title: Daclatasvir and asunaprevir treatment in patients with severe liver fibrosis by hepatitis C virus genotype 1b infection: Real-world data.
abstract: OBJECTIVE
  In this study, we investigated the real-world data of the first approved interferon-free regimen in Japan: daclatasvir and asunaprevir in chronic hepatitis C patients with severe fibrosis.
  
  
  METHODS
  Among 924 patients registered in our multicenter study, 535 patients were defined as having severe fibrosis with Fib-4 index ≧ 3.25 and were included in this study. We investigated antiviral effect and factors associated with sustained viral response 12 (SVR12), and the additional effects on serum α-fetoprotein and albumin levels by eradicating virus in patients who attained SVR were investigated. In statistical analysis, P < 0.05 was considered as significant levels.
  
  
  RESULTS
  Antiviral effect was lower in patients with severe fibrosis at 8 and 12 weeks after start of the treatment (96.3%, 97.1% with severe fibrosis vs 99.5%, 99.2% without severe fibrosis, P = 0.002 and P = 0.036, respectively), and more early relapse (SVR4; 90.4% with severe fibrosis vs 95.4% without fibrosis, P = 0.008) was seen in patients with severe fibrosis; however, there were no differences in SVR12 and SVR24. In the safety profiles, discontinuation rate due to liver injury (2.8% with severe fibrosis vs 3.3% without severe fibrosis) or other causes of discontinuation was not different between two groups. Serum α-fetoprotein significantly decreased, and serum albumin levels significantly increased as early as 4 weeks after the start of treatment.
  
  
  CONCLUSIONS
  Although the antiviral effect was slightly lower in patients with severe fibrosis compared with those without, treatment with daclatasvir and asunaprevir is basically an effective and well-tolerable treatment in these populations.
authors.affiliation: Department of Gastroenterology and Hepatology, School of Medicine, Nagoya University, Nagoya, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Ishigami
authors.affiliation: Department of Gastroenterology and Hepatology, School of Medicine, Nagoya University, Nagoya, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Hayashi
authors.affiliation: Department of Gastroenterology and Hepatology, School of Medicine, Nagoya University, Nagoya, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Honda
authors.affiliation: Department of Gastroenterology and Hepatology, School of Medicine, Nagoya University, Nagoya, Japan.
authors.forename: Teiji
authors.initials: T
authors.lastname: Kuzuya
authors.affiliation: Department of Gastroenterology and Hepatology, School of Medicine, Nagoya University, Nagoya, Japan.
authors.forename: Yoji
authors.identifier: http://orcid.org/0000-0002-1255-5201
authors.initials: Y
authors.lastname: Ishizu
authors.affiliation: Department of Gastroenterology and Hepatology, School of Medicine, Nagoya University, Nagoya, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ishikawa
authors.affiliation: Department of Gastroenterology and Hepatology, School of Medicine, Nagoya University, Nagoya, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Nakano
authors.affiliation: Department of Gastroenterology, Toyohashi Municipal Hospital, Toyohashi, Japan.
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Urano
authors.affiliation: Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kumada
authors.affiliation: Division of Liver and Biliary Diseases, Department of Internal Medicine, Fujita Health University, Toyoake, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yoshioka
authors.affiliation: Department of Gastroenterology and Hepatology, School of Medicine, Nagoya University, Nagoya, Japan.
authors.forename: Hidemi
authors.initials: H
authors.lastname: Goto
authors.affiliation: Department of Gastroenterology and Hepatology, School of Medicine, Nagoya University, Nagoya, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Hirooka
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage*; D002219:Carbamates; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage*; D007546:Isoquinolines / Q000008:administration & dosage*; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D011759:Pyrrolidines; D012720:Severity of Illness Index; D013449:Sulfonamides / Q000008:administration & dosage*; D016896:Treatment Outcome; D014633:Valine / Q000031:analogs & derivatives
chemical_list: D000998:Antiviral Agents; D002219:Carbamates; D007093:Imidazoles; D007546:Isoquinolines; D011759:Pyrrolidines; D013449:Sulfonamides; D014633:Valine; C549273:daclatasvir; C571889:asunaprevir
keywords: asunaprevir; daclatasvir; fibrosis; genotype 1b; hepatitis C