Strong prediction of virological response to combination therapy by IL28B gene variants rs12979860 and rs8099917 in chronic hepatitis C genotype 4

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Abstract

BACKGROUND: A strong association between single nucleotide polymorphisms (SNPs) of IL28B and treatment outcomes of pegylated interferon-α (PEG IFNα) and ribavirin (RBV) has been shown in chronic hepatitis C (CHC) patients with genotype 1.<br /><br />AIM: This study aimed to assess two SNPs of IL28B, rs12979860 and rs8099917, in predicting sustained virological responses (SVR) to treatment of CHC patients with genotype 4 (HCV-4). The value of rs8099917 was investigated in carriers of unfavourable genotypes of rs12979860.<br /><br />METHODS: This study included 119 CHC patients with HCV-4 receiving combination therapy. Both SNPs of IL28B were determined by real-time detection polymerase chain reaction.<br /><br />RESULTS: Genotypes CC/CT/TT of rs12979860 were found in 42 (35.3%), 56 (47.1%) and 21 (17.6%) and rs8099917 TT/TG/GG were found in 74 (62.2%), 40 (33.6%) and 5 (4.2%). In carriers of rs12979860 CC and rs8099917 TT, the rate of SVR was 87.5 and 65.7% respectively. In 54 patients heterozygous for the C allele of rs12979860, testing of rs8099917 revealed SVR in 42.3% of carriers of the TT genotype but no such responses in carriers of TG or GG (P < 0.0001, OR = 47.3, 95% CI: 2.33-767.2). By multivariate analysis, predictors of SVR were baseline ALT (P = 0.014, OR = 6.3, 95% CI: 1.45-27.33), rs12979860 CC (P = 0.001, OR = 13.48, 95% CI: 2.95-61.69) and rs8099917 TT (P = 0.027, OR = 7.5, 95% CI: 1.25-44.88).<br /><br />CONCLUSION: In CHC genotype 4 patients, favourable genotypes of both SNPs of IL28B are valuable for predicting SVR. Additional genotyping of rs8099917 in carriers of the heterozygous C allele of rs12979860 can improve the prediction of SVR.

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Ragheb, M. M., Nemr, N. A., Kishk, R. M., Mandour, M. F., Abdou, M. M., Matsuura, K., … Tanaka, Y. (2014). Strong prediction of virological response to combination therapy by IL28B gene variants rs12979860 and rs8099917 in chronic hepatitis C genotype 4. Liver International, 34(6), 890–895. https://doi.org/10.1111/liv.12321

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