title: Relationship between inosine triphosphate genotype and outcome of extended therapy in hepatitis C virus patients with a late viral response to pegylated-interferon and ribavirin.
abstract: OBJECTIVE
  It is not yet clear which factors are associated with the outcome of 72-week treatment with pegylated-interferon and ribavirin (RBV) in patients with chronic hepatitis C virus (HCV) infection.
  
  
  METHODS
  In 66 patients with HCV genotype 1 who had a late viral response (LVR) to 72-week treatment of pegylated-interferon and RBV, we examined the factors that determined the outcome, including single nucleotide polymorphisms of interleukin-28B and inosine triphosphatase (ITPA) genes.
  
  
  RESULTS
  Thirty seven of 66 (56%) patients with LVR achieved a sustained viral response (SVR). The mean age of these 37 SVR patients was 55, compared with 61 in 29 relapsed patients (P = 0.009). Twenty six of 54 (48%) patients with the CC genotype and 11 of 12 (92%) with the CA/AA genotype of ITPA rs1127354 achieved SVR (P = 0.006). The SVR rates were 79%, 40%, 60%, and 33% in patients with undetectable HCV RNA on weeks 16, 20, 24, and 28 or later, respectively (P = 0.014). Finally, serum RBV concentration at week 44 of treatment was significantly higher in the SVR group (2651 ng/mL) than in the relapse group (1989 ng/mL, P = 0.002). In contrast, the rate of the interleukin-28B genotype was not different between the groups. Multiple regression analysis showed that age < 60 years, ITPA CA/AA genotype, and serum RBV concentration were significant independent predictive factors for SVR.
  
  
  CONCLUSIONS
  Our findings elucidated the association of four factors, including ITPA genotype, with the outcome of 72-week treatment in LVR patients.
authors: Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors: Hoang
authors: H
authors: Hai
authors: Akihiro
authors: A
authors: Tamori
authors: Masaru
authors: M
authors: Enomoto
authors: Hiroyasu
authors: H
authors: Morikawa
authors: Sawako
authors: S
authors: Uchida-Kobayashi
authors: Hideki
authors: H
authors: Fujii
authors: Atsushi
authors: A
authors: Hagihara
authors: Etsushi
authors: E
authors: Kawamura
authors: Le Thi Thanh
authors: le TT
authors: Thuy
authors: Yasuhito
authors: Y
authors: Tanaka
authors: Norifumi
authors: N
authors: Kawada
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics* / Q000821:virology; D006801:Humans; D007293:Inosine Triphosphate / Q000235:genetics*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007372:Interferons; D007378:Interleukins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000493:pharmacokinetics; D020641:Polymorphism, Single Nucleotide; D011755:Pyrophosphatases / Q000235:genetics; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics; D012044:Regression Analysis; D012254:Ribavirin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult; D000097630:Inosine Triphosphatase; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D007293:Inosine Triphosphate; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D011755:Pyrophosphatases; D011994:Recombinant Proteins; D012254:Ribavirin; D000097630:Inosine Triphosphatase; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a
keywords: HCV; ITPA genotype; extended therapy; treatment outcome