: Guidelines for Referral in NAFLD. Diabetes Care 38:1347-55

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