This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Determine in nondiabetic adult patients with NASH if improvement in insulin resistance over 96 weeks of treatment with pioglitazone compared to treatment with placebo will result in improvement in NASH disease activity as assessed by a histologic score comprised of steatosis, lobular inflammation and cellular ballooning. Determine in nondiabetic patients with NASH if improvement in oxidative stress status over 96 weeks of treatment with vitamin E compared to treatment with placebo will inprove intrahepatic levels of lipid peroxidations and will result in improvement in NASH disease as assessed by a histologic score comprised of steatostis, lobular inflammation and cellular ballooning. Determine if pioglitazone and vitamin E are equally effective in achieving histologic improvement in diabetic patients with NASH, if levels of proinflammatory cytokines, serum markers of lipid peroxidation, and serum markers for fibrosis will decrease with treatment with pioglitazone and with vitamin E compared to treatment with placebo, and if nondiabetic adult patients with NASH have an impaired quality of life, and these scores will improve as their liver histology improves upon treatment with pioglitazone or vitamin E, compared to treatment with placebo.
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