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

J Gastroenterol Hepatol. 2014 Jan;29(1):201-7. doi: 10.1111/jgh.12376.

Abstract

Background and aim: 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.

Keywords: HCV; ITPA genotype; extended therapy; treatment outcome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / administration & dosage*
  • Drug Therapy, Combination
  • Female
  • Genotype*
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / genetics*
  • Hepatitis C, Chronic / virology
  • Humans
  • Inosine Triphosphatase
  • Inosine Triphosphate / genetics*
  • Interferon alpha-2
  • Interferon-alpha / administration & dosage*
  • Interferon-alpha / pharmacokinetics
  • Interferons
  • Interleukins / genetics
  • Male
  • Middle Aged
  • Polyethylene Glycols / administration & dosage*
  • Polyethylene Glycols / pharmacokinetics
  • Polymorphism, Single Nucleotide*
  • Pyrophosphatases / genetics
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / pharmacokinetics
  • Regression Analysis
  • Ribavirin / administration & dosage*
  • Ribavirin / pharmacokinetics
  • Time Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Antiviral Agents
  • interferon-lambda, human
  • Interferon alpha-2
  • Interferon-alpha
  • Interleukins
  • Recombinant Proteins
  • Inosine Triphosphate
  • Polyethylene Glycols
  • Ribavirin
  • Interferons
  • Pyrophosphatases
  • peginterferon alfa-2b
  • peginterferon alfa-2a