الفهرس 
TitleOnly 14 pages are availabe for public view
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Abstract
Hepatitis C virus (HCV) infection represents the most common blood-borne viral infection for which a vaccine is still lacking, An estimated 3% of the world’s population is infected, representing approximately 200 million individuals. The control of the acute infection depends on both host- and viral-related factors. However, in the majority of acutely HCV infected individuals, these responses are insufficient to clear the virus and most of HCV infections persists, with up to 80% of all cases leading to chronic hepatitis, eventually associated with liver fibrosis, cirrhosis and/or hepatocellular carcinoma.
HCV antiviral drug development has been remarkable. The availability of pangenotypic direct-acting antivirals with excellent efficacy and good tolerability profiles offer a unique opportunity to achieve HCV elimination worldwide. IFN-free DAA combinations can now cure HCV in more than 95% of patients with HCV infection after 8-12 weeks of treatment.
Type III interferons (IFN-III), which include IFNL1, IFNL2, IFNL3, and IFNL4, are antiviral cytokines thought to act primarily at epithelial surfaces. Like type I interferons (IFN-I), IFN-III induce hundreds of interferon-stimulated genes (ISGs). Results from genome-wide association studies (GWAS) identified common inherited genetic markers that were associated with response to hepatitis C virus treatment and spontaneous clearance of the infection. Single nucleotide polymorphisms (SNPs) in the interferon lambda 4 (IFNL4)-gene are predictors for treatment success in patients with hepatitis C virus (HCV) infection.
ERAPs, including ERAP1 and ERAP2, were initially identified as homologues of human placental leucine aminopeptidase or insulin regulated aminopeptidase, and they belong to the oxytocinase subfamily of the M1 zinc metallopeptidases family. They are expressed in various human tissues, such as the heart, placenta, and spleen, and are regulated by interferon-γ (IFN-γ). there are some polymorphisms in natural ERAP gene that might alter ERAP activity by directly affecting catalysis, altering substrate binding, or modulating domain rearrangements; thus, ERAP gene polymorphisms have been associated with autoimmunity and other HLA-associated disease. ERAP1 allotypes modified the repertoire of virus specific CD8+ T cell epitopes in a patient with hepatitis C virus.
The current study aimed to appraise the influence of interferon lambda 4 (IFNλ4 rs73555604) and endoplasmic reticulum aminopeptidases polymorphism (ERAP1 rs26618) on the response to treatment with direct acting anti-viral agents in hepatitis C virus infected patients.
It was conducted on 80 HCV infected patients which divided itno responder and non responder, and 20 healthy volunteers as control group. All patients were treated with sofosbuvir (Sovaldi, 400mg, daily) + daclatsvir (60mg, daily) ± ribavirin for 12 weeks. Healthy volunteers were age and sex matched with the HCV infected patients.
Detection of Interferon lambda 4(IFN-λ-4 rs73555604) and endoplasmic reticulum aminopeptidases (ERAP rs26618) polymorphism was done by DNA extraction technique using (QIAamp DNA Blood Mini Kit).
Summary, C onclusion and Recommendations
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Results revealed that the allelic distribution of IFN-λ-4 rs73555604 in HCV infected patients and control group was significantly different, and the T-allele was associated with decreased treatment response compared with the C-allele (P =.006, OR = 2.581*, 95%CI:1.321- 5.046) and both TC and TT genotypes was significantly different between all participants in comparison to CC genotype.
Also the allelic and genotypic frequencies of, rs26618 in the ERAP1 gene was compared between HCV infected patients (responders and non responders) and control group and found that the T-allele was associated with decreased treatment response compared with the C-allele (P =.001, OR = 3.316*, 95%CI: 1.697-6.479. Also TC genotype was significantly different between responders and non responders in comparison to both CC and TT genotypes.
from all results and studies we can conclude that IFN Interferon lambda 4(IFN-λ-4 rs73555604) and endoplasmic reticulum aminopeptidases (ERAP rs26618) polymorphism have a significant role on the response of DAA in chronic hepatitis C patients.
Recommendations
• To study other polymorphisms of both ERAP and IFN-λ and their effect on treatment response.
• To study the expression profile of other genes which may affect response to treatment.
• To study these genetic polymorphism with different regimens of treatment.