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Efficacy and safety of ledipasvir/sofosbuvir with ribavirin in chronic hepatitis C patients who failed daclatasvir/asunaprevir therapy: pilot study

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Background

In Japan, daclatasvir (DCV) and asunaprevir (ASV) therapy was the first IFN-free treatment to be approved, and thousands of patients have since been successfully treated, with an SVR rate of around 90%. The converse, however, is that around 10% of patients fail to achieve viral eradication and must be retreated using a different approach. This study is to evaluate treatment efficacy of ledipasvir/sofosbuvir and ribavirin in patients who failed to respond to DCV and ASV therapy.

Methods

Thirty patients were treated with 12 weeks of ledipasvir/sofosbuvir and ribavirin. We evaluated the rate of sustained virological response 12 weeks after the end of treatment (SVR12) and examined the incidence of adverse events during ledipasvir/sofosbuvir and ribavirin treatment. NS5A and NS5B resistance-associated variants (RAVs) in treatment failure cases were examined.

Results

The overall SVR12 rate was 86.7% (26/30). Large decreases in mean log10 HCV RNA levels were observed in patients without cirrhosis, and the SVR12 rate for these patients was 100% (12/12). In cases of cirrhosis, SVR12 rate was 72.2% (13/18). The common factors in treatment failure cases were the presence of liver cirrhosis and both NS5A L31M/I and Y93H RAVs. The frequency of RAVs did not change before and after treatment among patients who relapsed.

Conclusion

Ledipasvir/sofosbuvir with ribavirin is an effective retreatment option for patients with chronic hepatitis C who failed to respond to prior daclatasvir and asunaprevir therapy.

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Abbreviations

RIKEN:

The Institute of Physical and Chemical Research

HCV:

Hepatitis C virus

SVR:

Sustained virological response

GT1:

Genotype 1

IFN:

Interferon

RBV:

Ribavirin

DAAs:

Direct-acting antiviral agents

DCV:

Daclatasvir

ASV:

Asunaprevir

LDV:

Ledipasvir

SOF:

Sofosbuvir

OBV:

Ombitasvir

PTV:

Paritaprevir

r:

Ritonavir

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

RAVs:

Resistance-associated variants

Hb:

Hemoglobin

EOT:

End of treatment

SAE:

Serious adverse event

AE:

Adverse event

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Acknowledgements

We thank Akemi Sada for clerical assistance, and Tsuyoshi Nagata for preparation of the manuscript. Part of this work was carried out at the Analysis Center of Life Science, Hiroshima University. This study was supported by the Research Program on Hepatitis from Japanese Agency for Medical and development (AMED) Japan (Grant Number16fk0210301h0003).

Author information

Authors and Affiliations

  1. Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan

    Yoshiiku Kawakami, Hidenori Ochi, Clair Nelson Hayes, Michio Imamura, Masataka Tsuge, Takashi Nakahara & Kazuaki Chayama

  2. Department of Center for Integrated Medical Research, Hiroshima University, Hiroshima, Japan

    Yoshiiku Kawakami

  3. Onomichi General Hospital, Hiroshima, Japan

    Yoshio Katamura

  4. Kure Medical Center, Hiroshima, Japan

    Hiroshi Kohno & Hirotaka Kohno

  5. Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, Hiroshima, Japan

    Keiji Tsuji, Shintaro Takaki, Nami Mori & Yohji Honda

  6. Tsuchiya General Hospital, Hiroshima, Japan

    Keiko Arataki

  7. Koyo New Town Hospital, Hiroshima, Japan

    Shoichi Takahashi

  8. Saiseikai Hiroshima Hospital, Hiroshima, Japan

    Shinsuke Kira

  9. Mazda Hospital, Hiroshima, Japan

    Toru Tamura

  10. Masuda Clinic, Hiroshima, Japan

    Kazunari Masuda

  11. Nakamura Clinic, Hiroshima, Japan

    Toshio Nakamura

  12. Kikkawa Clinic, Hiroshima, Japan

    Masaya Kikkawa

  13. Liver Research Project Center, Hiroshima University, Hiroshima, Japan

    Yoshiiku Kawakami, Hidenori Ochi, Clair Nelson Hayes, Michio Imamura, Masataka Tsuge, Takashi Nakahara & Kazuaki Chayama

  14. Laboratory for Digestive Diseases, RIKEN Center for Integrative Medical Sciences, The Institute of Physical and Chemical Research (RIKEN), Hiroshima, Japan

    Hidenori Ochi & Kazuaki Chayama

Authors
  1. Yoshiiku Kawakami
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Corresponding author

Correspondence to Kazuaki Chayama.

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Conflict of interest

K. Chayama has received research grants and consulting fees from Bristol-Myers Squibb, Dainippon Sumitomo Pharma, Mitsubishi Tanabe Pharma, Daiichi Sankyo, Toray Industries, Otsuka Pharmaceutical Company, and GlaxoSmithKline KK. All other authors have no conflicts to report.

Financial support

This study was supported in part by a Grant-in-Aid for Scientific Research from the Japanese Ministry of Labor and Health and Welfare.

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Kawakami, Y., Ochi, H., Hayes, C.N. et al. Efficacy and safety of ledipasvir/sofosbuvir with ribavirin in chronic hepatitis C patients who failed daclatasvir/asunaprevir therapy: pilot study. J Gastroenterol 53, 548–556 (2018). https://doi.org/10.1007/s00535-017-1380-8

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  • DOI: https://doi.org/10.1007/s00535-017-1380-8

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