title: Use of simeprevir following pre-emptive pegylated interferon/ribavirin treatment for recurrent hepatitis C in living donor liver transplant recipients: a 12-week pilot study.
abstract: BACKGROUND
  The management of recurrent hepatitis C following liver transplantation remains a challenge.
  
  
  METHODS
  We prospectively investigated the efficacy and safety of simeprevir in combination with pegylated interferon and ribavirin in five patients undergoing living donor liver transplantation (LDLT) with recurrent hepatitis due to hepatitis C virus (HCV) genotype 1b.
  
  
  RESULTS
  As the immunosuppressive regimen, four received cyclosporine A (CsA) and one received tacrolimus (FK); no dose adjustment was made prior to the introduction of simeprevir, but the dose was accordingly modified afterwards. All five patients completed the intended 12-week treatment course without significant adverse events greater than grade 2, and no episodes of rejection were detected during the study period. The trough levels of CsA and FK were stably maintained. At week 12, HCV-RNA was not detectable in three of the five patients, whereas the HCV titer of the other two patients, including one with Q80L and V170I mutations at the HCV NS3 position, was at the lower level of quantification (1.2 log10 IU/ml).
  
  
  CONCLUSIONS
  Based on this pilot study, simeprevir-based triple therapy is safe and somewhat effective within the first 12 weeks in LDLT recipients with HCV recurrence. Further studies are warranted to obtain robust conclusions.
authors.affiliation: Organ Transplantation Service, The University of Tokyo Hospital, Tokyo, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Tanaka
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Sugawara
authors.forename: Nobuhisa
authors.initials: N
authors.lastname: Akamatsu
authors.forename: Junichi
authors.initials: J
authors.lastname: Kaneko
authors.forename: Sumihito
authors.initials: S
authors.lastname: Tamura
authors.forename: Taku
authors.initials: T
authors.lastname: Aoki
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Sakamoto
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Hasegawa
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kurosaki
authors.forename: Namiki
authors.initials: N
authors.lastname: Izumi
authors.forename: Norihiro
authors.initials: N
authors.lastname: Kokudo
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D004337:Drug Carriers; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D016031:Liver Transplantation / Q000009:adverse effects*; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011446:Prospective Studies; D012367:RNA, Viral / Q000032:analysis; D011994:Recombinant Proteins / Q000627:therapeutic use; D012008:Recurrence; D012254:Ribavirin / Q000627:therapeutic use*; D000069616:Simeprevir / Q000627:therapeutic use*; D013997:Time Factors; D066027:Transplant Recipients; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D004337:Drug Carriers; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D000069616:Simeprevir; C100416:peginterferon alfa-2a
keywords: Direct-acting antiviral drugs; Hepatitis C; Living donor liver transplantation; Simeprevir