Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are important causes of chronic liver disease in the United States. The NASH Clinical Research Network (NASH CRN) was established in 2002 to conduct research related to its clinical features, risk factors, pathogenesis, natural history and treatment in children and adults. The initial funding period of the NASH CRN has been very productive in establishing and conducting network-wide protocols and numerous ancillary and pilot studies. Encouraged by its success, the NIDDK has issued RFA-DK-08-505 whose objective is to continue the NASH CRN for additional five years. The objectives of the NASH CRN during the next funding period are (a) to successfully complete three network-wide studies initiated during the initial funding period. They are an observational longitudinal study of NAFLD in adults and children (NAFLD Database study, n=1,215), a randomized double blind controlled therapeutic study of NASH in non-diabetic adults (PIVENS, n=247), and a randomized double blind controlled therapeutic study of NAFLD in children (TONIC, n=173). The NAFLD Database study may be amended to meet additional goals during the next funding period. These modifications may include extending the length of follow-up of those enrolled, consideration of a follow-up liver biopsy in a subset of patients without cirrhosis for better assessment of histological natural history and enrolling carefully chosen controls without NAFLD;(b) to successfully complete a large of ancillary studies and pilot studies that have been begun during the initial funding period;(c) to conduct additional therapeutic studies in adults and children with NASH as options currently available to treat NASH are quite limited. Subsets of patients requiring immediate attention include (but not limited) to those with diabetes or cirrhosis and (d) to initiate and complete additional ancillary studies based on extensive clinical material and biosamples collected thus far. These studies may focus on (but are not limited to) natural history of NAFLD and NASH in children and adults, non-invasive assessment of disease severity (e.g., proteomics, lipodimics, clinical prediction rules) and disease pathogenesis (cytokine analyses, genome-wide association studies, tissue proteomics). Two new ancillary studies proposed by the UCSF Clinical Center aim to: a) Develop a non-invasive alternative to liver biopsy for the evaluation and monitoring of hepatic fibrosis in NAFLD CRN patients using novel MRI imaging and MR spectroscopic techniques, and b) Elucidate the impact of NAFLD on cardiac lipotoxicity, cardiac energetics, and myocardial function in NASH CRN patients using cardiac MRI and proton mass spectroscopy.

Public Health Relevance

(provided by the applicant): NAFLD and NASH are important health problems and their incidence is expected to increase. During the initial funding period, the NASH CRN has made important contributions to the field of NAFLD and NASH, however there remain numerous unanswered questions. During the next funding period, the CRN will continue to investigate risk factors, clinical aspects, natural history and optimal treatment for NASH and associated conditions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
3U01DK061738-12S1
Application #
8701112
Study Section
Special Emphasis Panel (ZDK1-GRB-7 (M1))
Program Officer
Doo, Edward
Project Start
2002-06-15
Project End
2014-04-30
Budget Start
2013-05-01
Budget End
2014-04-30
Support Year
12
Fiscal Year
2013
Total Cost
$78,761
Indirect Cost
$7,407
Name
University of California San Francisco
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
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
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
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
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
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
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

Showing the most recent 10 out of 69 publications