Retrospective Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Jan 27, 2018; 10(1): 88-94
Published online Jan 27, 2018. doi: 10.4254/wjh.v10.i1.88
Efficacy of direct-acting antiviral treatment for chronic hepatitis C: A single hospital experience
Rena Kaneko, Natsuko Nakazaki, Risa Omori, Yuichiro Yano, Masazumi Ogawa, Yuzuru Sato
Rena Kaneko, Natsuko Nakazaki, Risa Omori, Yuichiro Yano, Masazumi Ogawa, Yuzuru Sato, Department of Gastroenterology, Japan Organization of Occupational Health and Safety Kanto Rosai Hospital, Nakahara Kawasaki City, Kanagawa 211-8510, Japan
Author contributions: Kaneko R collected and analyzed the data, and drafted the manuscript; Nakazaki N, Omori R and Yano Y contributed the clinical study; Ogawa M and Sato Y supervised the study; all authors have read and approved the final version to be published.
Supported by research funds to promote the Hospital functions of the Japan Organization of Occupational Health and Safety; No. 359.
Institutional review board statement: This study was reviewed and approved by the Kanto Rosai Hospital Review Board.
Informed consent statement: Written informed consent was obtained from the patient for this study.
Conflict-of-interest statement: The authors declare no potential conflict of interest.
Data sharing statement: Participants gave informed consent for data sharing.
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: Rena Kaneko, MD, Department of Gastroenterology, Japan Organization of Occupational Health and Safety Kanto Rosai Hospital, Kizukisumiyoshi-cho 1-1, Nakahara-ku, Kawasaki City, Kanagawa 211-8510, Japan. rena@kantoh.johas.go.jp
Telephone: +81-44-4113131 Fax: +81-44-4113150
Received: September 27, 2017
Peer-review started: October 2, 2017
First decision: November 27, 2017
Revised: December 6, 2017
Accepted: December 13, 2017
Article in press: December 13, 2017
Published online: January 27, 2018
Processing time: 120 Days and 22.3 Hours
ARTICLE HIGHLIGHTS
Research background

In a previous study, it was shown that resistance-associated substitutions (RASs) were predictors of direct-acting antiviral (DAA) failure. No significant adverse effect was reported in the DAA treatment in clinical trials. In this study, the prestudy hypothesis was that another predictor might exist concerning about DAA failure. Another hypothesis was that more severe adverse effects must occur in the real world because patients conditions were more severe than those of clinical trials.

Research motivation

DAAs have been approved for the treatment of hepatitis C virus (HCV) genotype 1 and 2 infections in Japan since 2011. In the new era of DAA therapy, predictors who fail to respond to DAA might be compromised by RASs. There have been few reports of daclatasvir/asunaprevir (DCV/ASV) failure because DCV/ASV is limited in Japan. Therefore, it might be important to report these cases for future research and treatment of HCV.

Research objectives

All patients with HCV infection who underwent DAA prescription were enrolled in this study. Overall, 177 participants treated with DAAs and in whom sustained virologic response at 12 wk after therapy (SVR12) was judged between November 2012 and March 2017 at Kanto Rosai Hospital were included.

Research methods

HCV patients who underwent DAA prescription were enrolled in this study. Resistance analysis was performed by using direct sequencing and cycleave PCR. Multiple regression analysis was performed to evaluate factors related to loss of HCV RNA.

Research results

In total, 117 patients participated in the study, including 135 with genotype 1 and 42 with genotype 2. Of the 135 patients with genotype 1, 16 received protease inhibitor + interferon + ribavirin and all achieved SVR. Of the 119 patients who received interferon-free DAA (in different combinations), 102 achieved SVR while 9 failed, including 7/9 who were on DCV/ASV and 2/9 who were on ledipasvir/sofosbuvir. Efficacy analysis was done only for 42 patients who received DCV/ASV. From this analysis, Y93 RASs were significantly correlated with SVR.

Research conclusions

The SVR rate was 98% for genotype 1 and 100% for genotype 2. NS5A RASs are most likely to affect the outcomes of DAA therapy in our facility.

Research perspectives

The SVR rate was 98% for genotype 1 and 100% for genotype 2. However, caution is needed for HCV NS5A RASs that are selected by HCV NS5A inhibitors because cerebrovascular adverse events are induced by some DAA drugs.