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Retreatment with sofosbuvir, ledipasvir, and add-on ribavirin for patients who failed daclatasvir and asunaprevir combination therapy

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
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Abstract

Background

The optimal retreatment regimen for patients with hepatitis C virus (HCV) infection who failed interferon-free, direct-acting antiviral (DAA) therapy is undetermined. In this study, we aimed to evaluate the efficacy and safety of 12-week retreatment with ledipasvir (LDV) and sofosbuvir (SOF) with add-on ribavirin (RBV) for patients who previously failed to respond to HCV-NS5A inhibitor, daclatasvir (DCV), and HCV-NS3 inhibitor, asunaprevir (ASV), therapy.

Methods

This multicenter, prospective study enrolled 15 patients with genotype-1 HCV infection who failed DCV/ASV combination therapy. They were retreated with SOF, LDV, and RBV for 12 weeks and underwent physical examinations and blood tests at baseline, during treatment, and after therapy. At baseline and relapse, NS3/NS5A and NS5B resistance-associated variants (RAVs) were evaluated.

Results

Of the 15 enrolled patients, 73.3% (11/15), 86.7% (13/15), and 0% (0/15) had RAVs in NS3 D168A/V/T/E, NS5A L31I/M/F/V plus Y93H, and NS5B S282T, respectively. Overall, 86.7% (13/15) of patients achieved a sustained viral response, and all patients completed therapy. No patients experienced severe adverse events. Two patients who failed to respond to SOF, LDV, and RBV combination therapy were elderly women, had the IL28B non-TT genotype, and NS5A RAVs in L31I/Y93H or NS5A A92 K at baseline.

Conclusions

This study revealed that SOF, LDV, and RBV combination therapy was effective and well-tolerated for patients with genotype-1 HCV infection who failed DCV and ASV combination therapy. Thus, RBV added to DAA therapy for difficult-to-treat patients might improve treatment outcomes.

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Abbreviations

DAAs:

Direct-acting antivirals

HCV:

Hepatitis C virus

PI:

Protease inhibitor

RAVs:

Resistance-associated variants

SVR:

Sustained virological response

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Acknowledgements

This study was supported in part by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan and the Japan Agency for Medical Research and development. The principal investigators of the NORTE study sites are listed below: Junichi Yoshida (JCHO Sapporo Hokushin Hospital), Akira Fuzinaga, (Abashiri-Kosei General Hospital), Keisuke Shinada (Keiwakai Ebetsu Hospital) Shuichi Muto (National Hospital Organization Hokkaido Medical Center), Takashi Meguro (Hokkaido Gastroenterology Hospital), Munenori Okamoto (Aiiku Hospital), Mineo Kudo (Sapporo Hokuyu Hospital), Nobuaki Akakura (NTT EAST Sapporo Hospital), Minoru Uebayashi (Japanese Red Cross Kitami Hospital), Kanji Katou (Iwamizawa Municipal General Hospital), Yasuyuki Kunieda (Wakkanai City Hospital), Miki Tateyama (Tomakomai Nissho Hospital), Atshuhiko Kawakami (Sapporo Century Hospital), and Izumi Tsunematsu (Touei hospital).

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Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan

    Goki Suda, Koji Ogawa, Megumi Kimura, Naoki Kawagishi, Masatsugu Ohara, Machiko Umemura, Jun Ito, Takaaki Izumi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa & Naoya Sakamoto

  2. Hakodate City General Hospital, Hakodate, Hokkaido, Japan

    Yoshiya Yamamoto

  3. Sapporo Hokuyu Hospital, Sapporo, Hokkaido, Japan

    Masaki Katagiri

  4. JCHO Hokkaido Hospital, Sapporo, Hokkaido, Japan

    Ken Furuya

  5. Mori City National Health Insurance Hospital, Mori, Hokkaido, Japan

    Kenichi Kumagai

  6. Hakodate Central General Hospital, Hakodate, Hokkaido, Japan

    Jun Konno

  7. Core Research Facilities for Basic Science, Division of Molecular Cell Biology, Research Center for Medical Science, The Jikei University School of Medicine, Tokyo, Japan

    Akihito Tsubota

  8. Division of Gastroenterology and Hepatology, Ootakanomori Hospital, Chiba, Japan

    Noritomo Shimada

  9. Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

    Etsuko Iio & Yasuhito Tanaka

Authors
  1. Goki Suda
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  2. Koji Ogawa
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  3. Yoshiya Yamamoto
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  4. Masaki Katagiri
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  5. Ken Furuya
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  6. Kenichi Kumagai
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  7. Jun Konno
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  8. Megumi Kimura
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  9. Naoki Kawagishi
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  10. Masatsugu Ohara
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  11. Machiko Umemura
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  12. Jun Ito
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  13. Takaaki Izumi
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  14. Masato Nakai
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  15. Takuya Sho
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  16. Mitsuteru Natsuizaka
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  17. Kenichi Morikawa
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  18. Akihito Tsubota
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  19. Noritomo Shimada
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  20. Etsuko Iio
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  21. Yasuhito Tanaka
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  22. Naoya Sakamoto
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Consortia

NORTE Study Group

Corresponding author

Correspondence to Naoya Sakamoto.

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Conflict of interest

N. Sakamoto received lecture fees from Bristol Myers Squibb and Pharmaceutical K.K., grants and endowments from MSD K.K. and Chugai Pharmaceutical Co., Ltd., and a research grant from Gilead Sciences, Inc. G. Suda received research grants from Bristol Myers Squibb and MSD K.K. Y. Tanaka received lecture fees from Bristol-Myers Squibb, MSD K.K., Chugai Pharmaceutical Co., Ltd., AbbVie Inc., Janssen Pharmaceutical K.K., Gilead Sciences, and a research grant from Bristol-Myers Squibb, Chugai Pharmaceutical Co., Ltd., and AbbVie Inc. The other authors have nothing to disclose.

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Suda, G., Ogawa, K., Yamamoto, Y. et al. Retreatment with sofosbuvir, ledipasvir, and add-on ribavirin for patients who failed daclatasvir and asunaprevir combination therapy. J Gastroenterol 52, 1122–1129 (2017). https://doi.org/10.1007/s00535-017-1328-z

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  • DOI: https://doi.org/10.1007/s00535-017-1328-z

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