Baseline factors and very early viral response (week 1) for predicting sustained virological response in telaprevir-based triple combination therapy for Japanese genotype 1b chronic hepatitis C patients: a multicenter study

J Gastroenterol. 2014 Nov;49(11):1485-94. doi: 10.1007/s00535-013-0918-7. Epub 2013 Nov 28.

Abstract

Background: Genetic polymorphisms near Interleukin 28B (IL28B) (rs8099917) and a rapid virological response (RVR) have been reported as predictors for a sustained virological response (SVR) to telaprevir (TVR)-based triple combination therapy. However, the association between SVR and viral kinetics earlier than week 4 after initiation of therapy remains unclear. Thus, we evaluated the SVR prediction ability of baseline factors and reduced hepatitis C virus (HCV) RNA levels at week 1 after the initiation of TVR-based therapy in Japanese genotype-1b chronic hepatitis C (CHC) patients.

Methods: A total of 156 Japanese CHC patients received a 24-week regimen of TVR-based therapy. Baseline factors and reduction in HCV RNA levels at weeks 1 and 4 after the initiation of therapy were analyzed for SVR prediction.

Results: Multiple logistic regression analysis for SVR in TVR-based therapy identified the IL28B TT genotype, a reduction of ≥ 4.7 log10 IU/mL in HCV RNA levels at week 1, RVR, and treatment-naïve/relapse. Whereas the SVR rate was higher than 90 % regardless of the reduction in HCV RNA levels at week 1 in patients with the TT genotype, a reduction of ≥ 4.7 log10 IU/mL in HCV RNA levels at week 1 was the strongest predictor of SVR in patients with the non-TT genotype, as determined by multiple logistic regression analysis (P = 0.0043).

Conclusions: The IL28B TT genotype is the most important baseline factor for predicting SVR, and a ≥ 4.7 log10 IU/mL reduction in HCV RNA at week 1 is a useful very early on-treatment predictor of SVR, especially in the non-TT genotype.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antiviral Agents / therapeutic use*
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Genetic Markers
  • Genotype*
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / genetics
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use
  • Interferons
  • Interleukins / genetics*
  • Japan
  • Logistic Models
  • Male
  • Middle Aged
  • Oligopeptides / therapeutic use*
  • Polyethylene Glycols / therapeutic use
  • Polymorphism, Single Nucleotide*
  • Prospective Studies
  • Recombinant Proteins / therapeutic use
  • Ribavirin / therapeutic use
  • Treatment Outcome
  • Young Adult

Substances

  • Antiviral Agents
  • Genetic Markers
  • interferon-lambda, human
  • Interferon alpha-2
  • Interferon-alpha
  • Interleukins
  • Oligopeptides
  • Recombinant Proteins
  • Polyethylene Glycols
  • Ribavirin
  • telaprevir
  • Interferons
  • peginterferon alfa-2b