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Amino Acid Substitution in HCV Core Region and Genetic Variation near the IL28B Gene Affect Viral Dynamics during Telaprevir, Peginterferon and Ribavirin TreatmentAkuta N.a · Suzuki F.a · Hirakawa M.a · Kawamura Y.a · Yatsuji H.a · Sezaki H.a · Suzuki Y.a · Hosaka T.a · Kobayashi M.a · Kobayashi M.b · Saitoh S.a · Arase Y.a · Ikeda K.a · Chayama K.d · Nakamura Y.c · Kumada H.a
aDepartment of Hepatology, and bLiver Research Laboratory, Toranomon Hospital, cLaboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, and dDepartment of Medical and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan
Objectives: Genetic variation near the IL28B gene and substitution of aa 70 and 91 in the core region of HCV-1b are useful as predictors of treatment efficacy to telaprevir/pegylated interferon (PEG-IFN)/ribavirin, but its impact on viral dynamics is not clear. Methods: This study investigated predictive factors of viral dynamics during 12- or 24-week regimen of triple therapy in 80 Japanese adults infected with HCV-1b. Results: After 24 h of commencement of treatment, the proportion of patients with Arg70 and Leu91 substitutions in the core region who showed ≥3.0 log drop in HCV RNA level was significantly higher than that of patients with Gln70 (His70) and/or Met91. At 8 and 12 weeks, HCV RNA loss rate of patients with rs8099917 genotype TT near IL28B gene was significantly higher than that of patients with non-TT. Multivariate analysis identified substitution of aa 70 and 91 as a predictor of ≥3.0 log fall in HCV RNA level at 24 h (Arg70 and Leu91) and SVR (Arg70), and rs8099917 (TT) as a predictor of HCV RNA loss at 12 weeks and SVR. Conclusions: This study identified genetic variation near IL28B gene and aa substitution of the core region as predictors of viral dynamics during triple therapy.
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