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Real-world efficacy and safety of ledipasvir and sofosbuvir in patients with hepatitis C virus genotype 1 infection: a nationwide multicenter study by the Japanese Red Cross Liver Study Group

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

Abstract

Background

We aimed to describe the real-world efficacy and safety of combination therapy with ledipasvir and sofosbuvir (LDV/SOF) for chronic hepatitis C virus (HCV) genotype 1 (GT1) infection.

Methods

This retrospective analysis of a prospective, nationwide, multicenter registry included GT1-infected patients treated with LDV/SOF for 12 weeks. We assessed the rate of sustained virological response at 12 weeks post-treatment (SVR12), incidence of adverse events, and serum markers of hepatocellular carcinoma (HCC).

Results

Among the 1461 patients included (mean age, 69 years; 29.5% aged > 75 years; cirrhosis, 23.8%; history of treatment for HCC, 10.9%), the overall SVR12 rate was 98.4% (1438/1461). Factors associated with treatment failure were cirrhosis (odds ratio, 4.19; p = 0.014) and resistance-associated substitutions (RASs) in NS5A at baseline (odds ratio, 7.78; p = 0.0004). The SVR12 rate in patients with cirrhosis and NS5A RASs was 93.0% compared to 100% in patients without cirrhosis or NS5A RASs. In patients with SVR, the levels of alpha-fetoprotein (AFP), AFP-L3, and Mac-2 binding protein glycosylation isomer (M2BPGi) decreased from baseline to end of treatment (from 13.4 ± 37.6 to 6.0 ± 10.6 ng/mL, p < 0.0001; from 2.2 ± 4.9 to 1.5 ± 6.3%, p < 0.005; and from 3.6 ± 3.7 to 2.0 ± 3.5 cut-off index, p < 0.0001; respectively). Adverse events were rare and not associated with age. No decrease in estimated glomerular filtration rate was observed in patients with baseline chronic kidney disease stage 3.

Conclusions

LDV/SOF therapy is highly effective and safe in elderly Japanese patients with HCV GT1, even in the presence of cirrhosis or NS5A RASs. Patients with SVR may have a lower risk of HCC.

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Acknowledgements

This study was supported by a Grant-in aid from the Japan Agency for Medical Research and Development (Grant number: 15fk0210007h0002).

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Authors and Affiliations

  1. Department of Gastroenterology, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, Hiroshima, Hiroshima, Japan

    Keiji Tsuji, Nami Mori & Shintaro Takaki

  2. Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, 1-26-1 Kyonan-cho, Musashino-shi, Tokyo, 180-8610, Japan

    Masayuki Kurosaki, Jun Itakura & Namiki Izumi

  3. Department of Gastroenterology, Japanese Red Cross Asahikawa Hospital, Asahikawa, Hokkaido, Japan

    Chitomi Hasebe

  4. Department of Gastroenterology, Japanese Red Cross Ishinomaki Hospital, Ishinomaki, Miyagi, Japan

    Takehiro Akahane

  5. Center for Liver-Biliary-Pancreatic Disease, Matsuyama Red Cross Hospital, Matsuyama, Ehime, Japan

    Kouji Joko

  6. Department of Gastroenterology, Japanese Red Cross Akita Hospital, Akita, Akita, Japan

    Hitoshi Yagisawa

  7. Department of Internal Medicine, Japanese Red Cross Haramachi Hospital, Haramachi, Gunma, Japan

    Jirou Takezawa

  8. Department of Gastroenterology, Japanese Red Cross Medical Center, Shibuya-ku, Tokyo, Japan

    Ryou Nakata

  9. Department of Gastroenterology, Japanese Red Cross Nagoya Daini Hospital, Nagoya, Aichi, Japan

    Atsunori Kusakabe

  10. Department of Hepatology, Japanese Red Cross Ise Hospital, Ise, Mie, Japan

    Yuji Kojima

  11. Department of Gastroenterology, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan

    Hiroyuki Kimura

  12. Department of Gastroenterology, Takatsuki Red Cross Hospital, Takatsuki, Osaka, Japan

    Takashi Tamada

  13. Department of Gastroenterology, Japanese Red Cross Okayama Hospital, Okayama, Okayama, Japan

    Haruhiko Kobashi

  14. Department of Gastroenterology, Japanese Red Cross Tottori Hospital, Tottori, Tottori, Japan

    Akeri Mitsuda

  15. Department of Gastroenterology, Japanese Red Cross Otsu Hospital, Otsu, Shiga, Japan

    Masahiko Kondou

  16. Department of Gastroenterology, Takamatsu Red Cross Hospital, Takamatsu, Kagawa, Japan

    Chikara Ogawa

  17. Department of Gastroenterology, Matsue Red Cross Hospital, Matsue, Shimane, Japan

    Yasushi Uchida

  18. Department of Hepatology, Japanese Red Cross Fukuoka Hospital, Fukuoka, Fukuoka, Japan

    Tetsuro Sohda

  19. Department of Gastroenterology, Oita Red Cross Hospital, Oita, Oita, Japan

    Ryouichi Narita

Authors
  1. Keiji Tsuji
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  2. Masayuki Kurosaki
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  3. Jun Itakura
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  4. Nami Mori
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  5. Shintaro Takaki
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  6. Chitomi Hasebe
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  7. Takehiro Akahane
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  8. Kouji Joko
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  9. Hitoshi Yagisawa
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  10. Jirou Takezawa
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  11. Ryou Nakata
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  12. Atsunori Kusakabe
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  13. Yuji Kojima
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  14. Hiroyuki Kimura
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  15. Takashi Tamada
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  16. Haruhiko Kobashi
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  17. Akeri Mitsuda
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  18. Masahiko Kondou
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  19. Chikara Ogawa
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  20. Yasushi Uchida
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  21. Tetsuro Sohda
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  22. Ryouichi Narita
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  23. Namiki Izumi
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Corresponding author

Correspondence to Namiki Izumi.

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Tsuji, K., Kurosaki, M., Itakura, J. et al. Real-world efficacy and safety of ledipasvir and sofosbuvir in patients with hepatitis C virus genotype 1 infection: a nationwide multicenter study by the Japanese Red Cross Liver Study Group. J Gastroenterol 53, 1142–1150 (2018). https://doi.org/10.1007/s00535-018-1455-1

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  • DOI: https://doi.org/10.1007/s00535-018-1455-1

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