Investigators at the University of California, San Diego propose their continued inclusion as a Clinical Center within the """"""""Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN)"""""""". NASH is the most prevalent liver disease in children and one of the most common causes of chronic liver disease in adults. NASH is associated with cardiovascular disease risk factors such as type 2 diabetes, hypertension, dyslipidemia and obesity. The Network's broad, long-term objectives are to advance understanding of the pathogenesis, natural history, genetics, histopathology and treatment for NASH. The NASH CRN currently is conducting 2 multi-center, double-blind, randomized, placebo-controlled clinical trials which require completion in the renewal period, one In children 8-17 years inclusive and the other in adults 18 years and over. The pediatric study called """"""""TONIC"""""""", has 173 subjects enrolled for a 2-year treatment, assessing safety and efficacy of metformin or Vitamin E versus placebo. The adult study called """"""""PIVENS"""""""", has 247 subjects enrolled for 2-years of treatment to assess pioglitazone or Vitamin E versus placebo. Additionally, there is a genetics study called """"""""GOALS"""""""", which requires many more children and their parents to enroll in order to identify candidate genes associated with NASH, and an ongoing Database study with 1262 current subjects intended to assess the natural history of NASH. The Database also will be invaluable for evaluating life-style factors in NASH and evaluating noninvasive biomarkers and imaging for diagnosis and progression. In this renewal we aim to expand the database with under-represented and important biopsy-proven sub-populations such as children (particularly girls), Hispanics, blacks and those with cirrhosis to better understand the role of age, gender, ethnicity, race, genetics and lifestyle in the development of NASH and Its co-morbidities.
We aim to Identify appropriately matched control populations without NAFLD to permit comparisons to those with NAFLD. We propose the conduct of another randomized placebo-controlled clinical trial to assess other treatment options for children with NASH, and we will complete, analyze and report on the treatment studies from the last grant period now coming to fruition.
(provided by the applicant): This national multi-center Clinical Research Network is studying the genetic and environmental reasons why certain people develop fat accumulation of the liver with oft concomitant hepatic inflammation and scarring. Further knowledge about this common and increasingly prevalent disease is needed for prevention, non-invasive diagnosis, understanding of natural history and evaluation of safe and effective therapy.
|Yu, N Y; Wolfson, T; Middleton, M S et al. (2017) Bone marrow fat content is correlated with hepatic fat content in paediatric non-alcoholic fatty liver disease. Clin Radiol 72:425.e9-425.e14|
|Schwimmer, Jeffrey B; Behling, Cynthia; Angeles, Jorge Eduardo et al. (2017) Magnetic resonance elastography measured shear stiffness as a biomarker of fibrosis in pediatric nonalcoholic fatty liver disease. Hepatology 66:1474-1485|
|Africa, Jonathan A; Behling, Cynthia A; Brunt, Elizabeth M et al. (2017) In Children With Nonalcoholic Fatty Liver Disease, Zone 1 Steatosis Is Associated With Advanced Fibrosis. Clin Gastroenterol Hepatol :|
|Wattacheril, Julia; Lavine, Joel E; Chalasani, Naga P et al. (2017) Genome-Wide Associations Related to Hepatic Histology in Nonalcoholic Fatty Liver Disease in Hispanic Boys. J Pediatr 190:100-107.e2|
|Perito, Emily R; Ajmera, Veeral; Bass, Nathan M et al. (2017) Association Between Cytokines and Liver Histology in Children with Nonalcoholic Fatty Liver Disease. Hepatol Commun 1:609-622|
|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|
|Yang, Ju Dong; Abdelmalek, Manal F; Guy, Cynthia D et al. (2017) Patient Sex, Reproductive Status, and Synthetic Hormone Use Associate With Histologic Severity of Nonalcoholic Steatohepatitis. Clin Gastroenterol Hepatol 15:127-131.e2|
|Vos, Miriam B; Abrams, Stephanie H; Barlow, Sarah E et al. (2017) NASPGHAN Clinical Practice Guideline for the Diagnosis and Treatment of Nonalcoholic Fatty Liver Disease in Children: Recommendations from the Expert Committee on NAFLD (ECON) and the North American Society of Pediatric Gastroenterology, Hepatology and Nu J Pediatr Gastroenterol Nutr 64:319-334|
|Ajmera, Veeral; Perito, Emily R; Bass, Nathan M et al. (2017) Novel plasma biomarkers associated with liver disease severity in adults with nonalcoholic fatty liver disease. Hepatology 65:65-77|
|Newton, Kimberly P; Feldman, Haruna S; Chambers, Christina D et al. (2017) Low and High Birth Weights Are Risk Factors for Nonalcoholic Fatty Liver Disease in Children. J Pediatr 187:141-146.e1|
Showing the most recent 10 out of 90 publications