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Authors

  • Marco Antonio Montes-Cano M.D.,

    1. Servicio de Inmunología, Hospital Universitario Virgen del Rocío/Instituto de Biomedicina de Sevilla, Seville, Spain
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  • José Raúl García-Lozano M.D.,

    1. Servicio de Inmunología, Hospital Universitario Virgen del Rocío/Instituto de Biomedicina de Sevilla, Seville, Spain
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  • Cristina Abad-Molina M.D.,

    1. Servicio de Inmunología, Hospital Universitario Virgen del Rocío/Instituto de Biomedicina de Sevilla, Seville, Spain
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  • Fuensanta Torrecillas M.D.,

    1. Servicio de Inmunología, Hospital Universitario Virgen del Rocío/Instituto de Biomedicina de Sevilla, Seville, Spain
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  • Almudena Torres M.D.,

    1. Servicio de Enfermedades Infecciosas, Hospital Universitario Virgen del Rocío/Instituto de Biomedicina de Sevilla, Seville, Spain
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  • Luis Felipe Lopez-Cortes M.D., Ph.D.,

    1. Servicio de Enfermedades Infecciosas, Hospital Universitario Virgen del Rocío/Instituto de Biomedicina de Sevilla, Seville, Spain
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  • Antonio Núñez-Roldán M.D., Ph.D.,

    1. Servicio de Inmunología, Hospital Universitario Virgen del Rocío/Instituto de Biomedicina de Sevilla, Seville, Spain
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  • María Francisca González-Escribano Ph.D.

    1. Servicio de Inmunología, Hospital Universitario Virgen del Rocío/Instituto de Biomedicina de Sevilla, Seville, Spain
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  • This work was supported by Fondo de Investigaciones Sanitarias (07/0061) and Plan Andaluz de Investigación (CTS-0197).

  • Potential conflict of interest: Nothing to report.

Reply:

We thank Huang and colleagues for their comments on our article recently published in HEPATOLOGY.1 In this study, we found an overrepresentation of individuals with the interleukin-28B (IL-28B) genotype predictor of sustained virological response (rs12979860CC) among patients infected by non–genotype 1 (non-G1) hepatitis C virus (HCV). In their study, Huang et al. confirmed our results by genotyping another IL-28B single-nucleotide polymorphism, rs8099917 (which is also associated with the response to treatment), in a large Asian HCV cohort that included G2-infected patients at a high rate. We also confirmed our previous results in a new cohort consisting of 182 patients coinfected with human immunodeficiency virus and HCV who had a higher rate of non-G1 infection (48% with G1, 1% with G2, 36% with G3, and 15% with G4). The distribution of IL-28B genotypes among individuals stratified by their viral genotypes was similar to the distribution in the cohort previously reported. Figure 1 displays the results from the mixing of both cohorts; the CC genotype was underrepresented in patients infected by G1 (36%) or G4 (33%) and was overrepresented in patients infected with G2 (85%) or G3 (64%) in comparison with our uninfected population (45%). Thus, both the IL-28B variants and viral genotypes predicting a sustained virological response and the factors predicting an unsustained virological response were found together more often than expected. In conclusion, our results, together with those reported by Huang et al. in their letter and by others,2, 3 draw a scenario in which genetic factors from the host and virus are found to be unexpectedly associated. Although these results are difficult to explain with our current knowledge, it is necessary to take these findings into account because the relationship between the virus and the host genetic background can act as a confounding factor introducing study bias.

Figure 1.

Rates of the IL-28B rs12979860CC genotype among patients infected with various HCV genotypes (G1-G4). The rates of patients infected with G1 and G4 or G2 and G3 are displayed. A comparison of the G1+G4 group and the G2+G3 group was statistically significant (P = 7.13 × 10−9).

Marco Antonio Montes-Cano M.D.*, José Raúl García-Lozano M.D.*, Cristina Abad-Molina M.D.*, Fuensanta Torrecillas M.D.*, Almudena Torres M.D.†, Luis Felipe Lopez-Cortes M.D., Ph.D.†, Antonio Núñez-Roldán M.D., Ph.D.*, María Francisca González-Escribano Ph.D.*, * Servicio de Inmunología, Hospital Universitario Virgen del Rocío/Instituto de Biomedicina de Sevilla, Seville, Spain, † Servicio de Enfermedades Infecciosas, Hospital Universitario Virgen del Rocío/Instituto de Biomedicina de Sevilla, Seville, Spain.

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