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. Insulin resistance and oxidative stress are considered to be the two most important mechanisms in the pathogenesis of NASH. The investigators hypothesize that measures to improve insulin resistance or oxidative stress will lead to improvement in hepatic histology in nondiabetic adults with biopsy proven NASH. In nondiabetic adult patients with NASH, 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. In nondiabetic adult patients with NASH, improvement in oxidative stress status over 96 weeks of treatment with vitamin E, compared to treatment with placebo, will improve intrahepatic levels of lipid peroxidation and will result in improvement in NASH disease activity as assessed by a histologic score of steatosis, lobular inflammation, and cellular ballooning. The general aim of this study is to evaluate whether 96 weeks of treatment with either pioglitazone or vitamin E lowers NASH activity as determined from hepatic histology in nondiabetic adults with NASH
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