Published online Nov 18, 2015. doi: 10.4254/wjh.v7.i26.2688
Peer-review started: March 1, 2015
First decision: April 13, 2015
Revised: May 3, 2015
Accepted: September 2, 2015
Article in press: September 7, 2015
Published online: November 18, 2015
Processing time: 263 Days and 14.5 Hours
AIM: To investigate the efficacy of virological response (VR) to telaprevir (TVR)-based triple therapy in predicting treatment outcome of hepatitis C.
METHODS: This prospective, multicenter study consisted of 253 Japanese patients infected with hepatitis C virus (HCV) genotype 1b. All received 12 wk of TVR in combination with 24 wk of pegylated-interferon-α (IFN-α) and ribavirin. Serum HCV RNA was tested at weeks 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24. VR was defined as undetectable serum HCV RNA. Sustained virological response (SVR) was VR at 24 wk after the end of treatment and was regarded as a successful outcome.
RESULTS: Of 253 patients, 207 (81.8%) achieved SVR. The positive predictive value of VR for SVR was 100% at week 2, after which it gradually decreased, and was over 85% to week 12. The negative predictive value (NPV) gradually increased, reaching 100% at week 12. The upslope of the NPV showed a large increase from week 4 (40.6%) to week 6 (82.4%). There was a moderate concordance between the SVR and VR at week 6 (kappa coefficient = 0.44), although other VRs had poor concordance to SVR. Multiple logistic regression analysis extracted VR at week 6 (P < 0.0001, OR = 63.8) as an independent factor contributing to SVR. In addition, the interleukin-28B single nucleotide polymorphism and response to previous pegylated-IFN-α and ribavirin therapy were identified as independent factors for SVR.
CONCLUSION: VR at week 6, but not at week 4, is an efficient predictor of both SVR and non-SVR to TVR-based triple therapy.
Core tip: Although an undetectable viral level at week 4 or 12 is a good predictor of the outcome of hepatitis C for conventional interferon therapy without direct-acting antiviral agents (DAAs); the transition of the viral level during DAA therapy has not been well documented. In this prospective multicenter study, we frequently tested 253 patients to investigate viral activity during triple therapy containing telaprevir, the first approved DAA, and found that an undetectable viral level at week 6 was the most effective predictor of disease outcome. Our findings suggest that the most predictive time point in DAA therapy is different from conventional therapy markers.