IL28B But Not ITPA Polymorphism Is Predictive of Response to Pegylated Interferon, Ribavirin, and Telaprevir Triple Therapy in Patients With Genotype 1 Hepatitis C

被引:104
作者
Chayama, Kazuaki [1 ,2 ,3 ]
Hayes, C. Nelson [2 ,3 ]
Abe, Hiromi [2 ,3 ]
Miki, Daiki [2 ,3 ]
Ochi, Hidenori [2 ,3 ]
Karino, Yoshiyasu [4 ]
Toyota, Joji [4 ]
Nakamura, Yusuke [5 ]
Kamatani, Naoyuki [7 ]
Sezaki, Hitomi [6 ]
Kobayashi, Mariko [6 ]
Akuta, Norio [6 ]
Suzuki, Fumitaka [6 ]
Kumada, Hiromitsu [6 ]
机构
[1] Hiroshima Univ, Grad Sch Biomed Sci, Dept Med & Mol Sci,Div Frontier Med Sci, Programs Biomed Res,Minami Ku, Hiroshima 7348551, Japan
[2] RIKEN, Ctr Genom Med, Lab Digest Dis, Yokohama, Kanagawa, Japan
[3] Hiroshima Univ, Liver Res Project Ctr, Hiroshima 7348551, Japan
[4] Sapporo Kosei Gen Hosp, Dept Gastroenterol, Sapporo, Hokkaido, Japan
[5] Univ Tokyo, Inst Med Sci, Ctr Human Genome, Mol Med Lab, Tokyo 1138654, Japan
[6] Toranomon Gen Hosp, Dept Hepatol, Tokyo, Japan
[7] RIKEN, Ctr Genom Med, Stat Lab, Yokohama, Kanagawa, Japan
关键词
AMINO-ACID SUBSTITUTIONS; SUSTAINED VIROLOGICAL RESPONSE; PEGINTERFERON PLUS RIBAVIRIN; VIRUS CORE REGION; GENETIC-VARIATION; COMBINATION THERAPY; GENOME-WIDE; INTERLEUKIN; 28B; ASSOCIATION; MANAGEMENT;
D O I
10.1093/infdis/jir210
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background. Pegylated interferon, ribavirin, and telaprevir triple therapy is a new strategy expected to eradicate the hepatitis C virus (HCV) even in patients infected with difficult-to-treat genotype 1 strains, although adverse effects, such as anemia and rash, are frequent. Methods. We assessed efficacy and predictive factors for sustained virological response (SVR) for triple therapy in 94 Japanese patients with HCV genotype 1. We included recently identified predictive factors, such as IL28B and ITPA polymorphism, and substitutions in the HCV core and NS5A proteins. Results. Patients treated with triple therapy achieved comparatively high SVR rates (73%), especially among treatment-naive patients (80%). Of note, however, patients who experienced relapse during prior pegylated interferon plus ribavirin combination therapy were highly likely to achieve SVR while receiving triple therapy (93%); conversely, prior nonresponders were much less likely to respond to triple therapy (32%). In addition to prior treatment response, IL28B SNP genotype and rapid viral response were significant independent predictors for SVR. Patients with the anemia-susceptible ITPA SNP rs1127354 genotype typically required ribavirin dose reduction earlier than did patients with other genotypes. Conclusions. Analysis of predictive factors identified IL28B SNP, rapid viral response, and transient response to previous therapy as significant independent predictors of SVR after triple therapy.
引用
收藏
页码:84 / 93
页数:10
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