الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Egypt has the highest prevalence of HCV, where a recently published EHIS in 2015 showed that 10% of Egyptians between 15 – 59 years of age had been infected with HCV infection. More than 90% of HCV isolates from Egyptian patients are of the GT 4. Until 2015, the standard treatment for HCV infection has been PEG-IFN/RBV, which has limited chance of SVR, intolerable side effects necessitating prematurely stopping treatment in ~ 15% of patients, and dose reductions in another 20–40%. Moreover, the drug regimen is very expensive. For these reasons, the ability to predict treatment outcomes is an important consideration in the management of chronic HCV infection. CD81 is an essential coreceptor for HCV. It is a member of the tetraspanin family.Down-regulation of CD81 has been demonstrated in association with a decrease in the HCV viral load in IFN-α recipients. Several studies have shown that CD81 expression is significant down-regulated during IFNtreatmentin the responders patients. CD137 is a member of the TNFR family, that is expressed on the surface of activated T cells. Itis an important co-stimulatory molecule for induction of virus-specific memory T-cell responses and its ligation enhances T-cell function and promotes survival. Increasing the expression of CD137 has been demonstrated in SVR patients rather than non responder at week 4 and week 12 after the initiation of IFN therapy. Several studies identified genetic variation in IL28B gene as the strongest predictor for control of HCV infection.Results in three possible genotypes: the CC genotype was associated with SVR followed by CT while TT was the least.
To address this issues, the present study examined theIL28B, CD81 and CD137 on CHC Egyptian patients during interferon-based treatment and investigated whether it can affect treatment outcomes.
The present study was conveyed in the period fromOctober 2013 through March 2015 on 44 HCV patients, attending Alexandria Clinical Research Center, Alexandria Medical Research Institute Hospital, Shark Al Madina Hospital and El Kabary Hospital for recieving IFN treatment.
HCV- RNA by real time PCR was performed in all sample before, 3 and 6 months after start of treatment. IL 28B gene polymorphisms by the Multiplex tetra-primer PCR method for rs12979860was performed before treatment. The expression of CD 137 on (CD 4+) and CD 81 on (CD 4+, CD 19+ and CD 56+ ) was performed before, 1, 3 and 6 months after start of treatment.
The main results of the study included:
1. There is no statistical difference between responders and non responders regarding sex (p=0.129), age (p=0.544), body weight (p=0.673) and baseline viral load (p=0.501).
2. There was a statistical significant difference between responders and non responders as regards ALT and AST at baseline, after 3 and 6 months from the start of IFN treatment. There is no statistical difference between responders and non responders and the Hb concentration, WBCs and PLTs countsat baseline, after 3 and 6 months from the start of IFN treatment.
4. There is statistical significant reduction in Hb concentration, WBCs and PLTs counts in different times of measurement for responders and non responders.
5. CD81 expression on different lymphocyte subsets (CD4+ T-helper cells& CD19+ B cells) and NK cells (CD56+) decreased in responders during IFN therapy, while it increased in non-responders.
6. The expression of CD81 expression on different lymphocyte subsets (CD4+ T-helper cells& CD19+ B cells) and NK cells (CD56+) was statistically significant between responders and non responders after 3 and 6 months from the start treatment.
7. CD137 expression on CD4+ T-helper cells increased in responders during IFN therapy, while it decreased in non responders. The expression of CD137 on CD4+was statistically significant between responders and non responders after 1,3 and 6 months from the start treatment.
8. In the present study, expression of CD81 on CD4+,CD19+ and CD56+ (3 months), CD137 on CD4+ % (1 months) and CD137 on CD4+ % (3 months) were statistically significant discriminators of occurrence of response to PEG-IFN/RBV treatment. Pairwise comparisons show no significant differences between expression of them.
9. The frequency of IL28 genotype was the CT genotype (41%) followed by CC (36%) while TT had the least frequency (23%). The response rates were 87.5%, 77.8% and 40% for genotype CC, CT, and TT respectively. Presence at least one copy of the C allele (CC and CT) was associated with 82.4% achieved SVR.
In coclusion:
1. ALT and AST at baseline were statistically significant discriminator of occurrence of response.
2. The expression of CD81 on CD4+,CD19+ and CD56+ (3 months) were statistically significant discriminators of occurrence of response to PEG-IFN/RBV treatment.
3. The expression of CD137 on CD4+ % (1 month) and CD137 on CD4+ % (3 months) were statistically significant discriminators of occurrence of response to PEG-IFN/RBV treatment.
4. There was significant difference between the expression of IL28B between responders and non responders to PEG-IFN/RBV treatment.