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.
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.
|Hameed, B; Terrault, N A; Gill, R M et al. (2018) Clinical and metabolic effects associated with weight changes and obeticholic acid in non-alcoholic steatohepatitis. Aliment Pharmacol Ther 47:645-656|
|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|
|Ajmera, Veeral; Belt, Patricia; Wilson, Laura A et al. (2018) Among Patients With Nonalcoholic Fatty Liver Disease, Modest Alcohol Use Is Associated With Less Improvement in Histologic Steatosis and Steatohepatitis. Clin Gastroenterol Hepatol 16:1511-1520.e5|
|Dasarathy, Srinivasan; Hatzoglou, Maria (2018) Hyperammonemia and proteostasis in cirrhosis. Curr Opin Clin Nutr Metab Care 21:30-36|
|Lindenmeyer, Christina C; McCullough, Arthur J (2018) The Natural History of Nonalcoholic Fatty Liver Disease-An Evolving View. Clin Liver Dis 22:11-21|
|Rausch, John C; Lavine, Joel E; Chalasani, Naga et al. (2018) Genetic Variants Associated With Obesity and Insulin Resistance in Hispanic Boys With Nonalcoholic Fatty Liver Disease. J Pediatr Gastroenterol Nutr 66:789-796|
|Vuppalanchi, Raj; Siddiqui, Mohammad S; Van Natta, Mark L et al. (2018) Performance characteristics of vibration-controlled transient elastography for evaluation of nonalcoholic fatty liver disease. Hepatology 67:134-144|
|Hajifathalian, Kaveh; Torabi Sagvand, Babak; McCullough, Arthur J (2018) Effect of Alcohol Consumption on Survival in Nonalcoholic Fatty Liver Disease: A National Prospective Cohort Study. Hepatology :|
|Brunt, Elizabeth M; Kleiner, David E; Wilson, Laura A et al. (2018) Improvements in Histologic Features and Diagnosis associated with Improvement in Fibrosis in NASH: Results from the NASH Clinical Research Network Treatment Trials. Hepatology :|
|Harlow, Kathryn E; Africa, Jonathan A; Wells, Alan et al. (2018) Clinically Actionable Hypercholesterolemia and Hypertriglyceridemia in Children with Nonalcoholic Fatty Liver Disease. J Pediatr 198:76-83.e2|
Showing the most recent 10 out of 112 publications