[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to assess the impact of genetic variants of oligoadenylate synthetase 1 (OAS1) single-nucleotide polymorphism (SNP) rs10774671 at the exon 7 splice acceptor site on liver fibrosis progression and hepatitis C virus (HCV) outcome in Egyptian HCV genotype 4 patients. In this study, 195 subjects were enrolled; 60 controls and 135 chronic HCV genotype 4 patients with different fibrosis grades. All subjects were genotyped for OAS1 SNP rs10774671 polymorphism by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. There was an increasing trend of liver fibrosis progression as 52.9% GG, 73.6% GA, and 83.3% AA genotypes were detected in late fibrosis patients (p = 0.025). The AA genotype was higher in the late fibrosis group than in the early fibrosis group (83.3% vs. 16.7%) (p = 0.001). The A allele was significantly affecting the liver fibrosis progression rate, more than the G allele (p = 0.001). The multivariate analysis showed that the OAS1 GA and AA genotypes were independent factors associated with liver progression (p = 0.009, odds ratio [OR] 3.467, 95% confidence interval [CI] 1.273-7.584). In addition, the A allele was associated with liver fibrosis progression (p = 0.014, OR 2.525, 95% CI 1.157-4.545). The polymorphism at OAS1 exon 7 rs3741981 might be a potential genetic marker and can be useful in the assessment of liver fibrosis progression and disease outcome in HCV-infected patients.
[Show abstract][Hide abstract] ABSTRACT: Antibody mediated neutralization and specific cell mediated immunity are necessary to combat HCV infection. Viral load reduction following administration of non adjuvanted envelope peptide vaccine was investigated in chronic HCV-infected patients who did not respond to interferon and ribavirin (IFN+RBV) treatment. The roles of humoral and cellular arms in viral load decline were examined and tolerability was evaluated.
In an open-label study, patients with mild CHC (genotype 4a) were enrolled in 2 groups of 14 patients each; they received subcutaneous injections of Cenv3 at 648μg×3 monthly doses (group I) and 324μg×6 biweekly doses (group II). Vaccine sera were examined for specific antibody titers against vaccine epitopes by ELISA, HCV RNA levels by real-time PCR and specific CD4(+)/CD8(+) T lymphocytes by enzyme-linked immunospot assay (ELIspot). Safety of Cenv3 vaccination was tested on bases of changes in liver functions, kidney function and blood cell counts.
Cenv3 induced significant in antibody mediated viral neutralization and cellular responses with remarkable decline of HCV RNA in about two thirds of patients under study. The product is safe and tolerable with slight improvement in liver functions and platelet counts.
Although, humoral and cellular arms of the immune system are usually impaired in CHC, the selected envelope epitopes were able to induce responses sufficient to reduce significantly viral RNA concentrations in chronic HCV-infected patients shown to be non responders to standard of care treatment. The observed immunogenicity and tolerability of Cenv3 paves the road for further studies toward development of a prophylactic vaccine against HCV. The clinical trial was registered in the ClinicalTrials.gov; under the identifier no.: NCT01718834.
[Show abstract][Hide abstract] ABSTRACT: IL28B single nucleotide polymorphisms (SNPs) play important roles in the management of hepatitis C virus (HCV) infections and are strongly associated with spontaneous and treatment-induced HCV clearance.
In the present study, the association between IL28B variants and the progression of HCV infection in Egyptian patients infected with type 4a virus will be examined.
Frequencies of the protective genotype C/C of SNP, rs12979860 were determined in healthy subjects, spontaneous resolvers, and chronic HCV type 4 patients with low F scores and in patients with end stage liver disease (ESLD). This study included a total of 404 subjects. Patients infected with HCV type 4a (n = 304) were divided into; chronic hepatitis C (CHC) with low F scores (CHC, n = 110), end stage liver disease (n = 110), liver cirrhosis (LC) (n = 35) and hepatocellular carcinoma (HCC) patients (n = 75), spontaneous resolvers of HCV infection (n = 84) were also included. A healthy group representing the Egyptian population (n = 100) was also included in the genotyping of IL28B. The later was typed via a polymerase chain reaction based restriction fragment length polymorphism (PCR-RFLP) assay analysis on purified genomic DNA extracted from all individuals.
A significant increase (P < 0.0005) was observed in frequencies of IL-28B rs12979860 C/C genotypes in the healthy population, than in the CHC, LC and HCC groups (C/C = 48%, 13%, 0%.and 0% respectively). On the other hand the C/C genotype was significantly higher (P < 0.0005) in spontaneous resolvers than in healthy subjects. A comparable significant increase in the frequency of C/T allele accompanied by mild elevation of T/T allele frequency, were detected along the progression towards ESLD.
Genotype C/C is associated with viral clearance during acute infection. The sharp decline in the C/C genotype from healthy to CHC subjects and the total absence of the C/C genotype in ESLD suggests a central role of this genotype against HCV disease progression.