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.
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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)
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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)
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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)
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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)
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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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DOI: https://doi.org/10.1007/s00535-020-01733-4