الفهرس | Only 14 pages are availabe for public view |
Abstract Hepatitis C virus (HCV) infection is a global health problem. It is the leading cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC). The global distribution of HCV genotypes follows a characteristic geographic pattern. The interaction between the virus and the host immune system is important in determining the course of infection and the response to therapy. Polymorphisms at the interleukin 28B (IL-28B) gene largely influence treatment responses to direct acting antiviral drugs (DAA) including Sofosbuvir, Daclatasvir with or without Ribavirin. Single nucleotide polymorphisms (SNPs) in IL-28B gene has been identified to be associated with HCV treatment response in a genome-wide association study (GWAS) found that SNP at IL-28B (rs12979860) gene is the strongest host genetic predictor of sustained virological response (SVR) in hepatitis C genotype1. Among the three genotypes of IL-28B, CC genotype is associated with 2 to 3 fold increase in SVR as compared with either CT or TT genotypes. Objectives: This study aimed to assess if there is a relationship between the functional SNP of IL-28B (rs12979860) gene and HCV treatment response to DAA in an Egyptian population. Methods: This case-control descriptive analytical study included 200 subjects, 100 HCV patients who received Sofosbtuvir, Dacatasvir ± Ribavirin (50responders&50 non-responders) compared to 100 age and sex matched healthy control subjects. 7 The patients were recruited from Tropical clinic in Fayoum University Teaching Hospital during a period extending from May, 2019 till February, 2020. All samples were subjected to genomic DNA analysis of SNP of IL-28B gene (rs12979860) using Real Time PCR. Results: The SNP IL-28B gene (rs12979860) was not statistically significantly different between HCV patients compared to controls (p > 0.05). Moreover, there was a statistically significant difference (p value<0.05) between the drug resistant HCV patients and the drug responsive cases as regards CT genotypes.Additionally, there was a high statistically significant difference in TT genotype (p-value<0.01). CC represents our reference genotype. The C allele was also higher among drug responsive patients while the T allele was higher among drug resistant patients with a high statistically significant difference of p-value <0.01. Conclusion: Our study revealed that there is a significant link between IL-28Bgene (rs12979860) polymorphism and HCV treatment response to DAA. CC genotype is a good predictor of SVR in chronic hepatitis C genotype 4 Egyptian patients and this genotype may influence the effect of treatment Key words: IL-28Bgene (rs12979860), single nucleotide polymorphisms, sustained virological response. |