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 naïve 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); naïve HCV patients (n = 171) had early (n = 48), late liver fibrosis (n = 21) and HCC (n = 102)). Both SNPs were genotyped using a TaqMan 5' 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 1.29-2.9, p = 0.004), while at TLR4 rs4986791 SNP, no association was found (OR 6.5, 95% 0.57-75.28, p = 0.09). Both SNPs couldn't detect the probability for HCC emergence after treatment. In naïve 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.
Keywords: DAAs; DAAs, Direct acting antiviral agents; DCV; DCV, Dataclasvir; HCC; HCC, Hepatocellular carcinoma; HCV; HCV, hepatitis C virus; IFNλ, Type III IFNs; IL28B; ISGs, interferon-stimulated genes; JAK/STAT, Janus kinase/signal transducers and activators of transcription; PAMPs/DAMPs, pathogen/damage associated molecular patterns; SNP, single nucleotide polymorphism; SOF; SOF, Sofosbuvir; SVR, sustained virological response; TLR4; TLRs, toll like receptors.
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