title: Factors of response to pegylated interferon/ribavirin combination therapy and mechanism of viral clearance.
abstract: OBJECTIVE
  This study explores viral factors of the interferon (IFN) and ribavirin (RBV) resistance-determining region (IRRDR), the IFN sensitivity-determining region (ISDR) and the core protein, and host factor interleukin 28B associated with response to pegylated IFN (PEG-IFN) and RBV combination therapy, and the correlation of viral and host factors with IFN-λ1.
  
  
  METHODS
  A total of 58 patients underwent PEG-IFN/RBV combination therapy for 48 weeks. The pretreatment factors associated with rapid virological response (RVR) and sustained virological response (SVR) were analyzed. Pretreatment IFN-λ1 serum levels were compared with the viral and host factors.
  
  
  RESULTS
  Univariate analysis showed that IRRDR ≥6 and ISDR ≥2 were significant pretreatment predictors of RVR, and multivariate analysis identified IRRDR ≥6 and hemoglobin as significant predictors of SVR. Pretreatment IFN-λ1 was significantly higher in the SVR group than in the non-SVR group and also in the IRRDR ≥6 group than in the IRRDR ≤5 group.
  
  
  CONCLUSIONS
  IRRDR ≥6 was the only significant predictor of SVR and was correlated with IFN-λ1. High serum levels of IFN-λ1 may be conducive to effective PEG-IFN/RBV combination therapy because of the immunomodulatory system.
authors.affiliation: Department of Pharmacy, Kobe Asahi Hospital, Kobe, Japan.
authors.forename: Kayo
authors.initials: K
authors.lastname: Sugimoto
authors.forename: Soo Ryang
authors.initials: SR
authors.lastname: Kim
authors.forename: Ahmed
authors.initials: A
authors.lastname: El-Shamy
authors.forename: Susumu
authors.initials: S
authors.lastname: Imoto
authors.forename: Kenji
authors.initials: K
authors.lastname: Ando
authors.forename: Ke Ih
authors.initials: KI
authors.lastname: Kim
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Yano
authors.forename: Soo Ki
authors.initials: SK
authors.lastname: Kim
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: Aya
authors.initials: A
authors.lastname: Fujinami
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Ohta
authors.forename: Hatae
authors.initials: H
authors.lastname: Takashi
authors.forename: Hak
authors.initials: H
authors.lastname: Hotta
authors.forename: Yoshitake
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kudo
mesh_terms: D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000187:drug effects*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D007372:Interferons / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011092:Polyethylene Glycols / Q000737:chemistry*; D012254:Ribavirin / Q000494:pharmacology* / Q000627:therapeutic use*; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D011092:Polyethylene Glycols; D012254:Ribavirin; D007372:Interferons