title: Reducing Peg-IFN doses causes later virologic response or no response in HCV genotype 1 patients treated with Peg-IFN alfa-2b plus ribavirin.
abstract: BACKGROUND
  The timing to the first undetectable hepatitis C virus (HCV) RNA level is strongly associated with sustained virologic response in pegylated interferon (Peg-IFN) plus ribavirin combination therapy for patients with chronic hepatitis C (CH-C) with genotype 1. This study was conducted to clarify the impact of drug exposure to Peg-IFN on the timing of HCV RNA negativity in Peg-IFN plus ribavirin combination therapy for CH-C patients with genotype 1.
  
  
  METHODS
  A total of 1409 patients treated with Peg-IFN alfa-2b plus ribavirin were enrolled and classified into four categories according to the Peg-IFN dosage. Furthermore, 100 patients were extracted from each Peg-IFN dosage category to adjust for characteristic factors, using the propensity score method.
  
  
  RESULTS
  Peg-IFN exposure was dose-dependently associated with the timing of HCV RNA negativity (p ≤ 0.001). The HCV RNA negative rate at week 4 decreased from 12% with a Peg-IFN dose of >1.5 μg/kg/week to 1-3% with a dose of <1.5 μg/kg/week (p ≤ 0.001), and at week 12 the rate had decreased from 44% with a dose of ≥1.2 μg/kg/week to 18% with a dose of <1.2 μg/kg/week (p = 0.001). Treatment failure (patients without a 1-log decrease of HCV RNA at week 4 or a 2-log decrease of HCV RNA at week 12, or positive at week 24) was found in 54-66% of patients given <1.2 μg/kg/week (p ≤ 0.001), and these patients accounted for 64% of the non-responders.
  
  
  CONCLUSIONS
  The timing of HCV RNA negativity depends significantly on the Peg-IFN dose. Reducing the Peg-IFN dose can induce a later virologic response or non-response in HCV genotype 1 patients treated with Peg-IFN plus ribavirin.
authors: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan.
authors: Tsugiko
authors: T
authors: Oze
authors: Naoki
authors: N
authors: Hiramatsu
authors: Changho
authors: C
authors: Song
authors: Takayuki
authors: T
authors: Yakushijin
authors: Sadaharu
authors: S
authors: Iio
authors: Yoshinobu
authors: Y
authors: Doi
authors: Masahide
authors: M
authors: Oshita
authors: Hideki
authors: H
authors: Hagiwara
authors: Eiji
authors: E
authors: Mita
authors: Toshifumi
authors: T
authors: Ito
authors: Yoshiaki
authors: Y
authors: Inui
authors: Taizo
authors: T
authors: Hijioka
authors: Shinji
authors: S
authors: Tamura
authors: Harumasa
authors: H
authors: Yoshihara
authors: Atsuo
authors: A
authors: Inoue
authors: Yasuharu
authors: Y
authors: Imai
authors: Eijiro
authors: E
authors: Hayashi
authors: Michio
authors: M
authors: Kato
authors: Masanori
authors: M
authors: Miyazaki
authors: Atsushi
authors: A
authors: Hosui
authors: Takuya
authors: T
authors: Miyagi
authors: Yuichi
authors: Y
authors: Yoshida
authors: Tomohide
authors: T
authors: Tatsumi
authors: Shinichi
authors: S
authors: Kiso
authors: Tatsuya
authors: T
authors: Kanto
authors: Akinori
authors: A
authors: Kasahara
authors: Norio
authors: N
authors: Hayashi
authors: Tetsuo
authors: T
authors: Takehara
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use*; D057216:Propensity Score; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012189:Retrospective Studies; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use*; D013997:Time Factors; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b