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Sofosbuvir plus velpatasvir treatment for hepatitis C virus in patients with decompensated cirrhosis: a Japanese real-world multicenter study

Journal of Gastroenterology volume 56, pages 67–77 (2021)Cite this article

Abstract

Background

Real-world data on the efficacy and safety of sofosbuvir plus velpatasvir (SOF/VEL) treatment for patients with hepatitis C virus (HCV)-related decompensated cirrhosis are limited in Japan.

Methods

A total of 190 patients with compensated (108) or decompensated (82) cirrhosis who initiated direct-acting antiviral (DAA) treatment between February 2019 and August 2019 were enrolled. Sustained virologic response (SVR) was defined as undetectable serum HCV-RNA at 12 weeks after the end of treatment (EOT).

Results

The SVR12 rates were 92.6% in patients with compensated cirrhosis and 90.2% in patients with decompensated cirrhosis (p = 0.564), and the treatment completion rates were 98.1% and 96.3%, respectively (p = 0.372). In patients with decompensated cirrhosis, 3 patients discontinued treatment and 2 patients died because of liver-related events. In patients with decompensated cirrhosis with SVR12, 50% of patients with Child–Pugh class B at baseline showed improvement to class A at SVR12, and 27% and 9% of patients with Child–Pugh class C at baseline showed improvement to class B and class A at SVR12, respectively. Patients who achieved SVR12 showed elevated serum albumin levels at the EOT, which were further elevated at SVR12, but no elevated serum albumin levels after the EOT were observed in patients with baseline serum albumin levels less than 2.8 g/dl.

Conclusions

Real-world efficacy of SOF/VEL treatment for patients with decompensated cirrhosis was similar to Japanese phase 3 study, although treatment discontinuation and death related to liver disease occurred. In patients with poor hepatic reserve, whether it improves continuously after viral clearance requires further evaluation.

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Abbreviations

HCV:

Hepatitis C virus

DAA:

Direct-acting antiviral

SOF:

Sofosbuvir

NS:

Nonstructural

VEL:

Velpatasvir

RBV:

Ribavirin

SVR:

Sustained virologic response

LDV:

Ledipasvir

EBR:

Elbasvir

GZR:

Grazoprevir

GLE:

Glecaprevir

PIB:

Pibrentasvir

EOT:

End of treatment

RM ANOVA:

Repeated measures analysis of variance

MELD:

Model for end-stage liver disease

IQR:

Interquartile range

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Acknowledgements

The authors thank Yoshito Uchida (Department of Gastroenterology and Hepatology, Saitama Medical University), Sawako Uchida (Department of Hepatology, Graduate School of Medicine, Osaka City University), Shinnya Maekawa (First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi), Kotaro Kumagai (Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medicine and Dental Sciences), Hiroaki Takatani (Department of Gastroenterology, Nara Medical University), Yohei Koizumi (Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine), Hidekatsu Kuroda (Division of Hepatology, Deportment of Internal Medicine, Iwate Medical University), Shun Kaneko (Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital), Satoru Hashimoto, Kazumasa Tajima (Clinical Research Center, National Hospital Organization Nagasaki Medical Center), Tatsuya Minami (Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo), Kazuo Okumoto (Department of Gastroenterology, Faculty of Medicine, Yamagata University), Yuya Seko (Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine), Yosuke Osawa (The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine), Tatsushi Naito (Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui), Masato Nakamura (Department of Gastroenterology, Graduate School of Medicine, Chiba University), Miyako Murakawa (Department of Gastroenterology and Hepatology, Department of Liver Disease Control, Tokyo Medical and Dental University,), Atsunori Tsuchiya (Division of Gastroenterology and Hepatology, Graduate School of Medicine and Dental Sciences, Niigata University), Masanori Fukushima (Department of Gastroenterology and Hepatology, Nagasaki University of Graduate School of Biomedical Sciences), Tatsunori Hanai (Department of Gastroenterology/Internal Medicine Gifu University Graduate School of Medicine) and Takuro Hisanaga (Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine) for data collection and Rina Okada (Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine) and Hiroyuki Araki (Osaka University Graduate School of Medicine Department of Biostatistics and Data Science) for data management.

Funding

This work was partially supported by a Grant-in-Aid for Research on Hepatitis from the Ministry of Health Labor and Welfare of Japan, and the Japan Agency for Medical Research and Development (JP20fk0210058), and Gilead Sciences, Inc.

Author information

Affiliations

  1. Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Yuki Tahata, Hayato Hikita, Ryotaro Sakamori, Ryoko Yamada, Takahiro Kodama, Tomohide Tatsumi & Tetsuo Takehara

  2. Department of Gastroenterology and Hepatology, Saitama Medical University, Saitama, Japan

    Satoshi Mochida

  3. Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan

    Norifumi Kawada

  4. First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan

    Nobuyuki Enomoto

  5. Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medicine and Dental Sciences, Kagoshima, Japan

    Akio Ido

  6. Department of Gastroenterology, Nara Medical University, Nara, Japan

    Hitoshi Yoshiji

  7. Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan

    Daiki Miki

  8. Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan

    Yoichi Hiasa

  9. Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Iwate, Japan

    Yasuhiro Takikawa

  10. Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan

    Masayuki Kurosaki

  11. Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Nagasaki, Japan

    Hiroshi Yatsuhashi

  12. Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

    Ryosuke Tateishi

  13. Department of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata, Japan

    Yoshiyuki Ueno

  14. Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Yoshito Itoh

  15. Department of General Medicine, Kanazawa University Hospital, Kanazawa, Japan

    Taro Yamashita

  16. The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Chiba, Japan

    Tatsuya Kanto

  17. Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan

    Goki Suda

  18. Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan

    Yasunari Nakamoto

  19. Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan

    Naoya Kato

  20. Department of Gastroenterology and Hepatology, Department of Liver Disease Control, Tokyo Medical and Dental University, Tokyo, Japan

    Yasuhiro Asahina

  21. Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

    Kentaro Matsuura

  22. Division of Gastroenterology and Hepatology, Graduate School of Medicine and Dental Sciences, Niigata University, Niigata, Japan

    Shuji Terai

  23. Department of Gastroenterology and Hepatology, Nagasaki University of Graduate School of Biomedical Sciences, Nagasaki, Japan

    Kazuhiko Nakao

  24. Department of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan

    Masahito Shimizu

  25. Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan

    Taro Takami

  26. Department of Hepatology, Toranomon Hospital, Tokyo, Japan

    Norio Akuta

  27. Department of Medical Innovation, Osaka University Hospital, Suita, Osaka, Japan

    Tomomi Yamada

Authors
  1. Yuki Tahata
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  2. Hayato Hikita
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Corresponding author

Correspondence to Tetsuo Takehara.

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Conflict of interest

Satoshi Mochida received grants from Kowa Co, Ltd. CMIC Co., Ltd, AbbVie GK, Janssen Pharmaceutical K. K., EA Pharma Co, Ltd MIC Medical Corp. Sumitomo Dainippon Pharma Co., Ltd, Mochida Pharmaceutical Co., Ltd. Daiichi Sankyo Co., Ltd, Toray Indutries Inc, Chugai Pharmaceutical Co., Ltd, Asuka Pharmaceutical Co., Ltd, Eisai Co., Ltd. and Gilead Sciences, Inc. and is on the speakers’ bureau for Gilead Sciences, Inc., Bristol-Myers Squibb Company, MSD, Otuka Pharmaceutical Co., Ltd. Sumitomo Dainippon Pharma Co., Ltd. Asuka Pharmaceutical Co., Ltd and AbbVie GK and received patent royalties from SRL Inc. Norifumi Kawada received grants from Gilead Sciences, Inc. and AbbVie GK. and is on the speakers’ bureau for Gilead Sciences, Inc., MSD and AbbVie GK.. Nobuyuki Enomoto received grants from Gilead Sciences, Inc. and is on the speakers’ bureau for Gilead Sciences, Inc.. Akio Ido received grants from AbbVie GK. and is on the speakers’ bureau for Gilead Sciences, Inc., Bristol-Myers Squibb Company and AbbVie GK.. Masayuki Kurosaki is on the speakers’ bureau for Gilead Sciences, Inc. Hiroshi Yatsuhashi received grants from AbbVie GK. Yoshiyuki Ueno received grants from EA Pharma Co and AbbVie GK. and is on the speakers’ bureau for AbbVie GK., EA Pharma Co, and Otsuka Pharmaceutical Co. Yoshito Itoh received grants from AbbVie GK, Bristol-Myers Squibb Company, Gilead Sciences, Inc and MSD and is on the speakers’ bureau for Gilead Sciences, Inc., Bristol-Myers Squibb Company, MSD and AbbVie GK.. Tatsuya Kanto is on the speakers’ bureau for Gilead Sciences, Inc.and MSD. Goki Suda received grants from Gilead Sciences, Inc.. Naoya Kato received grants from Gilead Sciences, Inc., Bristol-Myers Squibb Company and AbbVie GK. and is on the speakers’ bureau for Gilead Sciences, Inc., MSD, Bristol-Myers Squibb Company and AbbVie GK.. Yasuhiro Asahina belongs to a donation-funded department funded by Toray Industries Inc, Gilead Sciences Inc, AbbVie GK, and Fujirebio Inc, Chugai Pharmaceutical Co. Ltd. and MSD. Shuji Terai received grants from Intersterm Routo, Asuka, Tsumura, Chiome Biosciense, Systemx, Touso, Abbvie, Takeda, Eisai, Kyowa, BioMimetics Sympathies and Daiichisannkyo and is on the speakers’ bureau for Gilead Sciences, Inc., Asuka, MSD, Otsuka, Daiichisannkyo and Takeda. Norio Akuta is on the speakers’ bureau for Gilead Sciences, Inc., Bristol-Myers Squibb Company, MSD, Dainippon Sumitomo Pharma, Mitsubishi Tanabe Pharma Co. Ltd and AbbVie GK. Takahiro Kodama received grants from Gilead Sciences, Inc. and AbbVie GK.. Tetsuo Takehara received grants from Gilead Sciences, Inc., MSD, and AbbVie GK. and is on the speakers’ bureau for Gilead Sciences, Inc., MSD, and AbbVie GK.. All other authors declare that they have no conflicts of interest to disclose.

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535_2020_1733_MOESM1_ESM.tif

Supplementary file1 Figure 1. Treatment completion rates according to liver cirrhosis. Gray box, patients with compensated cirrhosis. White box, patients with decompensated cirrhosis. (TIF 852 kb)

535_2020_1733_MOESM2_ESM.tif

Supplementary file2 Figure 2. Flow chart of patients who were included in the examination of the changes in liver function during follow-up. (TIF 1142 kb)

535_2020_1733_MOESM3_ESM.tif

Supplementary file3 Figure 3. Changes in liver function score at SVR12 from baseline among patients with SVR12 according to liver cirrhosis. A Child-Pugh score. bMELD score. Gray box, patients with compensated cirrhosis. White box, patients with decompensated cirrhosis. (TIF 864 kb)

535_2020_1733_MOESM4_ESM.tif

Supplementary file4 Figure 4. Changes in Child-Pugh score of each liver function according to liver cirrhosis and baseline Child-Pugh score among patients with SVR12. A Albumin level. B Total bilirubin level. C Prothrombin activation. D Ascites. E Encephalopathy (TIF 1356 kb)

Supplementary file5 (DOCX 15 kb)

Supplementary file6 (DOCX 20 kb)

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Tahata, Y., Hikita, H., Mochida, S. et al. Sofosbuvir plus velpatasvir treatment for hepatitis C virus in patients with decompensated cirrhosis: a Japanese real-world multicenter study. J Gastroenterol 56, 67–77 (2021). https://doi.org/10.1007/s00535-020-01733-4

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Keywords

  • Liver cirrhosis
  • Direct-acting antiviral
  • Liver function
  • Albumin
  • Sustained virologic response