الفهرس 
REVIEW OF LITERATUREOnly 14 pages are availabe for public view
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Abstract
Hepatitis C virus (HCV) becomes one of the top curable
chronic diseases worldwide; however, many cases showed
resistance to interferon/Ribavirin combination therapy. Genetic
polymorphism is the major cause of relapse after therapy. To
determine whether HCV core substitution and IL-28B (rs8099917
and rs12979860) play a role in the response to INF/RBV antiviral
therapy; 50 HCV chronically infected patients who initiated
treatment with Pegylated INF plus ribavirin (INF/RBV) for 48
weeks were tested for genetic polymorphism in IL-28B rs8099917
and rs12979860 to determine their effects on virological response
of the INF/RBV regimen.
The response to treatment was assessed at 12 weeks after
therapy to determine the achievement of sustained viral response
(SVR), patient was considered as a responder if he achieved
reduction by two folds of the HCV_RNA viral load; otherwise, it
was considered as non-responder. Also patients were assessed at
24 weeks after therapy to evaluate their late response (LVR) to
INF/RBV. In addition; liver function tests were evaluated to
determine hepatic status and severity of infection.
In the current study, among IL28b (rs8099917 G/T)
genotypes TT genotype was the most predominant genotype
among the HCV genotype 4 infected patients (64%) followed by
GT genotype (32%), however GG genotype were minor group (4%). TT and GT genotypes showed high tendency for response to
INF/RBV at 12 weeks (p=0.04). Although; the majority of patients
who had achieved LVR were of TT genotype (66%) followed by
GT genotype (50%), no significant association was observed
between IL28b (rs8099917 G/T) genotype and LVR to INF/RBV
(p=0.09). However 100% of GG genotype didn‟t response to
therapy. HCV patients who were negative for G allele “TT
genotype” showed a significantly higher tendency to respond at 12
weeks compared to G positive group [p=0.02]. On contrary, no
significant associations were detected between the positivity of T
allele and either SVR or LVR (p>0.05). Likewise, significance
could not reached between positivity of G allele and late viral
response at 24 weeks (p>0.05).
Considering the distribution of rs12979860 C/T genotypes
among HCV-4 infected patients as well their response to INF/RBV
at 12 weeks; 58% of patients were of TT genotype, followed by
28% of CC, while CT genotypes accounts the least percentage
(14%). No significant association was observed between the
genotype and response to therapy at 12 weeks (p=0.06). Although;
the majority (86%) of CT genotype patients didn‟t response to
therapy at 24 weeks, the majority of CC (86%) genotype respond
to INF/RBV and TT genotype showed equal distribution among
responders and non-responders. A high significant association was
observed between the positivity of T allele and LVR to INF/RBV.
On contrary, no significant associations were detected between the positivity of C allele and either SVR or LVR (p>0.05). Likewise,
significance could not reached between positivity of T allele and
SVR (p>0.05). However; no significant difference was detected
between different genotypes of each studied polymorphism and the
severity of infection.
In conclusion; IL28B polymorphism rs12979860 was found
to be excellent biomarkers for prediction of therapeutic response to
PEGINF/RBV therapies in Egyptians with chronic HCV genotype4.