In Egypt,Sofosbuvir(SOF)in combination with Dataclasvir(DCV)is the broadly used DAAs with excellent therapeutic profile.This study is designed to explore the relation between IL28B/TLR4 genetic variants and each of th...In Egypt,Sofosbuvir(SOF)in combination with Dataclasvir(DCV)is the broadly used DAAs with excellent therapeutic profile.This study is designed to explore the relation between IL28B/TLR4 genetic variants and each of the followings;HCC development post SOF/DCV treatment,progression to HCC in naı¨ve patients and SOF/DCV therapy outcome.A total of 493 blood samples were collected(controls(n = 70);HCV patients treated with SOF/DCV(n = 252)of whom 65 patients developed HCC,187 patients didn’t develop HCC(125 responders,62 relapsers);naı¨ve HCV patients(n = 171)had early(n = 48),late liver fibrosis(n = 21)and HCC(n = 102)).Both SNPs were genotyped using a TaqMan 50 allelic discrimination assay.At IL28B rs12979860 SNP,the C allele was significantly correlating with the response rate more than T allele(OR 1.9,95%CI 1.29e2.9,p=0.004),while at TLR4 rs4986791 SNP,no association was found(OR 6.5,95%0.57e75.28,p = 0.09).Both SNPs couldn’t detect the probability for HCC emergence after treatment.In naı¨ve patients,the protective alleles were detected in their lowest frequency in HCC patients(p = 0.1,for rs12979860 and,p = 0.001 for rs4986791).SOF/DCV combination improved SVR rates in HCV genotype 4a infected patients regardless of IL28B genotype,with the best rates in those lacking the T allele.展开更多
基金We would like to acknowledge the Science and Technology Development Fund in Egypt(STDF)(Grant No.15002)to Reham DAWOOD for financially supporting the current research.
文摘In Egypt,Sofosbuvir(SOF)in combination with Dataclasvir(DCV)is the broadly used DAAs with excellent therapeutic profile.This study is designed to explore the relation between IL28B/TLR4 genetic variants and each of the followings;HCC development post SOF/DCV treatment,progression to HCC in naı¨ve patients and SOF/DCV therapy outcome.A total of 493 blood samples were collected(controls(n = 70);HCV patients treated with SOF/DCV(n = 252)of whom 65 patients developed HCC,187 patients didn’t develop HCC(125 responders,62 relapsers);naı¨ve HCV patients(n = 171)had early(n = 48),late liver fibrosis(n = 21)and HCC(n = 102)).Both SNPs were genotyped using a TaqMan 50 allelic discrimination assay.At IL28B rs12979860 SNP,the C allele was significantly correlating with the response rate more than T allele(OR 1.9,95%CI 1.29e2.9,p=0.004),while at TLR4 rs4986791 SNP,no association was found(OR 6.5,95%0.57e75.28,p = 0.09).Both SNPs couldn’t detect the probability for HCC emergence after treatment.In naı¨ve patients,the protective alleles were detected in their lowest frequency in HCC patients(p = 0.1,for rs12979860 and,p = 0.001 for rs4986791).SOF/DCV combination improved SVR rates in HCV genotype 4a infected patients regardless of IL28B genotype,with the best rates in those lacking the T allele.
