Introduction Standard therapy for chronic hepatitis C virus (HCV) infection consists of pegylated interferon-? and ribavirin. This treatment is only effective in 40-50% of patients with HCV genotype 1 (G1) infections. The IL28B single nucleotide polymorphism (SNP) is well described but other host genetic factors may influence treatment response.

Aims/Background This study investigated associations between host genetic variation and treatment response to standard therapy in HCV genotype 1 and 3 (G3) infected patients. The genetic markers investigated comprised four IL28B SNPs (G1 n=89; G3 n=82): rs12979860, rs8099917, rs4803221, rs7248668; and HLA-C alleles (G1 n=71; G3 n=67): C1/C1, C1/C2 or C2/C2.

Method Nucleic acids were extracted from serum and plasma and SNP typing was performed by allelic discrimination real-time PCR, PCR-SSP and sequencing approaches.

Results For HCV genotype 1 infections, the IL28B SNP rs12979860 was the most significant genetic marker for predicting non-response to treatment, with a positive predictive value of 81.3% in patients homozygous for the T allele. HLA-C2 homozygosity was found to be significantly associated with non-response in genotype 1 infections (p=0.023). 19% (7/37) of non-responders were HLA-C2/C2 homozygoytes compared to no patients (0/34) with this genotype who achieved SVR. All HCV genotype 1 patients homozygous for HLA-C2, who did not achieve SVR, were rs12979860 heterozygotes (C/T). For HCV genotype 3 patients, no significant association was observed between HLA-C and non-response to treatment (p=0.09).⇓ ⇓

Prediction measures were calculated using non-response as the outcome of interest, and each genetic variant as the “test” for non-response. The * notation refers to all genotypes containing that allele.⇓

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Figure 1

Frequency of HLA-C1/C2 in HCV genotype 1 and 3 responders versus non-responders.

Conclusion A combination of IL28B rs12979860 and HLA-C host genotype may better predict treatment outcomes to standard therapy for HCV genotype 1 infections.