title: Daclatasvir plus asunaprevir for chronic HCV genotype 1b infection.
abstract: All-oral combinations of direct-acting antivirals may improve efficacy and safety outcomes for patients with hepatitis C virus (HCV) infection, particularly those who are poor candidates for current interferon/ribavirin-based regimens. In this open-label, phase 3 study, 135 interferon-ineligible/intolerant and 87 nonresponder patients with chronic HCV genotype 1b infection were enrolled at 24 centers in Japan. Patients received daclatasvir 60 mg once daily plus asunaprevir 100 mg twice daily for 24 weeks. The primary endpoint was sustained virologic response 24 weeks after treatment (SVR24 ). This study is registered with ClinicalTrials.gov (NCT01497834). SVR24 was achieved by 87.4% of interferon-ineligible/intolerant patients and 80.5% of nonresponder (null and partial) patients; rates were similar in cirrhosis (90.9%) and noncirrhosis (84.0%) patients, and in patients with IL28B CC (84.5%) or non-CC (84.8%) genotypes. Fourteen patients in each group (12.6%) discontinued dual therapy, mainly due to adverse events or lack of efficacy. Nine nonresponder patients received additional treatment with peginterferon/ribavirin per protocol-defined criteria. The rate of serious adverse events was low (5.9%) and varied among patients. The most common adverse events were nasopharyngitis, increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST), headache, diarrhea, and pyrexia.
  
  
  CONCLUSIONS
  Interferon-free, ribavirin-free all-oral therapy with daclatasvir and asunaprevir for 24 weeks is well tolerated and can achieve a high rate of SVR in patients with HCV genotype 1b who were ineligible, intolerant, or had not responded to prior interferon-based therapy. (Hepatology 2014;59:2083-2091).
authors.affiliation: Toranomon Hospital, Tokyo, Japan.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Kumada
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Kenji
authors.initials: K
authors.lastname: Ikeda
authors.forename: Joji
authors.initials: J
authors.lastname: Toyota
authors.forename: Yoshiyasu
authors.initials: Y
authors.lastname: Karino
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
authors.forename: Yoshiiku
authors.initials: Y
authors.lastname: Kawakami
authors.forename: Akio
authors.initials: A
authors.lastname: Ido
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Koichi
authors.initials: K
authors.lastname: Takaguchi
authors.forename: Namiki
authors.initials: N
authors.lastname: Izumi
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Koike
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Takehara
authors.forename: Norifumi
authors.initials: N
authors.lastname: Kawada
authors.forename: Michio
authors.initials: M
authors.lastname: Sata
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Miyagoshi
authors.forename: Timothy
authors.initials: T
authors.lastname: Eley
authors.forename: Fiona
authors.initials: F
authors.lastname: McPhee
authors.forename: Andrew
authors.initials: A
authors.lastname: Damokosh
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ishikawa
authors.forename: Eric
authors.initials: E
authors.lastname: Hughes
mesh_terms: D000328:Adult; D000368:Aged; D002219:Carbamates; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D007546:Isoquinolines / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011759:Pyrrolidines; D012367:RNA, Viral / Q000097:blood; D013449:Sulfonamides / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D017211:Treatment Failure; D014633:Valine / Q000031:analogs & derivatives; D055815:Young Adult
chemical_list: D002219:Carbamates; D007093:Imidazoles; D007546:Isoquinolines; D011759:Pyrrolidines; D012367:RNA, Viral; D013449:Sulfonamides; D014633:Valine; C549273:daclatasvir; C571889:asunaprevir