Multicentre experience using daclatasvir and sofosbuvir to treat hepatitis C recurrence - The ANRS CUPILT study.
HCV recurrence remains a major issue in the liver transplant field, as it has a negative impact on both graft and patient survival. The purpose of this study was to investigate the efficacy and safety of treating HCV recurrence with sofosbuvir (SOF) and daclatasvir (DCV) combination therapy.



From October 2013 to March 2015, 559 liver recipients were enrolled in the prospective multicentre France REcherche Nord&Sud Sida-hiv Hépatites (ANRS) Compassionate use of Protease Inhibitors in viral C Liver Transplantation cohort. We selected 137 patients with an HCV recurrence receiving SOF and DCV, whatever the genotype or fibrosis stage. The use of ribavirin and the duration of therapy were at the investigator's discretion. The primary efficacy end point was a sustained virological response (SVR) 12weeks after the end of treatment.



The SVR rate 12weeks after completing treatment was 96% under the intention-to treat analysis and 99% when excluding non-virological failures. Only two patients experienced a virological failure. The serious adverse event (SAE) rate reached 17.5%. Four patients (3%) stopped their treatment prematurely because of SAEs. Anaemia was the most common AE, with significantly more cases in the ribavirin group (56% vs. 18%; p<0.0001). A slight but significant reduction in creatinine clearance was reported. No clinically relevant drug-drug interactions were noted, but 52% of patients required a change to the dosage of immunosuppressive drugs.



Treatment with SOF plus DCV was associated with a high SVR12 and low rates of serious adverse events among liver recipients with HCV recurrence.



The recurrence of hepatitis C used to be the first cause of graft failure in infected liver transplanted recipients. Our study demonstrates the great efficacy of one combination of new all-oral direct-acting antiviral, sofosbuvir and daclatasvir, to treat the recurrence of hepatitis C on the graft. Ninety-six per cent of recipients were cured. The safety profile of this combination seemed to be good, especially no relevant drug-drug interaction with immunosuppressive drugs.
AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif F-94800, France; Université Paris Sud, Université Paris Sud-Saclay, UMR-S 1193, Villejuif F-94800, France; INSERM, Unité 1193, Villejuif F-94800, France; DHU Hepatinov, Villejuif F-94800, France. Electronic address: audrey.coilly@aphp.fr.
Audrey
A
Coilly
Hôpital Universitaire de Pontchaillou, Service de Pharmacologie, Rennes, France; INSERM, CIC 1414 Clinical Investigation Centre, Rennes, France.
Claire
C
Fougerou-Leurent
Service d'Hépato-Gastroentérologie, Hôpital Haut-Lévêque, CHU Bordeaux, & INSERM U1053, Bordeaux, France.
Victor
V
de Ledinghen
Hôpital Universitaire de Pontchaillou, Service d'Hépatologie et Transplantation Hépatique, Rennes, France.
Pauline
P
Houssel-Debry
Service d'Hépatologie, Hôpital Henri-Mondor, AP-HP, 94000 Créteil, France.
Christophe
C
Duvoux
Service d'Hépatologie, CHRU Jean Minjoz et Université de Franche-Comté, Besançon, France.
Vincent
V
Di Martino
Service d'Hépatologie, HCL, Hôpital de la Croix-Rousse, 69205 Lyon, France.
Sylvie
S
Radenne
Département de Néphrologie et Transplantation d'Organes, CHU Rangueil, INSERM U1043, IFR-BMT, Université Paul Sabatier, Toulouse, France.
Nassim
N
Kamar
Service Hépato-gastro-entérologie, CHU Tours, France.
Louis
L
D'Alteroche
Clinique Universitaire d'Hépato-Gastroentérologie, Pôle Digidune, CHU de Grenoble, France.
Vincent
V
Leroy
CHRU de Lille, Service d'Hépatologie, Hôpital Huriez, CHRU Lille, 59037 Lille, France.
Valérie
V
Canva
Service d'Hépatologie et de Transplantation Hépatique, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
Pascal
P
Lebray
Département de Gastroenterologie, d'Hépatopancréatologie et Cancérologie Digestive, CUB Hôpital Erasme, Université Libre de Bruxelles, Bruxelles, Belgium.
Christophe
C
Moreno
Unité de Transplantation Hépatique, Fédération des Spécialités Digestives, Hôpital Edouard Herriot, Hospices Civils de Lyon et Université Claude Bernard Lyon 1, Lyon, France.
Jérôme
J
Dumortier
Service Hépato-gastro-entérologie, CHU Poitiers, France.
Christine
C
Silvain
Centre de Chirurgie Digestive et Transplantation Hépatique, Université de Strasbourg, France.
Camille
C
Besch
Service de MPU Infectiologie CHD Vendée, 85925 La Roche sur Yon, France.
Philippe
P
Perre
CHU Timone, Service d'Hépato-gastroentérologie, Marseille F-13005, France.
Danielle
D
Botta-Fridlund
Hôpital universitaire de Nice, Service d'Hépato-gastroentérologie, INSERM, U1065, Equipe 8, Université de Nice-Sophia-Antipolis, Faculté de Médecine, Nice F-06107, Cedex 2, France.
Rodolphe
R
Anty
Service d'Hépatologie, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy, France.
Claire
C
Francoz
Service d'Hépato-gastroentérologie, CHU Estaing Clermont-Ferrand, Clermont-Ferrand, France.
Armando
A
Abergel
Service d'Hépato-gastroentérologie, CHU Limoges, Limoges, France.
Maryline
M
Debette-Gratien
Service d'Hépatologie et de Transplantation Hépatique, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
Filomena
F
Conti
Hôpitaux Universitaires de Strasbourg, Inserm U 1110, LabEx HepSYS, Université de Strasbourg, Strasbourg, France.
François
F
Habersetzer
Unité de recherché Clinique et Fondamentale sur les Hépatites Virales, Agence Nationale de Recherche sur le Sida et les Hépatites Virales, Paris, France.
Alexandra
A
Rohel
Hôpital Universitaire de Pontchaillou, Service de Pharmacologie, Rennes, France; INSERM, CIC 1414 Clinical Investigation Centre, Rennes, France.
Emilie
E
Rossignol
Hôpital Universitaire de Pontchaillou, Service de Pharmacologie, Rennes, France; INSERM, CIC 1414 Clinical Investigation Centre, Rennes, France.
Hélène
H
Danjou
AP-HP Hôpital Paul-Brousse, Service de Virologie, Villejuif F-94800, France; Université Paris Sud, Université Paris Sud-Saclay, UMR-S 1193, Villejuif F-94800, France; INSERM, Unité 1193, Villejuif F-94800, France; DHU Hepatinov, Villejuif F-94800, France.
Anne-Marie
AM
Roque-Afonso
AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif F-94800, France; Université Paris Sud, Université Paris Sud-Saclay, UMR-S 1193, Villejuif F-94800, France; INSERM, Unité 1193, Villejuif F-94800, France; DHU Hepatinov, Villejuif F-94800, France.
Didier
D
Samuel
AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif F-94800, France; Université Paris Sud, Université Paris Sud-Saclay, UMR-S 1193, Villejuif F-94800, France; INSERM, Unité 1193, Villejuif F-94800, France; DHU Hepatinov, Villejuif F-94800, France.
Jean-Charles
JC
Duclos-Vallée
Département d'Hépato-gastroentérologie et de Transplantation Hépatique, CHU Saint-Eloi, Université de Montpellier, Montpellier F-34295, France.
Georges-Philippe
GP
Pageaux
D000998:Antiviral Agents; D057176:Compassionate Use Trials; D004359:Drug Therapy, Combination; D005602:France; D016174:Hepacivirus; D006526:Hepatitis C; D006801:Humans; D011446:Prospective Studies; D012254:Ribavirin; D000069474:Sofosbuvir; D016896:Treatment Outcome
D000998:Antiviral Agents; D012254:Ribavirin; D000069474:Sofosbuvir
Daclatasvir; Direct-acting antiviral agents; Hepatitis C; Liver transplantation; Recurrence; Sofosbuvir