title: Sofosbuvir-based antiviral therapy in hepatitis C virus patients with severe renal failure.
abstract: BACKGROUND
  Chronic hepatitis C virus (HCV) infection is the most common chronic liver disease in patients with end-stage renal disease (ESRD). Over the last few years, second-generation direct-acting antivirals have been revolutionary in the treatment of hepatitis C, and sofosbuvir (SOF) is the backbone of most modern treatment strategies. Since SOF is eliminated through the kidney, the aim of this multicentre retrospective study was to assess its antiviral efficacy and safety in HCV-infected patients with severe renal failure [including haemodialysis (HD) patients].
  
  
  METHODS
  Fifty patients (36 males, mean age ± standard deviation 60.5 ± 7.5 years) with chronic HCV infection (G1: 28/56%, cirrhosis: 27/54%) and severe renal failure [i.e. MDRD estimated glomerular filtration rate (eGFR) <35 mL/min], including 35 on HD, were enrolled. Antiviral treatment consisted of SOF/ribavirin (RBV) (n = 7), SOF/RBV/pegylated interferon (n = 2), SOF/daclatasvir ± RBV (n = 30) or SOF/simeprevir ± RBV (n = 11) for 12 or 24 weeks. A reduced dose of SOF (400 mg three times a week or 400 mg every other day) was given to all HD patients. Initial dose of RBV (n = 12) ranged from 400 to 4200 mg/week.
  
  
  RESULTS
  On an intent-to-treat-based analysis, sustained virological response rate was 86% at 12 weeks. During therapy, haemoglobin levels were not significantly modified, but recombinant erythropoietin (rEPO) dose significantly increased in patients treated with RBV. Two patients (4%) required blood transfusion. No patient had treatment discontinuation due to side effects. Dose of RBV was reduced in two patients (16.7%) during antiviral therapy. Dose of SOF was reduced in two non-HD patients because of side effects. In non-HD patients, median eGFR was not significantly modified during treatment.
  
  
  CONCLUSIONS
  Our results strongly suggest that SOF-based antiviral therapy, with a reduced dose of SOF, is safe and effective for the treatment of HCV patients with ESRD, including HD patients.
authors.affiliation: Department of Digestive Diseases, Edouard Herriot Hospital and University of Lyon 1, Hospices Civils de Lyon, Lyon, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Dumortier
authors.affiliation: Department of Hepatogastroenterology, Croix-Rousse Hospital, Hospices Civils de Lyon, Lyon, France.
authors.forename: François
authors.initials: F
authors.lastname: Bailly
authors.affiliation: Department of Hepatogastroenterology and Liver Transplantation, Saint Eloi University Hospital, University of Montpellier, Montpellier, France.
authors.forename: Georges-Philippe
authors.initials: GP
authors.lastname: Pageaux
authors.affiliation: Department of Hepatology, Cochin Hospital, APHP, INSERM UMS-20 Institut Pasteur, Paris, France.
authors.forename: Anaïs
authors.initials: A
authors.lastname: Vallet-Pichard
authors.affiliation: Department of Hepatogastroenterology, Croix-Rousse Hospital, Hospices Civils de Lyon, Lyon, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Radenne
authors.affiliation: Hepatology Unit, Pôle Hépato-digestif, IHU Strasbourg, INSERM U1110, University of Strasbourg, Strasbourg, France.
authors.forename: François
authors.initials: F
authors.lastname: Habersetzer
authors.affiliation: Department of Pharmacology, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France.
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Gagnieu
authors.affiliation: Department of Hepatogastroenterology, Tenon Hospital, Paris, France.
authors.forename: Jean-Didier
authors.initials: JD
authors.lastname: Grangé
authors.affiliation: Department of Hepatogastroenterology, Dijon University Hospital, Dijon, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Minello
authors.affiliation: Department of Digestive Diseases, Edouard Herriot Hospital and University of Lyon 1, Hospices Civils de Lyon, Lyon, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Guillaud
authors.affiliation: Department of Nephrology and Organ Transplantation, Toulouse University Hospital, Université Paul Sabatier, INSERM U1043, IFR-BMT, Toulouse, France.
authors.forename: Nassim
authors.initials: N
authors.lastname: Kamar
authors.affiliation: Internal Medicine-Digestive Department, CHU Purpan, UMR 152, IRD Toulouse 3 University, Toulouse, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Alric
authors.affiliation: Department of Hepatology and Gastroenterology and INSERM U823, CHU A Michallon, Université Grenoble Alpes, Grenoble, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Leroy
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use; D005260:Female; D005919:Glomerular Filtration Rate; D016174:Hepacivirus / Q000187:drug effects*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D051437:Renal Insufficiency / Q000150:complications* / Q000821:virology; D012189:Retrospective Studies; D000069474:Sofosbuvir / Q000627:therapeutic use*
chemical_list: D000998:Antiviral Agents; D000069474:Sofosbuvir
keywords: direct-acting antiviral; haemodialysis; hepatitis C; tolerance; treatment