title: Using early viral kinetics to predict antiviral outcome in response-guided pegylated interferon plus ribavirin therapy among patients with hepatitis C virus genotype 1.
abstract: BACKGROUND
  HCV kinetics during treatment demonstrated strong association with the antiviral outcome of patients treated with pegylated interferon (Peg-IFN) plus ribavirin. However, the relationship between HCV kinetics and pre-treatment factors remains unclear.
  
  
  METHODS
  Of 547 patients with HCV genotype 1 treated with Peg-IFN alfa-2b plus ribavirin, 401 completed the response-guided therapy and were assessed for per protocol analysis.
  
  
  RESULTS
  The sustained virologic response (SVR) rate was 53 % for all patients, 60 % for those with genotype TT, and 19 % for those with genotype TG/GG according to IL28B (rs8099917) single nucleotide polymorphisms. The SVR rates increased with HCV decrease at week 4; 4 % (2/56) with <1 log10 decrease, 13 % (7/56) with 1-2 log10 decrease, 51 % (44/87) with 2-3 log10 decrease, 64 % (56/87) with 3-4 log10 decrease, 88 % (72/82) with more than 4 log10 decrease but with detectable HCV RNA and 100 % (33/33) with undetectable HCV RNA (p < 0.001). Similarly, SVR rates increased step-by-step in proportion to HCV decrease in both IL28B TT and TG/GG groups, showing almost the same SVR rates for the same conditions. In multivariate analysis, age (p = 0.005) and the magnitude of HCV decrease at week 4 (p < 0.001) but not IL28B were associated with SVR. Advanced liver fibrosis (p = 0.004) and the magnitude of HCV decrease at week 4 (p < 0.001) but not IL28B were associated with non-response.
  
  
  CONCLUSIONS
  The magnitude of the HCV decrease at week 4 seems to be the most reliable marker for predicting antiviral outcome after starting Peg-IFN plus ribavirin therapy.
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Tsugiko
authors.initials: T
authors.lastname: Oze
authors.forename: Naoki
authors.initials: N
authors.lastname: Hiramatsu
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yakushijin
authors.forename: Masanori
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Sadaharu
authors.initials: S
authors.lastname: Iio
authors.forename: Masahide
authors.initials: M
authors.lastname: Oshita
authors.forename: Hideki
authors.initials: H
authors.lastname: Hagiwara
authors.forename: Eiji
authors.initials: E
authors.lastname: Mita
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Inui
authors.forename: Taizo
authors.initials: T
authors.lastname: Hijioka
authors.forename: Masami
authors.initials: M
authors.lastname: Inada
authors.forename: Shinji
authors.initials: S
authors.lastname: Tamura
authors.forename: Harumasa
authors.initials: H
authors.lastname: Yoshihara
authors.forename: Atsuo
authors.initials: A
authors.lastname: Inoue
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Imai
authors.forename: Takuya
authors.initials: T
authors.lastname: Miyagi
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Tomohide
authors.initials: T
authors.lastname: Tatsumi
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kanto
authors.forename: Akinori
authors.initials: A
authors.lastname: Kasahara
authors.forename: Norio
authors.initials: N
authors.lastname: Hayashi
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Takehara
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics; D008103:Liver Cirrhosis / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D012367:RNA, Viral / Q000097:blood*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use*; D013997:Time Factors; D019562:Viral Load; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D012367:RNA, Viral; D011994:Recombinant Proteins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C417083:peginterferon alfa-2b