Thesis (Ph.D.) - Cairo University - Faculty of Science - Department of Biochemistry

Hepatitis C virus (HCV) is the cause of a significant proportion of cases of chronic liver disease, Hepatocellular carcinoma (HCC) and deaths from liver disease. Egypt has the highest prevalence of HCV worldwide (15%) and the highest prevalence of HCV genotype 4, which is responsible for almost 90% of infections.DNA methylation plays a critical role in the control of important cellular processes and potentiates the progression of HCV related liver disease and affects its response to therapy. Our study aims to show the impact of promoter methylation (PM) of some genes {APC )Adenomatous polyposis coli(, P14ARF, P73, DAPK( Death-associated protein kinase), RASSF1A(Ras-Association Domain Family 1) and O6MGMT(methylguanine-DNA methyltransferase)} on the antiviral response to antiviral therapy and its relation to the presence of fibrosis in HCV-4 infected patients from Egypt. Clinical, laboratory and histopathological data of 53 HCV-4 infected patients who were subjected to combined antiviral therapy were collected; patients were classified according to their response to treatment into: Group I: This group included 24 CH patients non-responded to IFN treatment after 27 weeks positive for HCV infection by RT-PCR. Group II: This group included 29 CH patients responded to IFN treatment after 72 weeks negative for HCV infection by RT-PCR. The main results of this study are the PM of some Tumor Suppressor genes increases in chronic active HCV-4.However, only O6MGMT gene can be used as a predictor of antiviral response and RASSF1A gene as a marker of mild fibrosis grade in the studied patients

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