Non-alcoholic steatohepatitis (NASH) is a relatively common disorder characterized by the presence of fat in the liver accompanied by inflammatory changes (infiltration with polymorphonuclear cells, presence of Mallory bodies, hepatocyte necrosis, and in some cases fibrosis or cirrhosis). Earlier studies have recognized a relationship of NASH to obesity and diabetes, as well as to the toxicity of several drugs. However, virtually nothing is known of it pathophysiology, and thus rational therapy, aide from the treatment of obesity and diabetes, and discontinuation of offending drugs, is not yet possible. We propose that NASH is a final pathological response to a number of insults to the liver that result in elevated liver free fatty acid levels. This leads to triglyceride accumulation, which in turn renders the liver in some individuals more sensitive to lipid peroxidation or to endotoxinemia (or other activators of cytokine cascades). We will gain information about the pathophysiology of this disease by comparing liver biopsy-proven NASH patients with controls matched for age, gender, race, and presence of diabetes for metabolic fuel usage, insulin sensitivity, activation of cytokine pathways, lipid peroxidation, and body fat distribution. The results of this study should point to important metabolic differences between controls and NASH patients, suggesting risk factors that can be modified and leading to trials of therapy aimed at correcting the abnormalities defined.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Small Research Grants (R03)
Project #
5R03DK056012-02
Application #
6177663
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Everhart, James
Project Start
1999-09-30
Project End
2002-08-31
Budget Start
2000-09-01
Budget End
2002-08-31
Support Year
2
Fiscal Year
2000
Total Cost
$71,162
Indirect Cost
Name
Indiana University-Purdue University at Indianapolis
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
603007902
City
Indianapolis
State
IN
Country
United States
Zip Code
46202
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