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. Current treatment for chronic hepatitis C (HCV) infection consists of combination therapy with pegylated-interferon (Peg-IFN) and Ribavirin. From previous studies it has been shown that in patients with Hepatitis C, obesity negatively affects treatment response. Our study aims to use the principals of viral kinetics to determine why obese patients do not respond as well as to combination therapy when compared to the non-obese. Viral Kinetics in HCV are determined by serially drawing HCV RNA (viral load) levels and plotting the values on a graph. Early viral kinetics (Phase 1) are determined by the drug's direct inhibition of viral production, whereas late phase kinetics (Phase2) are determined by the ability to clear virus-infected hepatocytes via immune-mediated mechanisms. IN our study, we will be recruiting both obese and non-obese patients who meet our inclusion/exclusion criteria. Each enrolled patient will be admitted to the General Clinical Research Center (GCRC) for 24 hours where they will be administered their firse dose of combination therapy and have serial blood draws. Each blood sample will be sent for quantitative HCV RNA analysis. This early data will be plotted on a graph and used to determine the early viral kinetic parameters. Subsequently, enrolled patients will return at standard appointment intervals and again have HCV RNA levels drawn. This later data will be used to determine the late viral kinetic parameters and each patient's overall response to therapy. The data will be statistically analyzed. The results of our study will potentially change the way we treat obese HCV patients in the future. If obese patients are shown to have poor early viral kinetics when compared to the non-obese, they might benefit from increased doses of combination therapy or alternative routes of administration. If obese patients have poor late viral kinetics, they might benefit from the addition of an immune-modulator to increase the body's ability to clear the virus. Further studies would need to be performed to test these hypotheses.
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