title: Determinants of response to triple therapy of telaprevir, peginterferon, and ribavirin in previous non-responders infected with HCV genotype 1.
abstract: Patients who do not achieve sustained virological response to telaprevir/peginterferon (PEG-IFN)/ribavirin need to be identified. Predictive factors of virological response to the triple therapy in non-responders to previous PEG-IFN/ribavirin therapy are not clear. The aims of this study were to determine the predictive factors of virological response to a 24-week regimen of triple therapy in 15 non-responders to previous PEG-IFN/ribavirin therapy among 61 Japanese adults infected with HCV genotype 1. Overall, sustained virological response and end-of-treatment response were achieved by 27% and 60%, respectively. Telaprevir-resistant variants (by direct sequencing) appeared during or after treatment in 82% of patients who did not show sustained virological response, but disappeared at the end of study, except for one patient with resistant variant at baseline. Substitution at aa 70 (Arg70) and type of previous response to PEG-IFN/ribavirin (partial response) were identified as significant determinants of sustained virological response. In addition, alpha-fetoprotein level (<10 µg/L) and type of previous response (partial response) were identified as significant determinants of end-of-treatment response. Prediction of response to therapy based on the combination of these factors had high sensitivity, specificity, positive, and negative predictive values. In conclusion, this study identified amino acid substitution of the core region, alpha-fetoprotein level, and type of previous response as predictors of virological response to telaprevir/PEG-IFN/ribavirin in patients infected with HCV genotype 1b who had not responded to previous PEG-IFN/ribavirin therapy.
authors.affiliation: Department of Hepatology, Toranomon Hospital, and Okinaka Memorial Institute for Medical Research, Tokyo, Japan. akuta-gi@umin.ac.jp
authors.forename: Norio
authors.initials: N
authors.lastname: Akuta
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Suzuki
authors.forename: Yuya
authors.initials: Y
authors.lastname: Seko
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kawamura
authors.forename: Hitomi
authors.initials: H
authors.lastname: Sezaki
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hosaka
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Mariko
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Saitoh
authors.forename: Yasuji
authors.initials: Y
authors.lastname: Arase
authors.forename: Kenji
authors.initials: K
authors.lastname: Ikeda
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Kumada
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage*; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000235:genetics / Q000302:isolation & purification*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007372:Interferons / Q000008:administration & dosage*; D007564:Japan; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage*; D011237:Predictive Value of Tests; D012254:Ribavirin / Q000008:administration & dosage*; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D014773:Virology / Q000379:methods*
chemical_list: D000998:Antiviral Agents; D009842:Oligopeptides; D012254:Ribavirin; C486464:telaprevir; D007372:Interferons