title: Safety and efficacy of daclatasvir and asunaprevir in hepatitis C virus-infected patients with renal impairment.
abstract: OBJECTIVE
  Hepatitis C virus (HCV) infection is a risk factor for end-stage renal disease, renal graft failure, and hemodialysis patient mortality. However, the efficacy of direct-acting antiviral therapy for HCV-infected patients with renal impairment is unclear. Additionally, the promising NS5B inhibitor sofosbuvir has not been recommended for patients with severe renal impairment. In this prospective, multicenter study, we evaluated the efficacy and safety of daclatasvir and asunaprevir combination therapy, with a focus on patients with renal impairment.
  
  
  METHODS
  The study included 322 genotype 1 HCV-infected patients who received daclatasvir and asunaprevir combination therapy. The safety and sustained virological response was examined at 12 weeks after the end of treatment and safety was evaluated according to renal function.
  
  
  RESULTS
  Of 322 patients, 5% (16/322) and 2.5% (8/322) had chronic kidney disease stage G3b (estimated glomerular filtration rate [eGFR], 30-44 mL/min/1.73 m2) and stage G4/5 (eGFR, 15-29/<15 mL/min/1.73 m2), respectively. Baseline presence of the NS5A resistance-associated variant, previous simeprevir treatment, and HCV RNA titers, which were predictors of a sustained viral response, were similar between patients with eGFR <45 mL/min/1.73 m2and eGFR >45 mL/min/1.73 m2. Notably, the 12-week sustained viral response rate was comparable in patients with eGFR <45 mL/min/1.73 m2(100%, 24/24) and those with eGFR >45 mL/min/1.73 m2(88.9%, 265/298; P = 0.07). Treatment discontinuation rates and adverse events, including alanine aminotransferase elevation, anemia, and renal disorders, were similar between the two groups.
  
  
  CONCLUSIONS
  Daclatasvir and asunaprevir combination therapy for patients with renal dysfunction was highly effective and safe.
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Goki
authors.initials: G
authors.lastname: Suda
authors.affiliation: Department of Gastroenterology and Hepatology, Sapporo City General Hospital, Sapporo, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nagasaka
authors.affiliation: Department of Gastroenterology and Hepatology, Hakodate City General Hospital, Hakodate, Japan.
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Department of Gastroenterology and Hepatology, JCHO Hokkaido Hospital, Sapporo, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Furuya
authors.affiliation: Department of Gastroenterology and Hepatology, Hakodate Medical Association Hospital, Hakodate, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Kumagai
authors.affiliation: Department of Gastroenterology and Hepatology, Sapporo Hokuyu Hospital, Sapporo, Japan.
authors.forename: Mineo
authors.initials: M
authors.lastname: Kudo
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.|Department of Gastroenterology and Hepatology, Kushiro Rosai Hospital, Kushiro, Japan.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Terashita
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.|Department of Gastroenterology and Hepatology, Tomakomai City Hospital, Tomakomai, Japan.
authors.forename: Tomoe
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Department of Gastroenterology and Hepatology, Touei Hospital, Sapporo, Japan.
authors.forename: Izumi
authors.initials: I
authors.lastname: Tsunematsu
authors.affiliation: Department of Gastroenterology and Hepatology, JCHO Sapporo Hokushin Hospital.
authors.forename: Junichi
authors.initials: J
authors.lastname: Yoshida
authors.affiliation: Department of Gastroenterology and Hepatology, Hokkaido Gastroenterology Hospital, Sapporo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Meguro
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Kimura
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Ito
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Machiko
authors.initials: M
authors.lastname: Umemura
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Izumi
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Tsunematsu
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Fumiyuki
authors.initials: F
authors.lastname: Sato
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.|Department of Gastroenterology and Hepatology, Sapporo City General Hospital, Sapporo, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Tsukuda
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Nakai
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Sho
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Mitsuteru
authors.initials: M
authors.lastname: Natsuizaka
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Kenichi
authors.identifier: http://orcid.org/0000-0002-3891-5113
authors.initials: K
authors.lastname: Morikawa
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Ogawa
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Sakamoto
keywords: asunaprevir; daclatasvir; direct-acting antiviral; hepatitis C virus