title: Efficacy and safety of sofosbuvir/ledipasvir for the treatment of patients with hepatitis C virus re-infection after liver transplantation.
abstract: BACKGROUND
  Hepatitis C virus (HCV) infection is associated with a particularly poor outcome after liver transplantation. In December 2014, sofosbuvir/ledipasvir (SOF/LDV) fixed-dose combination (FDC) was approved for HCV genotype 1 and 4 in Europe. In orthotopic liver transplantation (OLT) recipients, the interferon-free treatment of HCV re-infection with novel direct-acting antivirals has been demonstrated to be safe and effective in clinical trials, but real-world data are missing. The aim of this study was to investigate the safety and efficacy of SOF/LDV FDC in OLT recipients in the real-life setting.
  
  
  METHODS
  All consecutive OLT patients started on SOF/LDV FDC for 12 or 24 weeks at the University Medical Center Hamburg-Eppendorf and Medical School Hannover between October 2014 and August 2015 were retrospectively analyzed (n = 30). The primary efficacy endpoint was sustained virological response (SVR), i.e., absence of viremia 12 weeks after end of treatment (SVR 12). Liver function tests, creatinine, blood count, and HCV RNA (by polymerase chain reaction assay) were determined at each visit.
  
  
  RESULTS
  SVR was achieved in 29/30 patients (96.67%) treated with SOF/LDV ± ribavirin (RBV) for 12 (n = 4) or 24 weeks (n = 25). Twenty-five patients (86.2%) received RBV. However, in 15 of the 25 patients, RBV administration had to be discontinued because of severe anemia (57.7%). One RBV-treated patient died of a myocardial infarction during antiviral therapy; this event was most likely not directly related to SOF/LDV. Aside from RBV-associated anemia, no severe side effects of the antiviral regimen were observed.
  
  
  CONCLUSIONS
  Antiviral treatment with SOF/LDV is highly effective, safe, and well tolerated in OLT recipients. The addition of RBV often results in severe anemia, requiring dose reduction or discontinuation.
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Medical School Hannover, Hannover, Germany.|Integrated Research and Treatment Center - Transplantation (IFB-Tx), Medical School Hannover, Hannover, Germany.|German Center for Infection Research (DZIF), Hannover-Braunschweig site, Hannover, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Ciesek
authors.affiliation: Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Proske
authors.affiliation: Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.|German Center for Infection Research (DZIF), Hamburg-Lübeck-Borstel site, Hamburg, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Otto
authors.affiliation: Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.|German Center for Infection Research (DZIF), Hamburg-Lübeck-Borstel site, Hamburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Pischke
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Medical School Hannover, Hannover, Germany.|German Center for Infection Research (DZIF), Hannover-Braunschweig site, Hannover, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Costa
authors.affiliation: Institute for Medical Microbiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Lüthgehetmann
authors.affiliation: Institute for Medical Microbiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Polywka
authors.affiliation: Integrated Research and Treatment Center - Transplantation (IFB-Tx), Medical School Hannover, Hannover, Germany.|German Center for Infection Research (DZIF), Hannover-Braunschweig site, Hannover, Germany.|General-, Visceral- and Transplant Surgery, Medical School Hannover, Hannover, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Klempnauer
authors.affiliation: Department of Hepatobiliary Surgery and Visceral Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Nashan
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Medical School Hannover, Hannover, Germany.|Integrated Research and Treatment Center - Transplantation (IFB-Tx), Medical School Hannover, Hannover, Germany.|German Center for Infection Research (DZIF), Hannover-Braunschweig site, Hannover, Germany.
authors.forename: M P
authors.initials: MP
authors.lastname: Manns
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Medical School Hannover, Hannover, Germany.|German Center for Infection Research (DZIF), Hannover-Braunschweig site, Hannover, Germany.
authors.forename: T
authors.initials: T
authors.lastname: von Hahn
authors.affiliation: Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: A W
authors.initials: AW
authors.lastname: Lohse
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Medical School Hannover, Hannover, Germany.|German Center for Infection Research (DZIF), Hannover-Braunschweig site, Hannover, Germany.|Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Wedemeyer
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Medical School Hannover, Hannover, Germany.|Integrated Research and Treatment Center - Transplantation (IFB-Tx), Medical School Hannover, Hannover, Germany.|German Center for Infection Research (DZIF), Hannover-Braunschweig site, Hannover, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Mix
authors.affiliation: Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.|German Center for Infection Research (DZIF), Hamburg-Lübeck-Borstel site, Hamburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Sterneck
mesh_terms: D000368:Aged; D000410:Alanine Transaminase / Q000378:metabolism; D000998:Antiviral Agents / Q000494:pharmacology*; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001562:Benzimidazoles / Q000494:pharmacology*; D005060:Europe; D005260:Female; D005449:Fluorenes / Q000494:pharmacology*; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D006526:Hepatitis C / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012254:Ribavirin / Q000494:pharmacology*; D000069474:Sofosbuvir / Q000494:pharmacology*; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D005449:Fluorenes; C586541:ledipasvir; D012254:Ribavirin; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000069474:Sofosbuvir
keywords: DAA; antiviral therapy; hepatitis C virus; liver transplantation; reinfection; ribavirin; sofosbuvir/ledipasvir