studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 209A
3
Determinants and impact of early viral kinetics in
patients with HCV-recurrence after liver transplantation
treated by sofosbuvir + daclatasvir: results from the
ANRS CO23 CUPILT study
Camille Herve 1 , Audrey Coilly 2 , Claire Fougerou-Leurent 3 , Victor
de Ledinghen 4 , Georges-Philippe Pageaux 5 , Pauline Houssel-Debry
3 , Sylvie Radenne 6 , Christophe Duvoux 7 , Vincent Di
Martino 8 , Nassim Kamar 9 , Louis d’Alteroche 10 , Valerie Canva 11 ,
Pascal Lebray 12 , Jérôme Dumortier 13 , Christine Silvain 14 , Camille
Besch 15 , Danielle Botta-Fridlund 16 , Albert Tran 17 , Helene Montialoux
18 , Emilie Rossignol 3 , Alexandra Rohel 19 , Jean-Charles
Duclos-Vallee 2 , Vincent Leroy 1 ; 1 Gastroenterology, CHU Grenoble,
La Tronche, France; 2 Paul Brousse, Villejuif, France; 3 CHU
Rennes, Rennes, France; 4 CHU Bordeaux, Pessac, France; 5 CHU
Bordeaux, Bordeaux, France; 6 Croix Rousse, Lyon, France; 7 Henri
Mondor, Créteil, France; 8 CHU Besançon, Besançon, France;
9 CHU Toulouse, Toulouse, France; 10 CHU Tours, Tours, France;
11 CHRU Lille, Lille, France; 12 La Pitié Salpétrière, Paris, France;
13 Hôpital Edouard Herriot, Lyon, France; 14 CHU Poitiers, Poitiers,
France; 15 CHU Strasbourg, Strasbourg, France; 16 Conception
Hospital, Marseilles, France; 17 CHU Nice, Nice, France; 18 CHU
Rouen, Rouen, France; 19 ANRS, Paris, France
Early viral kinetic does not seem to impact the chance of SVR12
with the use of new combinations of direct HCV antiviral agents.
However, few data have been reported in HCV-recurrence after
liver transplantation (LT). It could be hypothesized that immunosuppression
might slow down HCV RNA decay. The aims
of our study were to describe in a large cohort of treated LT
patients the HCV RNA kinetics, to identify the predictive factors
of slow response and to evaluate its impact on SVR. Methods:
One hundred and ninety four LT patients prospectively included
in the multi-centric CUPILT cohort and treated by sofosbuvir +
daclatasvir ± ribavirin for 12 or 24 weeks were studied. HCV
RNA was assessed at W0, W2, W4, W8, W12, EOT and
FU12 by real time quantitative PCR with a lower limit of quantification
of 15 IU/ml. Results: The characteristics of patients
were as follows: age: 58.9 ± 8.7 years, baseline HCV RNA:
6.4 log IU/ml, genotype 1: 79%, genotype 3: 11%, treatment
experienced: 47%, HIV co-infection: 7%. The delay between LT
and onset of treatment was 75.8 ± 69.1 months. The majority
(60%) had severe HCV recurrence (F3, F4 or FCH). Immunosuppression
was based on tacrolimus in 62%, cyclosporine in
28% and everolimus in 8% of cases. MMF was administered
in 57% of patients. Treatment duration was 24 weeks in 85%
of cases and 12 weeks in 15% of cases. Ribavirin was used
in 71%) of patients. The percentages of patients with HCV
RNA ≥ 15 IU/ml and HCV RNA < 15 IU/ml but detectable
were distributed as follow: W2: 83% and 13%, W4: 47% and
29%, W8: 13% and 26%, W12 4% and 14%. By multivariate
analysis, independent factors associated with HCV RNA ≥
15 IU/ml at W4 were: use of MMF OR 1.90 (0.99 – 3.66),
p3 treatments.
Intention-to-treat 1- and 5-year overall survival was 84% and
56%, respectively. Among 109 LT recipients, the 1- and 5-year
post-LT survival was 95% and 80%, respectively, after a median
post-LT follow-up of 4.3 years. The Kaplan-Meier probabilities
of treatment failure at 1 and 5 years from first down-staging
procedure were 25% and 44%, respectively. Treatment failure
included dropout due to tumor progression (n=56), liver-related
death without LT (n=12), and HCC recurrence after LT (n=12).
In multivariable Cox proportional hazards regression analy-