title: Efficacy, safety, and pharmacokinetics of simeprevir, daclatasvir, and ribavirin in patients with recurrent hepatitis C virus genotype 1b infection after orthotopic liver transplantation: The Phase II SATURN study.
abstract: Recurrent hepatitis C virus (HCV) infection following liver transplantation is associated with accelerated progression to graft failure and reduced patient survival.
  
  
  
  The Phase II, open-label SATURN study (NCT01938625) investigated the combination of simeprevir (SMV), daclatasvir (DCV), and ribavirin (RBV) administered for 24 weeks in 35 patients with recurrent HCV genotype (GT) 1b infection after orthotopic liver transplantation (OLT).
  
  
  
  High rates of both on-treatment and sustained virologic response 12 weeks after end of treatment (SVR12) were achieved in patients who were either treatment-naïve or had failed post-OLT treatment with peginterferon and RBV. Overall, 91% of patients (32/35) achieved SVR12. The combination was generally well tolerated, with an adverse event profile consistent with that observed in previous clinical trials of SMV or DCV separately. Co-administration of SMV with cyclosporine resulted in significantly increased SMV plasma exposures, which was not the case with the co-administration of SMV with tacrolimus. Therefore, the concomitant use of SMV with cyclosporine is not recommended.
  
  
  
  The interferon-free combination of SMV, DCV, and RBV administered for 24 weeks was shown to be effective and well tolerated in the treatment of post-OLT HCV GT1b-infected patients.
authors.affiliation: Liver Unit, Hospital Clinic, IDIBAPS and CIBEREHD, University of Barcelona, Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Forns
authors.affiliation: Department of Digestive Diseases, Hepatology and Liver Transplantation Unit, La Fe University Hospital and CIBEREHD, Valencia, Spain.
authors.forename: Marina
authors.initials: M
authors.lastname: Berenguer
authors.affiliation: Department of General, Visceral and Transplantation Surgery and Department of Gastroenterology and Hepatology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Herzer
authors.affiliation: Department of Hepatobiliary and Transplant Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Sterneck
authors.affiliation: Division of Digestive Diseases, IRCCS Maggiore Hospital, Milan, Italy.
authors.forename: Maria Francesca
authors.initials: MF
authors.lastname: Donato
authors.affiliation: Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Andreone
authors.affiliation: Gastroenterology and Transplant Hepatology, Papa Giovanni XXIII Hospital, Bergamo, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Fagiuoli
authors.affiliation: Department of Immunology, Transplant Medicine and Internal Diseases, Transplantation Institute, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Cieciura
authors.affiliation: Department of Transplantation Medicine and Nephrology, Transplantation Institute, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Durlik
authors.affiliation: Liver Unit, Hospital Universitario Puerta de Hierro, CIBEREHD and IDIPHIM, Madrid, Spain.
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Calleja
authors.affiliation: Liver Unit, Hospital Clinic, IDIBAPS and CIBEREHD, University of Barcelona, Barcelona, Spain.
authors.forename: Zoe
authors.initials: Z
authors.lastname: Mariño
authors.affiliation: Janssen Research & Development, LLC, Titusville, NJ, USA.
authors.forename: Umesh
authors.initials: U
authors.lastname: Shukla
authors.affiliation: Janssen Pharmaceutica NV, Beerse, Belgium.
authors.forename: Thierry
authors.initials: T
authors.lastname: Verbinnen
authors.affiliation: Janssen Pharmaceutica NV, Beerse, Belgium.
authors.forename: Oliver
authors.initials: O
authors.lastname: Lenz
authors.affiliation: Janssen Research & Development, Beerse, Belgium.
authors.forename: Sivi
authors.initials: S
authors.lastname: Ouwerkerk-Mahadevan
authors.affiliation: Janssen Pharmaceutica NV, Beerse, Belgium.
authors.forename: Monika
authors.initials: M
authors.lastname: Peeters
authors.affiliation: Janssen Pharmaceutica NV, Beerse, Belgium.
authors.forename: Katrien
authors.initials: K
authors.lastname: Janssen
authors.affiliation: Janssen Research & Development, LLC, Titusville, NJ, USA.
authors.forename: Ronald
authors.initials: R
authors.lastname: Kalmeijer
authors.affiliation: Janssen Research & Development, LLC, Titusville, NJ, USA.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Jessner
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D002219:Carbamates; D016572:Cyclosporine / Q000627:therapeutic use; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000379:methods; D005260:Female; D005838:Genotype; D006084:Graft Rejection / Q000453:epidemiology / Q000517:prevention & control; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification*; D019698:Hepatitis C, Chronic / Q000628:therapy* / Q000821:virology; D006801:Humans; D007093:Imidazoles / Q000493:pharmacokinetics / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016898:Interferon-alpha / Q000627:therapeutic use; D016031:Liver Transplantation / Q000009:adverse effects* / Q000379:methods; D008297:Male; D008875:Middle Aged; D011759:Pyrrolidines; D012367:RNA, Viral / Q000302:isolation & purification; D012008:Recurrence; D012254:Ribavirin / Q000493:pharmacokinetics / Q000627:therapeutic use; D000069616:Simeprevir / Q000493:pharmacokinetics / Q000627:therapeutic use; D016559:Tacrolimus / Q000627:therapeutic use; D016896:Treatment Outcome; D014633:Valine / Q000031:analogs & derivatives; D019562:Viral Load / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D002219:Carbamates; D007093:Imidazoles; D007166:Immunosuppressive Agents; D016898:Interferon-alpha; D011759:Pyrrolidines; D012367:RNA, Viral; D012254:Ribavirin; D016572:Cyclosporine; D000069616:Simeprevir; D014633:Valine; C549273:daclatasvir; D016559:Tacrolimus
keywords: daclatasvir; hepatitis C virus; liver transplantation; ribavirin; simeprevir