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NS5A-P32 deletion as a factor involved in virologic failure in patients receiving glecaprevir and pibrentasvir

  • Hayato Uemura
  • Yoshihito Uchida
  • Jun-ichi Kouyama
  • Kayoko Naiki
  • Shohei Tsuji
  • Kayoko Sugawara
  • Masamitsu Nakao
  • Daisuke Motoya
  • Nobuaki Nakayama
  • Yukinori Imai
  • Tomoaki Tomiya
  • Satoshi Mochida
Original Article—Liver, Pancreas, and Biliary Tract

Abstract

Background

This study sought to clarify the factors involved in virologic failure in patients with HCV receiving retreatment with glecaprevir/pibrentasvir (GLE/PIB) in real-world practice.

Methods

Forty-two patients who had previously received direct-acting antivirals (DAAs) therapies consisting of 35, 3, 3, and 1 patient(s) with genotype (GT)-1b, GT-2a, GT-2b, and GT-3b HCV, respectively, received GLE/PIB for 12 weeks. Resistance-associated substitutions (RASs) at baseline were evaluated, and the dynamics of NS5A-RASs were assessed by deep sequencing in patients showing virologic failure.

Results

Baseline NS5A-RASs were found in all the patients with GT-1b HCV including 16 patients with NS3-RASs. In contrast, both NS5A-RASs and NS3-RASs were absent in 3 and 2 patients with GT-2a and GT-2b HCV, respectively. Virologic failure occurred in 3 patients with GT-1b HCV with NS5A-P32del, while a sustained virologic response (SVR) was achieved in the remaining 39 patients including those with GT-1b HCV carrying NS5A-L31V + Y93H and NS5A-A92K. Virologic failure even occurred in a patient in whom the NS5A-P32del HCV strains had become undetectable by direct sequencing, and the percentage of such strains relative to the total HCV strains was 10%, as determined by deep sequencing. In the other patient with GT-1b HCV with NS5A-P32del, NS3-A156A/V/S were found at 4 weeks after GLE/PIB therapy, but had disappeared at 11 weeks, as determined by direct sequencing.

Conclusions

GLE/PIB was effective for patients with HCV who failed to achieve an SVR after prior DAA therapies except in those with GT-1b HCV carrying NS5A-P32del even when such strains became undetectable by direct sequencing.

Keywords

NS5A-P32 deletion DAA retreatment Glecaprevir Pibrentasvir 

Notes

Acknowledgements

Satoshi MOCHIDA has received patent royalties from SRL Inc., has received speaking fees or honoraria from AbbVie GK, Ajinomoto Pharmaceuticals Co. Ltd., Bristol Myers Squibb Co., Gilead Sciences Inc., MSD K.K., Sumitomo Dainippon Pharma Co., Toray Medical Co. Ltd., has received research Grants from A2 Healthcare Co., AbbVie GK, Bristol Myers Squibb Co., Chugai Pharmaceutical Co. Ltd., EA Pharma Co. Ltd., Mitsubishi Tanabe Pharma Co., MSD K.K., Sumitomo Dainippon Pharma Co., Toray Medical Co. Ltd.

Yoshihito UCHIDA has received research Grant from AbbVie GK.

Funding

This study was supported by Research Program on Hepatitis from Japan Agency for Medical Research and Development (AMED): (Grant Number 18fk0210002h0003).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

535_2018_1543_MOESM1_ESM.docx (21 kb)
Supplementary material 1 (DOCX 20 kb)

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Copyright information

© Japanese Society of Gastroenterology 2019

Authors and Affiliations

  • Hayato Uemura
    • 1
  • Yoshihito Uchida
    • 1
  • Jun-ichi Kouyama
    • 1
  • Kayoko Naiki
    • 1
  • Shohei Tsuji
    • 1
  • Kayoko Sugawara
    • 1
  • Masamitsu Nakao
    • 1
  • Daisuke Motoya
    • 1
  • Nobuaki Nakayama
    • 1
  • Yukinori Imai
    • 1
  • Tomoaki Tomiya
    • 1
  • Satoshi Mochida
    • 1
  1. 1.Department of Gastroenterology & Hepatology, Faculty of MedicineSaitama Medical UniversityIruma-GunJapan

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