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

Norio Akuta, Joji Toyota, Yoshiyasu Karino, Fusao Ikeda, Akio Ido, Katsuaki Tanaka, Koichi Takaguchi, Atsushi Naganuma, Eiichi Tomita, Kazuaki Chayama, Shigetoshi Fujiyama, Yukiko Inada, Hitoshi Yoshiji, Hideaki Watanabe, Hiroki Ishikawa, Fiona McPhee, Stephanie Noviello, Hiromitsu Kumada

Research output: Contribution to journalArticle

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 > 10 7  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.

Original languageEnglish
Pages (from-to)1089-1097
Number of pages9
JournalJournal of Gastroenterology
Volume53
Issue number9
DOIs
Publication statusPublished - Sep 1 2018

Keywords

  • Alpha-fetoprotein
  • Asunaprevir
  • Beclabuvir
  • Daclatasvir
  • Fibrosis

ASJC Scopus subject areas

  • Gastroenterology

Fingerprint Dive into the research topics of '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'. Together they form a unique fingerprint.

  • Cite this

    Akuta, N., Toyota, J., Karino, Y., Ikeda, F., Ido, A., Tanaka, K., Takaguchi, K., Naganuma, A., Tomita, E., Chayama, K., Fujiyama, S., Inada, Y., Yoshiji, H., Watanabe, H., Ishikawa, H., McPhee, F., Noviello, S., & Kumada, H. (2018). 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. Journal of Gastroenterology, 53(9), 1089-1097. https://doi.org/10.1007/s00535-018-1445-3