title: Safety and efficacy of dual direct-acting antiviral therapy (daclatasvir and asunaprevir) for chronic hepatitis C virus genotype 1 infection in patients on hemodialysis.
abstract: BACKGROUND
  Hepatitis C virus (HCV) infection is a major comorbidity in patients receiving hemodialysis. Interferon-based antiviral therapy to eradicate HCV is less effective in patients receiving hemodialysis than patients without renal dysfunction. Recently reported combination therapy with two oral direct-acting antiviral drugs, daclatasvir and asunaprevir, both of which are metabolized in the liver and excreted into the bile ducts, reportedly showed a high rate of HCV eradication. We evaluated the safety and efficacy of this therapy in patients receiving hemodialysis.
  
  
  METHODS
  The safety and viral responses were compared among patients infected with HCV genotype 1, between 28 patients receiving hemodialysis, and propensity score-matched 56 patients without renal dysfunction.
  
  
  RESULTS
  The reduction in serum HCV RNA levels 1 day after the start of therapy was significantly larger (p = 0.0329) and the disappearance of serum HCV RNA occurred significantly earlier (p = 0.0017) in patients receiving hemodialysis than those without renal dysfunction. The rates of sustained virologic response, i.e., the eradication of HCV, were comparable between two groups; the rate of SVR12 was 100 % in patients receiving hemodialysis and 94.6 % in patients without renal dysfunction. No adverse constitutional events were observed in either of the groups. The elevation of serum alanine aminotransferase levels, a known adverse effect of these drugs, was observed in comparable rate of patients between the two groups.
  
  
  CONCLUSIONS
  The therapy with daclatasvir and asunaprevir has high antiviral efficacy in patients receiving hemodialysis with a comparable safety profile to patients without renal dysfunction.
authors.affiliation: Department of Gastroenterology, Ogaki Municipal Hospital, 4-86 Minaminokawa, Ogaki, Gifu, 503-8502, Japan. hmtoyoda@spice.ocn.ne.jp.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Toyoda
authors.affiliation: Department of Gastroenterology, Ogaki Municipal Hospital, 4-86 Minaminokawa, Ogaki, Gifu, 503-8502, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kumada
authors.affiliation: Department of Gastroenterology, Ogaki Municipal Hospital, 4-86 Minaminokawa, Ogaki, Gifu, 503-8502, Japan.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Tada
authors.affiliation: Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Takaguchi
authors.affiliation: Department of Hepatology, Saiseikai Niigata Daini Hospital, Niigata, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Ishikawa
authors.affiliation: Center for Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan.
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Tsuji
authors.affiliation: Department of Gastroenterology, Sanno Hospital, International University of Health and Welfare, Tokyo, Japan.
authors.forename: Mikio
authors.initials: M
authors.lastname: Zeniya
authors.affiliation: Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Science, Nagoya, Japan.|Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Science, Nagoya, Japan.
authors.forename: Etsuko
authors.initials: E
authors.lastname: Iio
authors.affiliation: Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Science, Nagoya, Japan.
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Tanaka
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D002219:Carbamates; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D007546:Isoquinolines / Q000627:therapeutic use*; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011759:Pyrrolidines; D006435:Renal Dialysis; D013449:Sulfonamides / Q000627:therapeutic use*; 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: Chronic hepatitis C; Direct-acting antiviral drugs; Hemodialysis; Safety; Viral response