الفهرس 
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Abstract
HBV infection is an inflammatory illness of the liver. It is a serious threat to human health as there are about two billion people in¬fected with HBV all-over the world, 360 million have chronic infection, and nearly 1.2 million die annually from HBV-related liver disease. In Egypt is considered among area of intermediate endemicity (2-8%) of HVB.
HLA is an inherent system of allo-antigens, which are the products of genes of MHC. They encode peptides involved in host immune response, also they are important in tissue transplantation and are associated with a variety of infectious, autoimmune, and inflammatory diseases. Moreover, HLA loci display an unprecedented degree of diversity and the distribution of HLA alleles and haplotypes among different populations is considerably variable.
In vitro studies show that HBs-Ag and HBc-Ag expressing cells serve as targets for MHC class I-restricted CTLs that are generated from both acute and chronic hepatitis B patients. Recent genome-wide association studies have revealed some polymorphisms in the HLA region to be associated with liver diseases, susceptibility for HBV infection, chronic HBV infection or even spontaneous HBV clearance.
IP-10 is produced during periods of infection and inflammation in response to type I and type II interferon such as IFN-α/β and IFN-γ, respectively. This chemokine plays important roles in appropriate immune response and is one of the main chemokines in the recruitment of immune cells to the liver and induction of cellular immunity against viral infections, especially HBV.
Therefore, this study aimed to investigate HLA-DQ-rs3920, HLA-DP-rs3077 SNP and IP-10 serum levels relations to nucleoside/ nucleotide analogues (NAs) treatment among CHB infected Egyptian patients. The current study was conducted on 30 HBV infected patients who were divided into 3 groups; naïve, responder and non-responder HBV patients. Ten healthy volunteers, matched in age and sex, were included in the study as control groups.
The mean age of naïve, responder, non- responder HBV patients and healthy control was 29.8 ± 3.8, 36.1± 9.9, 37.9 ± 9.5 and 32.1 ± 5.8 years, respectively. The male to female ratio among all the 40 subjects included in our study was around 11:9. There was no statistical significant differences between the studied groups regarding age and sex; where P= 0.064 and 0.063, respectively.
For all subjects under the study, the following tests were performed; assessment of liver functions’ tests, measuring HBV DNA levels using real time PCR, measurement of IP-10 levels using ELISA and genotyping of HLA-DP-rs3077 and -DQ rs3920 SNP using 5’ nuclease assay in an StepOne™ Real-Time PCR System.
According to the present laboratory investigations, liver functions were markedly deteriorated in HBV patients compared to control group. Viral markers showed statistical significant differences between HBV responder patients and other groups; where all of them were HBe-Ag negative, most of them were HBe-Ab positive and nearly all were HBc-Ab positive. HBV-DNA levels were significantly increased among naïve HBV patients compared to responder and non-responder groups (P =0.001).
Concerning HLA-DP-rs3077 the AA genotype was highly expressed among naïve HBV patients; where all of them carry this allele. This may indicate that carrying of HLA-DP-rs3077 AA allele was significantly associated with HBV susceptibility (P=0.018). The expression of rs3077 allele A was higher among naïve and non-responder HBV patients while expression of rs3077 allele G was higher among responder HBV patients and healthy controls, but no statistically significant. This may be due to the small sample size included in this study. So allele A of HLA-DP-rs3077 could be identified as HBV risk allele and may have a role in resistance to treatment.
Correlation analysis showed statistically significance association between HLA-DP-rs3077 and both ALT level in responder HBV group (P= 0.022) and Albumin level in non-responder HBV group (P = 0.036).
While for HLA-DQ-rs3920 the GG genotype was highly expressed in the different groups of HBV patients (80%, 70% and 80% of naïve, responder, non- responder HBV infected patient groups). But, there were no statistical significant differences between the studied groups. Correlation analysis revealed association between HLA-DQ-rs3920 AA genotype and HBV-DNA in non-responder. So the current study could identify allele G of rs3920 as HBV risk allele as it was strongly associated with HBV infection while allele A of rs3920 was strongly associated with resistance to treatment when compared to GG or GA genotypes.
In addition, the present data demonstrates that IP-10 level was significantly increased among non-responder group compared with naïve, responder and control groups
(P = 0.011). Also there was significance increase of IP-10 level in non-responder group of HLA-DP-rs3077 AG allele (P= 0.047) and of HLA-DQ-rs3920 GG allele
(P = 0.001). These data demonstrate that IP-10 considered as an intermediate indicator
(r = 0.54). All these results provide evidences on role of IP-10 as promising predictor of response to treatment among HBV infected patients