Real-world efficacy of glecaprevir plus pibrentasvir for chronic hepatitis C patient with previous direct-acting antiviral therapy failures

Abstract

Background

Combination therapy with glecaprevir (GLE) and pibrentasvir (PIB) has high efficacy for pan-genotypic hepatitis C virus (HCV)-infected patients. However, the efficacy of the therapy for failures to prior direct-acting antiviral (DAA) regimens in real-world practice is not well known.

Methods

Thirty patients infected with HCV genotype 1b, 2a, 2b, or 3a who failed to respond during prior DAA therapies were treated with GLE/PIB for 12 weeks. HCV NS3 and NS5A drug resistance-associated variants (RAVs) were determined by direct sequencing.

Results

Twenty-eight out of 30 patients (93.3%) achieved SVR12 by GLE/PIB treatment. SVR12 rates were similar between patients with and without advanced liver fibrosis (94.7% and 91.0%, respectively). All 9 patients with genotype 2a, 2b, or 3a HCV infection achieved SVR12. However, two genotype 1b HCV-infected patients who failed previous daclatasvir plus asunaprevir treatment experienced HCV relapse after the end of GLE/PIB treatment. Direct sequence analysis showed the presence of NS3-D168E plus NS5A-L31I/P58S/Y93H RAVs in one patient and NS5A-L31F/P32del RAVs in another patient before GLE/PIB treatment. In the former patient, NS3-D168E plus NS5A-L31I/P58S/Y93H RAVs persisted, and additional NS5A-L28M/V75A variants emerged after HCV relapse.

Conclusions

GLE/PIB treatment for HCV-infected patients who did not respond to prior DAA treatments was highly effective regardless of liver fibrosis stage. However, some genotype 1b HCV-infected patients, especially those with NS5A-P32del, may have low susceptibility to the treatment.

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Abbreviations

ASV:

Asunaprevir

BEC:

Beclabuvir

DAA:

Direct-acting antiviral

DCV:

Daclatasvir

GLE:

Glecaprevir

HCV:

Hepatitis C virus

LDV:

Ledipasvir

PIB:

Pibrentasvir

P32del:

P32 deletion

RAV:

Resistance-associated variant

RBV:

Ribavirin

SOF:

Sofosbuvir

SVR:

Sustained virological response

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Acknowledgments

The authors thank Nobuko Yokoyama, Emi Nishio and Akemi Sata for clerical assistance. This research is partially supported by research funding from the Research Program on Hepatitis from the Japan Agency for Medical Research and Development, AMED (Grant number: 17fk0210104h0001). This study was performed at Hiroshima University and hospitals belonging to the Hiroshima Liver Study Group.

Members of the Hiroshima Liver Study Group include Shiomi Aimitsu (Matsuishi Hospital), Takahiro Azakami (Hiroshima Memorial Hospital), Koji Kamada (Shobara Red Cross Hospital), Yoshio Katamura (Onomichi General Hospital), Hiroiku Kawakami and Yoshiiku Kawakami (Kawakami Clinic), Takashi Kimura (Kimura Clinic), Shoichi Takahashi (Koyo New Town Hospital), Keiji Tsuji, Shintaro Takaki and Nami Mori (Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital), Yuko Nagaoki (Mazda Hospital), Takashi Moriya (Chugoku Rosai Hospital) and Shuji Yamaguchi (Kure mutual aid Hospital).

Funding

The study was supported in part by research funding from the Research Program on Hepatitis from the Japan Agency for Medical Research and Development, AMED (Grant number: 17fk0210104h0001). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. There was no additional external funding received for this study.

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Correspondence to Kazuaki Chayama.

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Conflict of interest

Kazuaki Chayama has received honoraria from Bristol-Myers Squibb and MSD K.K. and research funding from Dainippon Sumitomo Pharma and AbbVie. Michio Imamura has received research funding from Bristol-Myers Squibb.

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Members of Hiroshima Liver Study Group are listed in acknowledgments.

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Osawa, M., Imamura, M., Teraoka, Y. et al. Real-world efficacy of glecaprevir plus pibrentasvir for chronic hepatitis C patient with previous direct-acting antiviral therapy failures. J Gastroenterol 54, 291–296 (2019). https://doi.org/10.1007/s00535-018-1520-9

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Keywords

  • Glecaprevir
  • Pibrentasvir
  • NS5A RAVs
  • NS5A-P32 deletion