Sofosbuvir-based antiviral therapy in hepatitis C virus patients with severe renal failure

Jérôme Dumortier (1) , François Bailly (2) , Georges-Philippe Pageaux (3) , Anaïs Vallet-Pichard (4) , Sylvie Radenne (2) , François Habersetzer (5, 6) , Marie-Claude Gagnieu (7) , Jean-Didier Grangé (8) , Anne Minello (9) , Olivier Guillaud (1) , Nassim Kamar (10, 11) , Laurent Alric (12, 13) , Vincent Leroy (14, 15)

1 Service d'hépatogastroentérologie [Hôpital Edouard Herriot, Hospices Civils de Lyon]
2 Service d'hépatogastroentérologie [Hôpital de la Croix-Rousse, Hospices Civils de Lyon]
3 Département d'Hépato-Gastroentérologie et de Transplantation Hépatique [CHU Saint-Eloi]
4 Département d'hépatologie [CHU Cochin]
5 IVH - Institut de Recherche sur les Maladies Virales et Hépatiques
6 Pôle Hépato-digestif
7 Hospices Civils de Lyon, Groupement Hospitalier Edouard Herriot, Laboratoire de Biochimie et Biologie Moléculaire, Lyon, France
8 CHU Tenon [AP-HP]
9 Service d'Hépato-Gastro-Entérologie (CHU de Dijon)
10 CPTP - Centre de Physiopathologie Toulouse Purpan
11 Département de Néphrologie et Transplantation d'organes [CHU Toulouse]
12 Service Médecine interne [CHU Toulouse]
13 PHARMA-DEV - Pharmacochimie et Biologie pour le Développement
14 INSERM U823 - Institut d'oncologie/développement Albert Bonniot de Grenoble
15 Service d'hépato-gastroentérologie [CHU Grenoble Alpes]

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.

Mots clés: direct-acting antiviral; haemodialysis; hepatitis C; tolerance; treatment

Domaines: Urologie et Néphrologie

Jérôme Dumortier, François Bailly, Georges-Philippe Pageaux, Anaïs Vallet-Pichard, Sylvie Radenne, et al.. Sofosbuvir-based antiviral therapy in hepatitis C virus patients with severe renal failure. Nephrology Dialysis Transplantation, 2017, 32 (12), pp.2065-2071. ⟨10.1093/ndt/gfw348⟩. ⟨hal-01689582⟩