title: A matched case-controlled study of 48 and 72 weeks of peginterferon plus ribavirin combination therapy in patients infected with HCV genotype 1b in Japan: amino acid substitutions in HCV core region as predictor of sustained virological response.
abstract: Substitution of amino acid (aa) 70 and 91 in the core region of HCV genotype 1b is a useful pretreatment predictor of efficacy of 48-week peginterferon (PEG-IFN) plus ribavirin (RBV) therapy. Here, we determined the efficacy of 72-week PEG-IFN/RBV and the predictive factors to such therapy in a case-control study matched for sex, age, and periods from the start of treatment to initial point of HCV RNA-negative. We compared the treatment efficacy of 72-week regimen in 65 patients with that of 48-week in 130 patients, who were infected with HCV genotype 1b and treated with PEG-IFN/RBV. They consisted mainly of late virological responders (LVR) (HCV RNA-positive at 12 weeks and negative at 24 weeks after start of treatment). Sustained virological response (SVR) was achieved by 61.5% and 32.3% of patients of the 72- and 48-week groups, respectively, while non-virological response was noted in 9.2% and 29.2% of the respective groups. Multivariate analysis identified substitution of aa 70 and 91 (Arg70 and/or Leu91) and duration of treatment (72-week) as independent parameters that significantly influenced SVR. For Arg70 and/or Leu91 of core region, SVR rate was significantly higher in 72- (68.0%) than 48-week group (37.8%). For wild-type of ISDR, SVR rate was significantly higher in 72- (61.2%) than in 48-week group (29.3%). We conclude that 72-week PEG-IFN/RBV improves SVR rate for LVR, especially those with Arg70 and/or Leu91 of core region or wild-type of ISDR. Substitution of aa 70 and 91 is also a useful pretreatment predictor of response to 72-week PEG-IFN/RBV.
authors.affiliation: Department of Hepatology, Toranomon Hospital, 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: Miharu
authors.initials: M
authors.lastname: Hirakawa
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kawamura
authors.forename: Hiromi
authors.initials: H
authors.lastname: Yatsuji
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; D019943:Amino Acid Substitution / Q000235:genetics*; D000998:Antiviral Agents / Q000627:therapeutic use*; D016022:Case-Control Studies; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000235:genetics* / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D007564:Japan; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D011092:Polyethylene Glycols; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use*; D017422:Sequence Analysis, DNA; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b