BACKGROUND: In the United States, chronic hepatitis C virus (HCV) infection afflicts approximately 3.2 million persons and is the leading indication of liver transplantation. Therapies for chronic HCV are not completely effective and African Americans are significantly less responsive to therapy than Caucasian Americans. Studies suggest that lipoproteins and cholesterol metabolism play a role in biological mechanisms of the HCV life cycle. This dissertation characterizes the serum lipid profile in a cohort with genotype 1 chronic HCV infection, the predominant HCV genotype in the United States. STUDY POPULATION: Participants for this study were from the Virahep-C study, a prospective study of resistance to antiviral therapy involving 401 treatment naïve people with chronic hepatitis C (genotype 1) infection who underwent combination pegylated interferon alfa-2a + ribavirin therapy for up to 48 weeks. Included in this dissertation analysis were 330 participants who had serum lipid profile data before starting therapy. RESULTS: Before treatment, HCV viral level was directly associated with triglyceride levels, liver fat was directly and inversely related to triglycerides and high density lipoprotein cholesterol, respectively, and severe fibrosis was associated with lower of total and high density lipoprotein cholesterol levels. Over the course of therapy, all lipid profile measures changed during 6 months of treatment, and post-treatment, changes were limited to 6 month virological responders. For some lipid profile measures, changes during 6 months of treatment differed by race and were related to the amount of interferon taken. Lastly, components of the lipid profile were significant predictors of sustained virological response in univariable and multivariable analyses. CONCLUSIONS: This dissertation highlights the importance of the lipid profile in relation to aspects of liver disease, potential mechanisms of HCV eradication attributed to antiviral therapy, and virological response to therapy. The findings are of public health significance as they may highlight opportunities for new therapeutic targets and intervention studies to improve virological response, as well as elucidate factors involved in the racial disparity in treatment efficacy.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-07302008-160609 |
| Date | 28 September 2008 |
| Creators | Ramcharran, Darmendra |
| Contributors | Hari S Conjeevaram, MD, MS, Steven H Belle, PhD, MScHyg, Leland J Yee, PhD, MPH, Abdus S Wahed, PhD, Rhobert Evans, PhD |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-07302008-160609/ |
| Rights | restricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Pittsburgh or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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