THE RELATIONSHIP OF HEPATIC STEATOSIS TO ENDOTHELIAL DYSFUNCTION IN PATIENTS

Virginia Commonwealth University, Richmond VA

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Abstract

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. In HIV infected subjects, the presence of NAFLD is associated with increased evidence of vascular injury and cardiovascular disease due to the systemic activation of lipoxygenase which in turn causes endothelial dysfunction and promotes atherosclerosis. The specific aims: 1. To define the impact of hepatic steatosis on the severity of endothelial injury and macrovascular cardiovascular status in subjects with HIV infection. 2. To assess, through lipidomic analysis, the relationship between endothelial dysfunction and hepatic steatosis in patients with HIV. In this pilot study, 10 HIV patients who had previously undergone liver biopsy for liver disease who have steatosis (>5%) and 10 matched by age ([unreadable] 5 yrs), gender, and race without steatosis (<5%) will be selected from the data base (VCU IRB#6033). All subjects will meet inclusion/exclusion criteria. At baseline demographics, comorbid conditions (diabetes, hypertension, hepatitis B or C), antiretroviral therapy history, body composition (using anthropometrics and DEXA), presence of the metabolic syndrome (using ATPIII criteria), alcohol use (assessed by AUDIT), THC use, smoking history, and laboratories for CBC, CD4/CD8, HIV RNA, and serum chemistries (basic metabolic and hepatic panel) and fasting lipids. The primary endpoint is increased cIMT. Subjects will have endothelial dysfunction assessed by finger arterial pulse wave amplitude (EndoPAT) and Framingham score will be calculated for future cardiovascular risk. MR spectroscopy will be performed to assess for hepatic steatosis. Serum/plasma will be assessed for insulin resistance (HOMA-IR), inflammatory biomarkers, and lipidomic analysis.