This application is for the Continuation of the Case Western Reserve University (CWRU) Clinical Site and its Subsites of the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN). Nonalcoholic fatty liver disease (NAFLD) affects nearly a third of adults and a fifth of children in North America and is a major public health issue in the United States. NAFLD, and especially nonalcoholic steatohepatitis (NASH), 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 burden of NASH that can only be addressed through this large research consortium with a demonstrated track record of success in previous cycles. The primary objective of the NASH CRN is to perform clinical research on NASH and NAFLD in adults and children. Another high priority 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. CWRU has played a leading role in both the clinical and translational research success of the NASH CRN since the inception. CWRU was a leading enrolling site in both the PIVENS and FLINT trials. CWRU investigators are uniquely placed in improving understanding of systemic abnormalities including cardiovascular and skeletal muscle dysfunction in NAFLD. The role of sarcopenia and myostatin, a TGF? superfamily member, as a therapeutic target in NASH is a paradigm shifting approach to novel targets for the nearly ubiquitous disease. Given the high recruitment, retention and quality of data from CWRU, and our continued commitment to the success of the collaboration, the NASH CRN is poised to continue its major impact on the field and directly advance the mission of the NIH to improve the health of the public.

Public Health Relevance

Nonalcoholic fatty liver disease (NAFLD) affects nearly a third of adults and a fifth of children in North America. The spectrum of NAFLD ranges from fatty liver to nonalcoholic steatohepatitis (NASH) and NASH cirrhosis. NAFLD, especially NASH, is associated with increased liver-, cardiovascular-, and cancer-related mortality. The goal of the NASH CRN is to transform scientific discoveries from laboratory, clinical, and epidemiological studies into clinical applications to reduce the burden of the disease.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project--Cooperative Agreements (U01)
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Special Emphasis Panel (ZDK1-GRB-7 (M2))
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Doo, Edward
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Cleveland Clinic Lerner
Internal Medicine/Medicine
Schools of Medicine
United States
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Dasarathy, Srinivasan; Dasarathy, Jaividhya; Khiyami, Amer et al. (2015) Double-blind randomized placebo-controlled clinical trial of omega 3 fatty acids for the treatment of diabetic patients with nonalcoholic steatohepatitis. J Clin Gastroenterol 49:137-44
Mehta, Minesh; Slaughter, Crystal; Xanthakos, Stavra A et al. (2014) High prevalence of hepatitis B non-immunity in paediatric non-alcoholic fatty liver disease patients. Dig Liver Dis 46:760-1
Molleston, Jean P; Schwimmer, Jeffrey B; Yates, Katherine P et al. (2014) Histological abnormalities in children with nonalcoholic fatty liver disease and normal or mildly elevated alanine aminotransferase levels. J Pediatr 164:707-713.e3
Chen, Qing-Rong; Braun, Rosemary; Hu, Ying et al. (2013) Multi-SNP analysis of GWAS data identifies pathways associated with nonalcoholic fatty liver disease. PLoS One 8:e65982
Glass, Cathy; Hipskind, Peggy; Tsien, Cynthia et al. (2013) Sarcopenia and a physiologically low respiratory quotient in patients with cirrhosis: a prospective controlled study. J Appl Physiol (1985) 114:559-65
Sourianarayanane, Achuthan; O'Shea, Robert S; Barnes, David S et al. (2013) High prevalence of normal serum albumin in NASH patients with ascites: a retrospective analysis. Clin Res Hepatol Gastroenterol 37:246-53
Vos, Miriam B; Colvin, Ryan; Belt, Patricia et al. (2012) Correlation of vitamin E, uric acid, and diet composition with histologic features of pediatric NAFLD. J Pediatr Gastroenterol Nutr 54:90-6
Guerrerio, Anthony L; Colvin, Ryan M; Schwartz, Amy K et al. (2012) Choline intake in a large cohort of patients with nonalcoholic fatty liver disease. Am J Clin Nutr 95:892-900
Dunn, Winston; Sanyal, Arun J; Brunt, Elizabeth M et al. (2012) Modest alcohol consumption is associated with decreased prevalence of steatohepatitis in patients with non-alcoholic fatty liver disease (NAFLD). J Hepatol 57:384-91
Bambha, Kiran; Belt, Patricia; Abraham, Maria et al. (2012) Ethnicity and nonalcoholic fatty liver disease. Hepatology 55:769-80

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