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Potent viral suppression and improvements in alpha-fetoprotein and measures of fibrosis in Japanese patients receiving a daclatasvir/asunaprevir/beclabuvir fixed-dose combination for the treatment of HCV genotype-1 infection

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

Background

In the UNITY-3 study, 96% sustained virologic response (SVR12) rate was observed in Japanese patients with hepatitis C virus (HCV) genotype (GT)-1 infection treated for 12 weeks with fixed-dose daclatasvir, asunaprevir, and beclabuvir (DCV-TRIO). As HCV clearance may improve liver outcomes, we assessed hepatic fibrosis and alpha-fetoprotein (AFP), a hepatocellular carcinoma risk marker, pre- and post-treatment in UNITY-3.

Methods

Treatment-naive or interferon-experienced UNITY-3 patients with HCV GT-1 who received twice-daily DCV-TRIO were assessed for fibrosis [FibroTest; FibroScan; fibrosis-4 index (FIB-4), aspartate-aminotransferase-to-platelet-ratio index] and AFP at baseline and Weeks 4 (FIB-4 only), 12 or 24 post-treatment.

Results

Of 217 patients, 99% had GT-1b infection, 46% were aged > 65 years, 21% had compensated cirrhosis, and 26% baseline HCV-RNA > 107 IU/mL. All GT-1b patients treated ≥ 4 weeks achieved SVR12 with (n = 54) or without (n = 144) baseline NS5A polymorphisms associated with DCV resistance (positions 28/30/31/93). Statistically significant post-treatment reductions from baseline were observed for all fibrosis measures and AFP, with numerically greater reductions in cirrhotic patients. FibroTest category improved in 44%, remained stable in 50%, and worsened in 6% of patients; 98% with baseline AFP < 6 μg/L remained < 6 μg/L and 51% with baseline AFP ≥ 6 μg/L were < 6 μg/L post-treatment.

Conclusions

DCV-TRIO administered for 12 weeks to Japanese patients with primarily GT-1b infection achieved a high SVR12 rate and resulted in improved measures of hepatic fibrosis and serum AFP that may reduce the risk of future liver disease progression and hepatocellular carcinoma, particularly in those with compensated cirrhosis.

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Acknowledgements

The authors thank Yue Zhao for her important statistical contributions to this study. UNITY-3 was a phase 3 study sponsored by Bristol-Myers Squibb. Editorial assistance with this manuscript was provided by Andrew Stead, PhD, of Articulate-Science LLC, Manchester, UK, and funded by Bristol-Myers Squibb.

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Authors and Affiliations

  1. Toranomon Hospital, Tokyo, Japan

    Norio Akuta & Hiromitsu Kumada

  2. Sapporo-Kosei General Hospital, Sapporo, Japan

    Joji Toyota & Yoshiyasu Karino

  3. Okayama University, Okayama, Japan

    Fusao Ikeda

  4. Kagoshima University, Kagoshima, Japan

    Akio Ido

  5. Yokohama City University Medical Center, Yokohama, Japan

    Katsuaki Tanaka

  6. Kagawa Prefectural Central Hospital, Takamatsu, Japan

    Koichi Takaguchi

  7. Takasaki General Medical Center, Takasaki, Japan

    Atsushi Naganuma

  8. Gifu Municipal Hospital, Gifu, Japan

    Eiichi Tomita

  9. Hiroshima University, Hiroshima, Japan

    Kazuaki Chayama

  10. Kumamoto Shinto General Hospital, Kumamoto, Japan

    Shigetoshi Fujiyama

  11. Miyazaki Medical Center Hospital, Miyazaki, Japan

    Yukiko Inada

  12. Nara Medical University, Kashihara, Japan

    Hitoshi Yoshiji

  13. Bristol-Myers Squibb K.K., Tokyo, Japan

    Hideaki Watanabe & Hiroki Ishikawa

  14. Bristol-Myers Squibb, Wallingford, CT, USA

    Fiona McPhee

  15. Bristol-Myers Squibb, Princeton, NJ, USA

    Stephanie Noviello

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  1. Norio Akuta
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Corresponding author

Correspondence to Norio Akuta.

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Conflict of interest

K Takaguchi has received speaker fees from Bristol-Myers Squibb K.K. AbbVie, and AstraZeneca K.K. A. Ido has received speaker fees from Bristol-Myers Squibb K.K. Gilead, and AbbVie; and commercial research funding from Eisai, EA Pharma, and Bristol-Myers Squibb K.K. Y. Karino has received speaker fees from Bristol-Myers Squibb K.K. MSD, AbbVie, Gilead, and Dainippon Sumitomo Pharma. K. Chayama has received speaker fees from MSD, Bristol-Myers Squibb K.K., and AbbVie. H. Watanabe and H. Ishikawa are employees of Bristol-Myers Squibb K.K. F. McPhee is an employee and holds stock in Bristol-Myers Squibb. S Noviello is an employee of Bristol-Myers Squibb; and holds stock in Bristol-Myers Squibb, Merck, and Johnson & Johnson. H. Kumada has received speaker fees from AbbVie, Gilead, Bristol-Myers Squibb K.K. MSD, and Dainippon Sumitomo Pharma. F. Ikeda, K. Tanaka, A. Naganuma, E. Tomita, S. Fujiyama, Y. Inada, N. Akuta, J. Toyota, and H. Yoshiji have no conflicts of interest to disclose.

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Akuta, N., Toyota, J., Karino, Y. et al. Potent viral suppression and improvements in alpha-fetoprotein and measures of fibrosis in Japanese patients receiving a daclatasvir/asunaprevir/beclabuvir fixed-dose combination for the treatment of HCV genotype-1 infection. J Gastroenterol 53, 1089–1097 (2018). https://doi.org/10.1007/s00535-018-1445-3

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