α-Fetoprotein is a surrogate marker for predicting treatment failure in telaprevir-based triple combination therapy for genotype 1b chronic hepatitis C Japanese patients with the IL28B minor genotype

J Med Virol. 2014 Mar;86(3):461-72. doi: 10.1002/jmv.23824. Epub 2013 Oct 28.

Abstract

Even when treated with telaprevir-based triple therapy, some patients fail to achieve a sustained virological response. This study identified factors related closely to treatment failure. A total of 146 Japanese genotype 1b chronic hepatitis C patients were enrolled in this prospective, multicenter study and received a 24-week regimen of triple therapy. The end-of-treatment response rate was significantly lower in patients with the interleukin 28B (IL28B) (rs8099917) non-TT genotype (85.2%) than in those with the TT genotype (100%, P = 0.0002). Multiple logistic regression analysis identified high α-fetoprotein levels as an independent factor related to non-end-of-treatment response in patients with the non-TT genotype. A cut-off value of 20 ng/ml was determined for a non-end-of-treatment response; sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were 75.0%, 95.7%, 75.0%, 75.0%, and 92.6%, respectively. Multiple logistic regression analysis for a sustained virological response identified the IL28B TT genotype, low α-fetoprotein levels, non-responders, and a rapid virological response. The sustained virological response rate was significantly lower in patients with the non-TT genotype (59.3%) than in those with the TT genotype (96.7%, P < 0.0001). In patients with the non-TT genotype, α-fetoprotein was the most significant predictor for non-sustained virological response by univariate analysis. A cut-off value of 7.4 ng/ml α-fetoprotein was determined for non-sustained virological response; sensitivity, specificity, PPV, NPV, and accuracy were 63.6%, 87.5%, 77.8%, 77.8%, and 77.8%, respectively. For the non-TT patients, serum α-fetoprotein levels may be a surrogate marker for predicting treatment failure in telaprevir-based therapy for genotype 1b chronic hepatitis C.

Keywords: HCV; IL28B; telaprevir; α-fetoprotein.

Publication types

  • Evaluation Study
  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antiviral Agents / therapeutic use*
  • Asian People
  • Biomarkers / blood
  • Drug Monitoring / methods*
  • Drug Therapy, Combination / methods
  • Genotype
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Interferons
  • Interleukins / genetics*
  • Middle Aged
  • Oligopeptides / therapeutic use*
  • Predictive Value of Tests
  • Prospective Studies
  • Sensitivity and Specificity
  • Treatment Failure
  • Young Adult
  • alpha-Fetoproteins / analysis*

Substances

  • Antiviral Agents
  • Biomarkers
  • interferon-lambda, human
  • Interleukins
  • Oligopeptides
  • alpha-Fetoproteins
  • telaprevir
  • Interferons