الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
 |  | from | 143 |  |  |
| | | from | 143 | | |
Abstract
The estimated global prevalence of HCV infection is 3%, corresponding to about 130-210 milion HCV-positive persons worldwide. The highest prevalence (15%-22%) has been reported from Egypt. HCV-infected people serve as a reservoir for transmission of infection to others and are at risk for developing cirrhosis, and HCC.
The treatment of hepatitis C has evolved over the years. Initial studies used IFN monotherapy that produces a SVR in only 5–10% of treated patients. Current treatment is combination therapy consisting of ribavirin and PEG-IFN that increased the SVR rate almost 10 fold up to 54–61%. But unfortunately, this combination regimen has a number of drawbacks. Intolerable side effects necessitate prematurely stopping treatment in about 15% of patients, and dose reductions in another 20–40%. Accordingly, identification of the predictors of response to treatment is a high priority.
A number of viral and host factors associated with response to IFN-based therapy have been identified. Viral factors are limited to viral genotype, HCV RNA titer, and possibly mutations in certain regions of the viral genome. In addition; several host factors are associated with response, such as patient age, sex, ethnicity and cytokine polymorphisms, among these cytokines; IL28B and TNF-a.
Hematologic toxicities of IFN-based combination therapy, such as neutropenia, thrombocytopenia, and anemia can be also predicted by some host genetic polymorphisms such as STAT2 which is involved in IFN signaling pathway.
The aim of this work was to find the effect of Egyptian polymorphism of IL28B and TNF alpha genes on the outcome of chronic HCV infection including; response to combination therapy (peginterferon and ribavirin) as well as the progression into liver cirrhosis and hepatocellular carcinoma. Moreover the effect of STAT2 gene polymorphism on the development of neutropenia induced by IFN therapy was evaluated.