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©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
Real-world efficacy of daclatasvir and asunaprevir with respect to resistance-associated substitutions
Hideki Fujii, Atsushi Umemura, Taichiro Nishikawa, Kanji Yamaguchi, Michihisa Moriguchi, Hideki Nakamura, Kohichiroh Yasui, Masahito Minami, Saiyu Tanaka, Hiroki Ishikawa, Hiroyuki Kimura, Shiro Takami, Yasuyuki Nagao, Toshihide Shima, Yoshito Itoh
Hideki Fujii, Hiroyuki Kimura, Department of Gastroenterology, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto 6050981, Japan
Hideki Nakamura, Department of Gastroenterology and Hepatology, North Medical Center, Kyoto Prefectural University of Medicine, Kyoto 6292261, Japan
Masahito Minami, Department of Internal Medicine, Aiseikai Yamashina Hospital, Kyoto 6078086, Japan
Saiyu Tanaka, Center for Digestive and Liver Diseases, Nara City Hospital, Nara 6308305, Japan
Hiroki Ishikawa, Department of Gastroenterology and Hepatology, Omihachiman Community Medical Center, Shiga 5230082, Japan
Shiro Takami, Department of Gastroenterology, Otsu Municipal Hospital, Otsu 5200804, Japan
Yasuyuki Nagao, Department of Gastroenterology, Matsushita Memorial Hospital, Moriguchi 5708540, Japan
Toshihide Shima, Center of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Suita 5640013, Japan
Author contributions: Fujii H and Itoh Y designed the research and wrote the paper; Umemura A, Nishikawa T, Yamaguchi K, Moriguchi M, Nakamura H, Minami M, Yasui K, Kimura H, Tanaka S, Ishikawa H, Takami S, Nagao Y and Shima T collected the data and samples.
Institutional review board statement: This study was reviewed and approved by the Kyoto Prefectural University and seven affiliated hospitals of the Medicine Institutional Review Board (IRB).
Informed consent statement: All study participants provided informed written consent before study enrollment.
Conflict-of-interest statement: Yoshito Itoh receives lecture fees from Merck Sharp and Dohme, Gilead Sciences Inc., AbbVie GK, and Bristol-Myers Squibb Company. Yoshito Itoh receives research grants from AbbVie GK, Gilead Sciences Inc., Merck Sharp and Dohme, and Bristol-Myers Squibb Company.
Data sharing statement: No additional data are available. Responses to the request for raw data will be judged by the IRB.
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: Hideki Fujii, MD, PhD, Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajiichou, Kamigyouku, Kyoto 6028566, Japan. fuhideki@koto.kpu-m.ac.jp
Telephone: +81-75-2515519 Fax: +81-75-2510710
Received: March 16, 2017
Peer-review started: March 17, 2017
First decision: May 3, 2017
Revised: May 17, 2017
Accepted: July 14, 2017
Article in press: July 17, 2017
Published online: September 8, 2017
AIM
To investigate daclatasvir (DCV) and asunaprevir (ASV) efficacy in hepatitis C (HCV) patients, with respect to resistance-associated substitutions (RASs).
METHODS
A total of 392 HCV-infected patients from multiple centers were included in this study. We evaluated their clinical courses and sustained virologic responses (SVR) according to pretreatment factors (gender, age, history of interferon-based regimens, platelet counts, level of viremia, pretreatment NA5A:L31, and Y93 substitutions). We also analyzed the pretreatment and post-treatment major RASs of NS3:D168, NS5A:L31 and Y93 substitutions using a direct-sequencing method in 17 patients who were unable to achieve SVR at 12 wk after treatment completion (SVR12).
RESULTS
The overall SVR12 rate was 88.3%. Thirty-one patients discontinued treatment before 24 wk because of adverse events, 23 of whom achieved SVR12. There were no significant differences in SVR12 rates with respect to gender, age, history of interferon-based regimens, and platelet counts. The SVR12 rate in patients with viral loads of ≥ 6.0 log IU/mL was significantly lower than those with viral loads of < 6.0 log IU/mL (P < 0.001). The SVR12 rate in patients with Y93 substitution-positive was significantly lower than those with Y93 substitution-negative (P < 0.001). The L31 substitution-positive group showed a lower SVR12 rate than the L31 substitution-negative group, but the difference was not statistically significant. Seventeen patients who did not achieve SVR12 and had available pretreatment and post-treatment sera had additional RASs in NS3:D168, NS5:L31, and Y93 substitution at treatment failure.
CONCLUSION
Combination of DCV and ASV is associated with a high SVR rate. Baseline RASs should be thoroughly assessed to avoid additional RASs after treatment failure.
Core tip: Hepatitis C - infected patients treated with daclatasvir and asunaprevir were evaluated for sustained virological response (SVR) according to pretreatment factors. The overall rate of SVR12 was 88.3%. The SVR12 rate in the ≥ 6.0 log IU/mL group was significantly lower than in the < 6.0 log IU/mL group. The SVR12 rate in Y93 substitution-positive patients was significantly lower than that in non-Y93 substitution patients. The L31 substitution-positive group had a lower SVR 12 rate than the L31 substitution-negative group. Seventeen patients who did not achieve SVR 12 had additional RASs in NS3:D168, NS5:L31, and Y93 post-treatment. Baseline RASs should be thoroughly assessed to avoid additional RASs after treatment failure.
