Sofosbuvir-based treatment of hepatitis C with severe fibrosis (METAVIR F3/F4) after liver transplantation results from the CO23 ANRS CUPILT study

Jerome Dumortier (1) , V. Leroy (2) , C. Duvoux (3) , V. De Lédinghen (4, 5) , C. Francoz (6) , P. Houssel-Debry (7, 8) , S. Radenne (1) , L. d'Alteroche (9) , C. Fougerou-Leurent (7, 8) , V. Canva (10) , V. Di Martino (11) , F. Conti (12) , Nassim Kamar (13, 14) , C. Moreno (15) , P. Lebray (12) , A. Tran (16, 17) , C. Besch (18) , A. Diallo (19) , A. Rohel (19) , E. Rossignol (7) , A. Abergel (20, 21) , D. Botta-Fridlund (22) , A. Coilly (23, 24) , D. Samuel (24, 23) , J.-C. Duclos-Vallée (23, 24) , G.-P. Pageaux (25)

1 Département d'hépatologie
2 Epidémiologie pronostique des cancers et affections graves
3 Service d'Hépatologie, Hôpital Henri Mondor, AP-HP, Créteil, France.
4 Hôpital Haut-Lévêque [CHU Bordeaux]
5 Physiopathologie du cancer du foie
6 CRI (UMR_S_1149 / ERL_8252 / U1149) - Centre de recherche sur l'Inflammation
7 CIC - Centre d'Investigation Clinique [Rennes]
8 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
9 CHU Trousseau [APHP]
10 Service des Maladies de l'Appareil Digestif et de la Nutrition [CHRU Lille]
11 Service d'Hépatologie [CHRU Besançon]
12 UMRS893 - Centre de Recherche Saint-Antoine
13 I2MR - Institut de médecine moléculaire de Rangueil
14 Département de Néphrologie et Transplantation d'organes [CHU Toulouse]
15 ULB - Hôpital Erasme [Bruxelles]
16 CHU Nice - Centre Hospitalier Universitaire de Nice
17 C3M - Centre méditerranéen de médecine moléculaire
18 Service de Transplantation, Centre Hospitalier Universitaire de Strasbourg,
19 Unité de la recherche fondamentale et clinique sur l' hépatite virale, France Recherche Nord & Sud Asdi-VIH Hépatites, Agence Nationale de Recherche sur le Sida
20 CHU Estaing [Clermont-Ferrand]
21 ISIT - Image Science for Interventional Techniques
22 LA CONCEPTION - Hôpital de la Conception [CHU - APHM]
23 Physiopathologie et traitement des maladies du foie
24 Hôpital Paul Brousse
25 Département d'Hépato-Gastroentérologie et de Transplantation Hépatique [CHU Saint-Eloi]

Recurrence of hepatitis C virus (HCV) after liver transplantation (LT) can rapidly lead to liver graft cirrhosis and, therefore, graft failure and retransplantation or death. The aim of the present study was to assess efficacy and tolerance of sofosbuvir (SOF)–based regimens for the treatment of HCV recurrence in patients with severe fibrosis after LT. The Compassionate Use of Protease Inhibitors in Viral C Liver Transplantation (CULPIT) study is a prospective multicenter cohort including patients with HCV recurrence following LT treated with second generation direct antivirals. The present study focused on patients included between October 2013 and November 2014 and diagnosed with HCV recurrence and liver graft extensive fibrosis (METAVIR F3/F4). A SOF-based regimen was administered to 125 patients fulfilling inclusion criteria. The median delay from LT was 95.9 ± 69.6 months. The characteristics of patients were as follows: mean age, 59.4 ± 9.0 years; 78.4% male; infected by HCV genotype 1: 78.2%, mean HCV RNA: 6.1 ± 1.0 log10 IU/mL. Eighty patients had failed previous post-LT antiviral therapy (64.0%) including triple therapy with first generation protease inhibitors in 19 (15.2%) patients. The main combination regimen was SOF/daclatasvir (73.6%). Ribavirin was used in 60 patients. Sustained virological response 12 weeks after treatment was 92.8% (on an intention-to-treat basis); 7 patients with virological failure were observed. Serious adverse events occurred in 25.6% of the patients during antiviral treatment. During antiviral treatment and follow-up, 3 patients were retransplanted and 4 patients died. In conclusion, SOF-based antiviral treatment shows very promising results in patients with HCV recurrence and severe fibrosis after LT. Liver Transplantation 22 1367–1378 2016 AASLD. © 2016 by the American Association for the Study of Liver Diseases

Mots clés: sofosbuvir-based; treatment; hepatitis C virus; transplantation; severe fibrosis (METAVIR F3/F4)

Domaines: Sciences du Vivant [q-bio]; Médecine humaine et pathologie; Hépatologie et Gastroentérologie; Médicaments

Jerome Dumortier, V. Leroy, C. Duvoux, V. De Lédinghen, C. Francoz, et al.. Sofosbuvir-based treatment of hepatitis C with severe fibrosis (METAVIR F3/F4) after liver transplantation results from the CO23 ANRS CUPILT study. Liver Transplantation, 2016, 22 (10), pp.1367--1378. ⟨10.1002/lt.24505⟩. ⟨hal-01397762⟩