Abstract

Egypt has one of the highest prevalences of hepatitis C virus (HCV) infection worldwide. Although the IL28B gene polymorphism has been shown to modify the course of chronic HCV infection, this has not been properly assessed in the Egyptian population. The IL28B rs12979860 single nucleotide polymorphism (SNP) was therefore examined in 256 HCV-infected Egyptian patients (group II) at different stages of disease progression and in 48 healthy volunteers (group I). Group II was subdivided into GII-A (chronic hepatitis patients, n=119), GII-B (post hepatitis cirrhosis, n=66) and GII-C (HCC on top of cirrhosis, n=71). The C/T genotype was the commonest in all groups. It was more frequent in GI (52%) than in GII (48%). There was no significant difference in the frequency of C/T and C/C or T/T genotypes between groups and subgroups (p=0.82). Within the subgroups; the C/C genotype was more common in GII-B while C/T and T/T genotypes were more common in GII-C, though with no significant difference (p=0.59 and p=0.80). There was no significant association between IL28B rs12979860 SNP and viral load, ALT, AFP level, METAVIR scores for necro-inflammation and fibrosis, and Child-Pugh classification. 1) IL28Brs12979860 C/T genotype is the commonest genotype in HCV-associated CH and HCC in Egypt. 2) IL28Brs12979860 polymorphisms are not associated with disease progression or aggression (histological staging, severity of fibrosis in CH or the incidence of post-HCV HCC). 3) Differences in IL28Brs12979860 genotypes could be a consequence of environmental or ethnic variation.

Highlights

  • The prevalence of hepatitis C virus (HCV) in Egypt exceeds 18% of the general population

  • Studied patients were further categorized into subgroups according to the stage of the disease progression as follows: group IIA: n=119 representing chronic hepatitis C virus infected patients with no liver cirrhosis, group IIB: n=66 patients with post-hepatitis C virus liver cirrhosis, group IIC: n=71 patients with hepatocellular carcinoma (HCC) post hepatitis C virus cirrhotic liver

  • The IL-28 rs12979860 C/T polymorphism were studied in these groups as well as in the control group and it was reported that in control subjects, the genotype frequencies did not depart from those expected on the basis of Hardy-Weinberg equilibrium (p-value=0.71), the same issue was observed in the other studied groups with p-values=0.87, 0.94 and 0.59 for CH “Group II A”, cirrhotic and HCC groups respectively

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Summary

Introduction

The prevalence of hepatitis C virus (HCV) in Egypt exceeds 18% of the general population. The contribution of the innate immune system to disease outcome in HCV infected patients was further supported by a series of studies on single nucleotide polymorphisms (SNPs) in the IL28B gene region, which predicts spontaneous and type 1 IFN induced clearance of HCV infections (Rauch et al, 2010). Multiple genome-wide association studies (GWAS) have recently identified SNPs near the IL28B gene (encoding IFN-λ3), which are strongly associated with spontaneous and treatment-induced clearance of HCV infections (Rauch et al, 2010) One of these SNPs is rs12979860 C/T, it is pivotal in predicting the outcome of HCV infections (Thomas et al, 2009). Conclusions: 1) IL28Brs12979860 C/T genotype is the commonest genotype in HCV-associated CH and HCC in Egypt. 2) IL28Brs12979860 polymorphisms are not associated with disease progression or aggression (histological staging, severity of fibrosis in CH or the incidence of post-HCV HCC). 3) Differences in IL28Brs12979860 genotypes could be a consequence of environmental or ethnic variation

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