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©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
Importance of virological response in the early stage of telaprevir-based triple therapy for hepatitis C
Satoshi Hiramine, Norihiro Furusyo, Eiichi Ogawa, Makoto Nakamuta, Eiji Kajiwara, Hideyuki Nomura, Kazufumi Dohmen, Kazuhiro Takahashi, Takeaki Satoh, Koichi Azuma, Akira Kawano, Toshimasa Koyanagi, Kazuhiro Kotoh, Shinji Shimoda, Jun Hayashi
Satoshi Hiramine, Norihiro Furusyo, Eiichi Ogawa, Department of General Internal Medicine, Kyushu University Hospital, Fukuoka 812-8582, Japan
Makoto Nakamuta, Department of Gastroenterology, Kyushu Medical Center, National Hospital Organization, Fukuoka 810-8563, Japan
Eiji Kajiwara, Department of Hepatology, Steel Memorial Yahata Hospital, Kitakyushu 805-0050, Japan
Hideyuki Nomura, the Center for Liver Disease, Shin-Kokura Hospital, Kitakyushu 803-0816, Japan
Kazufumi Dohmen, Department of Internal Medicine, Chihaya Hospital, Fukuoka 813-0044, Japan
Kazuhiro Takahashi, Department of Medicine, Hamanomachi Hospital, Fukuoka 810-8539, Japan
Takeaki Satoh, Center for Liver Disease, National Hospital Organization Kokura Medical Center, Kitakyushu 802-0803, Japan
Koichi Azuma, Department of Medicine, Kyushu Central Hospital, Fukuoka 815-0032, Japan
Akira Kawano, Department of Medicine, Kitakyushu Municipal Medical Center, Kitakyushu 802-0077, Japan
Toshimasa Koyanagi, Department of Medicine, Fukuoka City Hospital, Fukuoka 812-0046, Japan
Kazuhiro Kotoh, Shinji Shimoda, Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
Jun Hayashi, Kyushu General Internal Medicine Center, Hara-Doi Hospital, Fukuoka 813-8588, Japan
Author contributions: Hiramine S, Furusyo N and Ogawa E designed and contributed to the conception of the study; Ogawa E, Nakamuta M, Kajiwara E, Nomura H, Dohmen K, Takahashi K, Satoh T, Azuma K, Kawano A, Kotoh K, Shimoda S and Hayashi J contributed to data acquisition; Hiramine S and Ogawa E analyzed and interpreted data; Hiramine S, Furusyo N, Ogawa E, Koyanagi T and Hayashi J contributed to the drafting of the paper and its revision and are responsible for the intellectual content.
Conflict-of-interest statement: Norihiro Furusyo has received an investigator initiated study research grant from Janssen Pharmaceutical K.K. He has also received research funding from Mitsubishi Tanabe Pharma Co., MSD K.K., Chugai Co., Daiichi Sankyo Co., and Bristol-Myers K.K. The remaining authors have no conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Jun Hayashi, MD, PhD, Kyushu General Internal Medicine Center, Hara-Doi Hospital, 6-40-8 Aoba, Higashi-ku, Fukuoka 813-8588, Japan.
hayashij@gim.med.kyushu-u.ac.jp
Telephone: +81-92-6913881 Fax: +81-92-6911059
Received: February 27, 2015
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.
