الفهرس 
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Abstract
More than 95% of adult infected with HBV show acute self-limited infection and eventually eliminate the virus. In contrast, about 90% of people exposed to HBV in early childhood develop chronic infection. The specificity of the virus and the host’s antiviral immune responses together determine the outcome of HBV infection.
It is generally believed that viral genome variation, viral titers and inhibition of viral components against the host immune system are associated with persistent infection and liver damage. The dysfunction of innate immune cells (NK cells, monocyte/macrophages, NKT cells, etc.) and adaptive immune cells (antigen-presenting cells, T cells, B cells) is a key factor leading to virus clearance failure and liver inflammation.
Additionally, human genes polymorphisms have been reported worldwide to contribute to host susceptibility to chronic HBV and HBV-clearance, of which, IL-4, CTLA4, TLR, TNF, HLA genes, etc.
Research is underway to examine changes of immune systems and the association between genetic polymorphisms and viral susceptibility in order to discover CHB therapy and prognosis related immune molecule and genes.
The cytotoxic T-lymphocyte–associated antigen 4 (CTLA- 4) and programmed death 1 (PD-1) immune checkpoints are negative regulators of T-cell immune function. The over expressions of PD-1 and CTLA-4 in patients with chronic HBV infection have been shown to associate with functional impairment of virus-specific T cells.
The aim of this study was to analyze correlation between PD1 (+8669 G/A) and CTLA-4 (+49 A/G) polymorphism and susceptibility of HBV infection and disease progression in Egyptian population.
The present study was conducted during the period from November 2017 to September 2020 in the National Liver Institute, Menoufia University. The study included 70 chronic HBV patients from inpatient and outpatient clinics and 25 healthy volunteers as a control group.
According to their clinical diagnosis the patients were divided into three groups. First group included patients with chronic hepatitis B (CHB), second group included HBV-related liver cirrhosis group (LC) and third group included HBV-related hepatocellular carcinoma group (HCC). While the fourth group included 25 healthy volunteers as a control group.
All patients and controls were subjected to the following laboratory investigations: Liver function tests, Complete blood count, Hepatitis B markers, Molecular detection of PD1 (+8669 G/A) genotypes by bidirectional PCR amplification of specific alleles (Bi-PASA) and genotyping of CTLA-4 (+49 A/G) polymorphism using the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP).
The current study showed that:
PD1 (+8669) polymorphism may play a role in chronic HBV infection in the Egyptian population.
Genotype GG at PD1 (+8669) gene was protective against HBV infection, while AA and GA genotypes increase the risk to develop a chronic infection among Egyptian patients.
PD1 (+8669) polymorphism may be implicated in the susceptibility to chronic HBV infection with AA genotype and A allele as a predisposing and the GG genotype and G allele might be preventive factors for chronic HBV infection.
PD-1 (+8669) alleles had no significant association with risk of progression of CHB into LC.
While, PD1 (+8669) polymorphism appears to be primarily associated with the development of HCC in chronic HBV patients.
There was no significant differences in CTLA-4 (+49 A/G) genotypes and alleles among chronic HBV patients.
There was no association of CTLA-4 (+49 A/G) polymorphism and risk of progression of CHB to LC.
CTLA-4 (+49 A/G) polymorphism seems to be associated with the development of HCC in chronic HBV infection as the GA genotype was predominant in HCC patients (60%) compared to non HCC patients (26.2%).