الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 184 |  |  |
| | | from | 184 | | |
Abstract
Infection with hepatitis C virus (HCV) affects millions of people
worldwide and leads to chronic liver disease. HCV infection may often
progress to cirrhosis and hepatocellular carcinoma.
The standard of care (SOC) treatment of chronic HCV infection
consists of (pegylated) interferon-alpha and oral ribavirin but unfortunately
it does not produce SVR in all treated patients, expensive and associated
with significant side effects.
To avoid these side effects in patients who will not be helped by the
treatment, as well as to reduce the substantial cost of (pegylated)
interferon-alpha and ribavirin treatment, it would be useful to be able to
predict an individual’s response before or early in treatment.
Vitamin D is a potent immunomodulator that favors innate immunity
and cell differentiation. Vitamin D deficiency is very common in patients
with CHC. This deficiency may reduce the rate of success of interferon
plus ribavirin combined antiviral therapy. Genetic polymorphisms
affecting the vitamin D receptor gene have been implicated in several
immune disorders
We aimed at our study to detect the effect of SNPs of vitamin D
receptor (Fok1 rs2228570 T/C and Apa1 rs7975232C/A) and (interleukin-
28B rs12979860 C/T) polymorphisms on sustained virological response to
interferon/ribavirin based therapy in Egyptian patients with chronic
Hepatitis C.
This study was conducted on 80 patients with chronic HCV who
received pegylated interferon & ribavirin after taking written informed
consent from the patients and 20 healthy control persons.
The following were done: DNA extraction from whole blood, PCR
for gene amplification, agarose gel electrophoresis and quantitation of
vitamin D level by ELISA.
We found a significant difference regarding sex in relation to response
with higher percent of response among males being 53.6 versus 22.7
among females with p value=0.007
Moreover, we found a significant difference between responders and
non responders to interferon/ribavirin based therapy of chronic hepatitis C
patients before treatment as regards alkaline phosphatase, viral load,
random blood sugar and AFP which were significantly higher in nonresponders
group than in SVR group with (P value <0.001, 0.038, 0.026
and <0.001 respectively). There was significant difference regarding
vitamin D level with higher frequency of patients with vitamin D level less
than 20ng/ml among non-responders in comparison to SVR group with p
value<0.001
Also, we found a significant difference regarding IL28B rs12979860
polymorphism demonstrated that T- allele carrier was higher among nonresponders
(87.5) in comparison to SVR and control group (42.5 and 65.0
respectively).
VDR (Fok1) rs2228570T polymorphism demonstrated that there was
significant difference regarding C- allele carrier (mutant type) with higher
frequency of C- allele carrier among non-responders (92.5) in comparison
to SVR and control group (42.5 and 65.0 respectively).
VDR Apa1 rs7975232C polymorphism demonstrated that there was
significant difference regarding C- allele carrier with higher frequency of
C- allele carrier among non-responders (92.5) in comparison to SVR and
control group (65.0 and 85.0 respectively).
In Conclusion: Pretreatment vitamin D level is significantly higher in
responder’s patients and can be used as a predictor of response to
combination therapy of HCV. Furthermore, VDR gene polymorphisms
(Fok1 and Apa1)T allele carrier, IL28B polymorphism, pretreatment lower
viral load and lower AFP are independently related to response to
(pegylated) interferon and oral ribavirin therapy in chronic hepatitis C.