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
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.
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.
Multiple logistic regression analysis for SVR in TVR-based therapy identified the IL28B TT genotype, a reduction of ≥4.7 log10IU/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 log10IU/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).
The IL28B TT genotype is the most important baseline factor for predicting SVR, and a ≥4.7 log10IU/mL reduction in HCV RNA at week 1 is a useful very early on-treatment predictor of SVR, especially in the non-TT genotype.
KeywordsChronic hepatitis C Reduction in HCV RNA at week 1 Telaprevir IL28B
Conflict of interest
The authors declare that they have no conflict of interest.
- 1.Ghany MG, Nelson DR, Strader DB, American Association for Study of Liver Diseases, et al. An update on treatment of genotype 1 chronic hepatitis C virus infection: 2011 practice guideline by the American Association for the Study of Liver Diseases. Hepatology. 2011;54:1433–44.PubMedCentralPubMedCrossRefGoogle Scholar
- 15.Tsubota A, Shimada N, Atsukawa M, et al. Impact of IL28B polymorphisms on 24-week telaprevir-based combination therapy for Asian chronic hepatitis C patients with HCV genotype 1b. J Gastroenterol Hepatol. 2013 (Epub ahead of print).Google Scholar
- 16.Shimada N, Tsubota A, Atsukawa M, et al. 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. 2013 (Epub ahead of print).Google Scholar
- 21.Toyoda H, Kumada T, Shimada N, et al. Baseline factors and early viral response (week 4) to antiviral therapy with peginterferon and ribavirin for predicting sustained virologic response in patients infected with hepatitis C virus genotype 1: a multicenter study. J Med Virol. 2013;85:65–70.PubMedCrossRefGoogle Scholar
- 22.Toyoda H, Kumada T, Shimada N, et al. Significance of a reduction in HCV RNA levels at 4 and 12 weeks in patients infected with HCV genotype 1b for the prediction of the outcome of combination therapy with peginterferon and ribavirin. BMC Infect Dis. 2012;12:324.PubMedCentralPubMedCrossRefGoogle Scholar
- 33.Akuta N, Suzuki F, Kawamura Y, et al. Predictive factors of early and sustained responses to peginterferon plus ribavirin combination therapy in Japanese patients infected with hepatitis C virus genotype 1b: amino acid substitutions in the core region and low-density lipoprotein cholesterol levels. J Hepatol. 2007;46:403–10.PubMedCrossRefGoogle Scholar
- 36.Hayashi N, Seto C, Kato M, et al. Once-daily simeprevir (TMC435) with peginterferon/ribavirin for treatment-naïve hepatitis C genotype 1-infected patients in Japan: the DRAGON study. J Gastroenterol. 2013 (Epub ahead of print).Google Scholar