This document discusses hepatitis C recurrence after liver transplantation. It notes that hepatitis C recurrence is a major issue, accounting for two-thirds of graft loss. Five years post-transplant, 30% of patients have cirrhosis of the graft. The document examines factors that influence recurrence like fibrosis stage and viral load at one year post-transplant. It also discusses using antiviral treatment before and after transplant to improve outcomes.

1. C.H.B.
Hepatitis C
in Liver Transplantation
Patterns of Recurrence and Therapy
Professor Didier Samuel
Centre Hépatobiliaire,
Inserm Unit 785, Paris XI University
Hopital Paul Brousse, Villejuif, France

2. C.H.B.
With HCCWithout HCC
0
100
200
300
400
500
600
700
800
1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009
Virus Delta Virus B Virus C
0
100
200
300
400
500
600
700
800
1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009
Virus Delta Virus B Virus C
www.eltr.org
HCV
HBV
HDV
INDICATIONS
SURVIVAL
HDV
HBV
HCV
Current Situation of LT for Viral Hepatitis in Europe

3. C.H.B.
LT
Asymptomatic
hepatitis
Acute
Hepatitis
FCH
Chronic
Hepatitis
Chronic
hepatitis
Death
RelT
Cirrhosis
Chronic
Hepatitis
Patient
HCV RNA+
Adapted from Mc Caughan
20%
70%
10%
HCV Recurrence: a Main issue
• HCV recurrence
o Poor outcome, accounting for 2/3 of graft lost
o Five years post-LT, 30% of LT patients have a cirrhosis on the graft
o First cause of mortality

4. McCaughan
J Hepatol 2011
CHOLESTATIC HEPATITIS C

5. C.H.B.
Impact of Fibrosing Cholestatic Hepatitis on Survival
No FCH
FCH 19%
P=0.004
Antonini Am J Transplant 2011

6. Immunosuppression
Proliferation
Apoptosis
Fibrosis
HCV load Inflammation +
IFN- related genes
IFN-
response
-
Acute Rejection
Inflammation
Stress Response
The immune
response
-
+
Pathobiology of Chronic HCV Post LT
McCaughan and Zekry J.Hepatol 2004, Samuel Easl Hepatol 2006
Stimulation of the IMMUNE
RESPONSE by more HCV WINS

7. C.H.B.
• Liver Biopsy
Gold Standard,
Bring additional information than fibrosis stage
. HPVG
Invasive, can be done with liver biopsy
Not routine for many Centres
. Non invasive tests
Biochemical
Elastometry (fibroscan)
. Time post-LT as an adding variable
EVALUATION OF THE SEVERITY OF HCV RECURRENCE

8. Blasco Hepatology 2006; 43: 492-499
HPVG, Fibrosis at 1 Year Post-Transplant and Outcome

9. Gallegos-Orozco Liver Transplant 2009
Fibrosis Stage at 12 months at Liver Biopsy and Survival

10. Carrion Hepatology 2010
Liver Stiffness and Severity of HCV Recurrence

11. Piciotto J Hepatol 2007
Impact of SVR on Survival in Transplant HCV +ve Patients
Berenguer M AJT 2008

12. C.H.B.
Feray J Hepatol 2011
HCV Recurrence: a Main Issue

13. Roche, Samuel Liver Int 2012
Antiviral Treatment Before Transplantation

14. C.H.B.
PegIFN + RBV Before LT
• Treatment PegIFN+RBV until LT
– 47 G1/4/6 patients
» 30 treated
» 17 not treated
• 32 G2/3 patients treated
» 29 treated
» 3 not treated
Everson Hepatology 2012

15. C.H.B.
PegIFN + RBV Treatment Before LT
Everson Hepatology 2012
Meld score: 12, CTP score : 7
Serious Infection rate: 7/59 (12) pts vs 0% control
Death pre-LT: 5/59 vs 2/20 (NS)

16. Antiviral Treatment in Patients Waiting
for Liver Transplantation, Risk of Sepsis Related to CPT
Carrión JA et al. J Hepatol. 2009;50:719-28.

17. C.H.B.Hezode J Hepatol 2013
Risk Factors of Death and Severe infections in cirrhotics
on Triple therapy with Boceprevir or Telaprevir
The Cupic Study

18. Curry Gastro 2015
Sofosbuvir + Riba in Patients with HCC on the waiting List

19. Curry Gastro 2015
Sofosbuvir + Riba in Patients with HCC on the Waiting List
Post-Transplant SVR in those HCV RNA Negative at LT

20. Curry Gastro 2015
Sofosbuvir + Riba in Patients on the Waiting List
Recurrence Related to the Duration of HCV Indetectability Pre-LT

21. • 108 patients randomised 1:1 to 12 or 24 weeks of treatment
• GT 1 or 4 treatment-naïve or -experienced patients with decompensated
cirrhosis (CTP class B [7–9] or C [score 10–12]*)
• Broad inclusion criteria
– No history of major organ transplant, including liver
– No hepatocellular carcinoma (HCC)
– Total bilirubin ≤10 mg/dL, Hb ≥10 g/dL
– CrCl ≥40 mL/min, platelets >30,000/mm3
Flamm S, et al. AASLD 2014; Oral #239.
LDV/SOF + RBV for 12 weeks is not an EMA-recommended treatment regimen;
*Patients with CTP scores 13–15 excluded; CrCl: creatinine clearance;
EMA: European Medicines Agency
SOLAR-1: LDV/SOF + RBV in Decompensated Cirrhosis
Wk 0 Wk 12 Wk 36Wk 24
SVR12N=53
SVR12N=55 LDV/SOF + RBV
LDV/SOF + RBV

22. Flamm S, et al. AASLD 2014; Oral #239.
LDV/SOF + RBV for 12 weeks is not an EMA-recommended treatment regimen;
Error bars represent 90% confidence intervals;
TE: treatment-experienced; TN: treatment-naïve
SOLAR-1: LDV/SOF + RBV in Decompensated Cirrhosis
87 8689 90
0
20
40
60
80
100
CTP B CTP C
SVR12(%)
26/30 19/22 18/2024/27
LDV/SOF + RBV 12 weeks LDV/SOF + RBV 24 weeks
SVR rates were similar with 12 or 24 weeks of LDV/SOF + RBV
Virological response was associated with improvements in bilirubin, albumin, MELD and CTP
scores in both CTP class B and C patients
Prospective, multicentre study of 12 or 24 weeks of LDV/SOF + RBV in TN and TE HCV
GT 1 and 4 patients with CTP B (N=59) or CTP C (N=49) clinically decompensated cirrhosis

23. Flamm S, et al. AASLD 2014; Oral #239.
LDV/SOF + RBV for 12 weeks is not an EMA-recommended treatment regimen
*Missing FU-4: n=2 CTP B 12 wk; n=4 CTP B 24 wk; n=2 CTP C 12 wk;
n=7 CTP C 24 wk; BL: baseline; FU: follow-up
SOLAR-1: LDV/SOF + RBV in decompensated cirrhosis:
Change in MELD from BL to Week 4
(-8)
-6
-4
-2
0
2
4
-6
-4
-2
0
2
4
n=5 n=5 n=2 n=3
(+10)
CTP B CTP C
12 wk (n=30)* 24 wk (n=29)* 12 wk (n=23)* 24 wk (n=26)*

24. Efficacy before LT  Excellent results in compensated cirrhotic patients
 Lower efficacy in decompensated ones
Approved regimens
RBV RBV
ALLY
RBV RBV Δ
88%
82%
94%
72%
SOF+LDV (1) SOF+DCV (2) 3D (3) SOF+SIM (4)
Compensated
Child<11
(1) Charlton M. Gastroenterology 2015; (2) Poordad F, Etats-Unis, EASL 2015, Abs. L08; (3) Poordad F, Etats-Unis, EASL 2014, Oral late
breaker LB O163 (4) Reddy R, Etats-Unis, EASL 2015, Abs. O007

25. Efficacy before LT
 SVR12 depends on severity of cirrhosis
o Using SOF+LDV or 3D, low platelets count and low
albumin level are risk factors of relapse
RBV RBV
ALLY
RBV RBV Δ
88%
82%
94%
72%
SOF+LDV (1) SOF+DCV (2) 3D (3) SOF+SIM (4)
Compensated
(1) Charlton M. Gastroenterology 2015; (2) Poordad F, Etats-Unis, EASL 2015, Abs. L08; (3) Poordad F, Etats-Unis, EASL 2014, Oral late
breaker LB O163 (4) Reddy R, Etats-Unis, EASL 2015, Abs. O007

26. Efficacy before LT
SVR12 depends also on genotype
RBV RBV
ALLY
RBV RBV Δ
80
86
59
89
71
81
43
0
74
82
70
85
73
60
71
1…
0
20
40
60
80
100
SVR12%(ITT)
252 28 172 15 164 21 45 5 61 7 114 7 27 13 3
SOF + LDV + RBV SOF + LDV SOF + DCV + RBV SOF + DCV
Overall Genotype 1 Genotype 3 Others
p < 0,05
Foster G, UK, EASL 2015, Abs. O002
Combinaison SOF and NS5A inhibitor + RBV during 12 weeks
467 cirrhotic patients Child ≥ B7

27. Next Generation: Is this going to change?
Astral 4: Sofobuvir + Velpatasvir
Ribavirin still required in most cirrhotic patients
Curry NEJM 2016

28. Safety before LT  Good safety profile
 SAE rate of 20% (mainly due to RBV)
 Hepatic function is one issue
1. Ouwerkerk-Mahadeva S, et al. AASLD 2013. Oral #65; 2. Gilead Sciences Europe. SOVALDI (sofosbuvir), Summary of Product
Characteristics, January 2014; 3. German P, et al. AASLD. 2013. Oral #52; 4. Khatri A, et al. AASLD. 2012. Oral #66; 5. Bifano M, et al.
AASLD. 2011. Oral #78.
Pharmacokinetic changes according to liver function
Hepatic function impairment Avoid
Mild Moderate Severe
Simeprevir1 + 2.44 + 5.22 Child C
Sofosbuvir2 + 1.26 + 1.43
Ledipasvir3 No adjustement
Paritaprevir/r4 - 0.71 + 1.62 + 10.23 Child C
Ombitasvir4 + 0.92 + 0.70 + 0.45
Dasabuvir4 + 1.17 + 0.84 + 4.19 Child C?
Asunaprevir5 - 0.79 + 9.8 + 32 Child B/C
Daclatasvir5 - 0.57 - 0.62 - 0.64

29. Decompensated Cirrhosis
Is Delisting Possible?
Baseline
MELD < 15
(n = 199)
Patients(%)
0
10
20
-16
0
-11 -9 -8 -7 -6 -5 -4 -3 -2 -1 0 1 2 3 4 7 8 9 12 13
Deterioration : 26 %
0 0
Improvement: 56 %
<1
2 3 3
8 8
15
17 18
13
7
2 1 <1 1<1 <1<1
Baseline
MELD ≥ 15
(n = 72)
Patients(%)
0
10
20
-16 -11 -9 -8 -7 -6 -5 -4 -3 -2 -1 0 1 2 3 4 7 8 9 12 13
Deterioration : 11 %Improvement : 76 %
5
2
3
11
10
16
8
14
13
5
0
3 3
0 00 00
5
22
Gane EJ, New Zealand, AASLD 2015, Abs. 1049
Variations of MELD score Baseline/EOT in SOLAR I and II studies among Child>B cirrhotics

30. Association Between Improvement and SVR
Munoz J, USA, AASLD 2015, Abs. 202
Only 28% had an improvement in the MELD score ≥ 3 points
DeltaMELD
+10
+15
56 %+5
0
-5
-10
-15
-20
20 % 23 %
0
20
All MELD
improvement
No change MELD
deterioration
40
60
80
100
SVR12(%)
 Some patients improve without achieving SVR
 Although achieving SVR, some patients worsen
(comorbidities?)
Meta-analyses of 5 studies

31. Is there a Point
of no Return?
 National cohort study in patients waiting for LT in
France
 SVR12 = 88 %
183 patients
ESLD without
HCC
N=77
LT
31%
Delisting for
improvement
16%
HCC
N=106
LT
54%
Drop-out
6%
Coilly A, France, AASLD 2015, Abs. 95

32. 7.5
AUC: 0.814
Child-
Pugh
score
MELD
score
Complete improvement
No response
Partial improvement
Is there a Point of no return?
 National cohort study in patients waiting for LT in France: SVR12 = 88 %
Coilly A, France, AASLD 2015, Abs. 95
36%
28%
36%
Cirrhosis, n=53
21% Child B
25% Child C
72% Child A
MELD score could not be the good
marker

33. Taking into account the
System of Organs
Allocation
Deaceased donor
Male 61 yo, G1b
ESLD without HCC
MELD 23 after SBP
Listed for LT
National allocation system

34. Taking into account the
system of organs allocation
Deaceased donor
Male 61 yo, G1b
ESLD without HCC
MELD 23 after SBP
Listed for LT
Ascites
Covert HE
LT still indicates but no more
access…
National allocation system
HCV treatment

35. C.H.B.
o Antiviral treatment with Peg-IFN+RBV
 Treatment done at the stage of chronic hepatitis
 Peg-IFN +RBV = standard of care:
 Overall SVR: 30%;
 SVR G1: 25- 30%, SVR G3: 50% (Berenguer J Hepatol
2008, Calmus J Hepatol 2012)
 EPO in 40% of patients
 Poor tolerance of treatment when F3-F4 (Carrion Gastro
2007, Roche LT 2008): 30% of premature discontinuation
HCV Treatment after LT
Standard of Care Until 2012

36. C.H.B.
Coilly AAC 2012
Coilly J Hepatol 2014
First Generation Protease inhibitors in HCV Recurrence
Boceprevir and Telaprevir

37. C.H.B.
Coilly Plos One 2015
First Generation Protease inhibitors in HCV Recurrence
Boceprevir and Telaprevir

38. C.H.B.Coilly Plos One 2015
First Generation Protease inhibitors in HCV Recurrence
Boceprevir and Telaprevir

39. C.H.B.
Triple Therapy with Telaprevir or Boceprevir
The Crush Study
Burton J Hepatol 2014
Tolerance
Anemia < 10 : 78%
Blood Transfusion: 57%
EPO: 81%
GCSF: 41%
Creat 0.5 mg/l : 38%
Rash: 11%
Hospitalizations for infection: 11%
Discontinuation: 15%
Deaths : 9%

40. C.H.B.
Triple Antiviral Therapy with Telaprevir in HIV-HCV
Liver Transplant Recipients
Antonini et al. AIDS 2013

41. C.H.B.
The Advent of Second Generation DAAs
After Liver Transplantation

42. C.H.B.
PegIFN +RBV+Daclatasvir for FCH after LT
Fontana Liver Transpant 2012

43. C.H.B.
Sofosbuvir+Daclatasvir for FCH after LT
Fontana Am J Transplant 2013

44. C.H.B.
Sofosbuvir + Ribavirin After Transplantation
Charlton Gastro 2015
SOF 400 mg + RBV 400‒1200 mg (N=40) SVR12
• Patients with recurrent HCV post-liver transplant
– Liver transplant ≥6 and ≤150 months prior to enrollment
– Any HCV genotype
– Naïve or treatment-experienced
– CTP ≤7 and MELD ≤17
• Low, ascending-dose RBV regimen starting at 400 mg/day,
escalated based on hemoglobin levels

45. C.H.B.
Sofosbuvir + Ribavirin After Transplantation
Charlton AASLD 2013
SOF + RBV (N=40)
Male, n (%) 31 (78)
Median age, y (range) 59 (49-75)
White, n (%) 34 (85)
BMI <30 kg/m2, n (%) 30 (75)
Mean HCV RNA log10 IU/mL (range) 6.55 (4.49-7.59)
Genotype, n (%)
1a
1b
2
3
4
22 (55)
11( 28)
0
6 (15)
1 (3)
IL28B, n (%)
CC
CT
TT
13 (33)
16 (40)
11 (28)
Metavir-equivalent fibrosis stage, n (%)
None or minimal (F0)
Portal Fibrosis (F1-F2)
Bridging Fibrosis (F3)
Cirrhosis (F4)
1 (3)
14 (35)
9 (23)
16 (40)
Prior HCV Treatment, n (%) Yes 35 (88)
Median years since liver transplantation (range) 4.3 (1.02-10.6)

46. C.H.B.
Sofosbuvir + Ribavirin After Transplantation
Charlton Gastro 2015

47. C.H.B.
Sofosbuvir + Ribavirin After Transplantation
Tolerance
Charlton AASLD 2013 and Gastro 2015
0.8
0.9
1.0
1.1
1.2
10
11
12
13
14
15
0 1 2 3 4 8 12 16 20 24 FU-2 FU-4
Hb
Creatinin
SAE: 15%, SAE leading to discontinuation: 5%, fatique 30%,
Hb< 10g:/dl: 33%; Hb< 8g: 3%, 20% Received EPO

48. C.H.B.
Compassionate Use Sofosbuvir + Ribavirin ± PegIFN
in Liver Transplant Patients
X Forns Hepatology 2015

49. C.H.B.
Compassionate Use Sofosbuvir + Ribavirin ± PegIFN
in Liver Transplant Patients
X Forns
Hepatology
in press 2015

50. C.H.B.
Compassionate Use Sofosbuvir + Ribavirin ± PegIFN
in Transplant Patients: Virologic Response
X Forns Hepatology In Press 2015

51. C.H.B.
Compassionate Use Sofosbuvir + Ribavirin ± PegIFN
in Transplant Patients: Virologic Response: Clinical Outcome
X Forns Hepatology 2015

52. ABT450/Ritonavir/Ombitasvir + Dasabuvir + RBV in LT
Recipients with Recurrent HCV GT 1
• Phase II Study on efficacy and tolerance of ABT-450/r/ombitasvir
150 mg/100m g/25 mg/d + dasabuvir 250 mg x 2/d in patients
with HCV reinfection post-LT
• Patients G1, fibrosis ≤ F2 at Liver biopsy, no prior PEG/RBV after LT
• Dosing RBV free for the investigator
• CNI adaptation
– Tacrolimus 0.5 mg/week or 0.2 mg/3 days
– Ciclosporine 1/5 of initial daily dosing once a day
3D + RBV
(n = 34)
SVR12
D0 W24 W72
Kwo P, Etats-Unis, EASL 2014, Abs. O114 actualisé

53. C.H.B.
ABT450/Ritonavir/Ombitasvir + Dasabuvir + RBV in LT Recipients
with Recurrent HCV GT 1
P Kwo NEJM 2015

54. 12 or 24 weeks LDV/SOF + RBV after LT: Solar 1 study
Excellent results in F0-F3 Patients
F0–F3
SVR12(%)
53/55 22/26 15/18
CTP B
55/56 25/26 24/25 2/3
CTP A
LDV/SOF + RBV 12 weeks LDV/SOF + RBV 24 weeks
3/5
CTP C
SVR rates were similar with 12 or 24 weeks of LDV/SOF + RBV
Charlton et al, Gastroenterology 2015

55. Sofosbuvir + Daclatasvir After LT-The Cupilt Study
• Decision of investigator
Week 0 Week 12 Week 24 Week FU12
SOF=400mg/day; DCV=60mg/day; RBV=decision of physician according to renal function
SOF+DCV
SOF+DCV+RBV
SOF+DCV+RBV
SOF+DCV
n=11
n=3
n=52*
n=64*
Coilly et al, EASL 2015

56. Sofosbuvir + Daclatasvir After LT-The Cupilt Study
Virological Kinetics
Coilly et al, EASL 2015
 Mean time to achieve undetectability: 5.7±3.3 weeks [1-20]
0
1
2
3
4
5
6
7
8
0 4 8 12 16 20 24
HCVRNA(logIU/mL)
Week
SOF+DCV (n=75)
SOF+DCV+RBV (n=55) p=ns

57. Sofosbuvir + Daclatasvir After LT-The Cupilt Study
SVR according to Treatment Duration
Coilly et al, EASL 2015
100%
67%
100% 98%100%
67%
97% 96%
SOF+DCV (n=11) SOF+DCV+RBV (n=3) SOF+DCV (n=64) SOF+DCV+RBV (n=52)
Week 12 Week 24
EOT SVR12
Virological
breakthrough n=1
Lost of FU n=1
Relapse n=1
Death n=2
Wk1 & FU Wk6
p=ns

58. Sofosbuvir + Daclatasvir After LT-The Cupilt Study
Overall Tolerability
Coilly et al, EASL 2015
• One death at week 1: hyperosmolar coma in a patients with a previous history of diabetes
mellitus
• One death at week 6 post-treatment: HCC recurrence (HCV RNA negative)
• 4 cardiac disorders: 2 High Blood Pressure, 2 cardiac decompensations in patients with past
history of cardiomyopathy
Overall (n=130) SOF+DCV (n=75)
SOF+DCV+RBV
(n=55)
p
Serious adverse
events
30 (23.1) 15 (20.0) 15 (27.3) ns
Death 2 (1.5) 0 (0) 2 (3.6) ns
Cardiac disorders 4 (3.0) 1 (1.3) 3 (5.5) ns
Biopsy proven acute
rejection
2 (1.5) 1 (1.3) 1 (1.8) ns
Infections (G3/4) 9 (6.9) 3 (4) 6 (10.9) ns

59. Sofosbuvir + Daclatasvir After LT-The Cupilt Study
Hematological Adverse Events
Coilly et al, EASL 2015
Overall (n=130) SOF+DCV (n=75) SOF+DCV+RBV (n=55)
Anaemia 49 (37.7) 17 (22.6) 32 (58.2)
Grade 0 (but EPO) 7 (5.3) 1 (1.3) 6 (11.0)
Grade 3/4 (<8 g/dL) 18 (13.8) 6 (8.0) 12 (21.8)
Erythropoietin use 30 (23.1) 9 (12.0) 21 (38.2)
Blood transfusion 13 (10.0) 5 (6.7) 8 (6.2)
RBV reduction for AE 25 (19.2) - 25 (45.5)
Neutropenia 35 (27) 13 (17.3) 22 (40)
Grade 3/4 (<0.75G/L) 8 (6.2) 1 (1.3) 7 (12.8)
G-CSF use 2 (1.6) 1 (1.3) 1 (1.8)
Thrombocytopenia 37 (28.5) 20 (26.7) 17 (30.1)
Grade 3/4 (<50G/L) 7 (5.4) 3 (4.0) 4 (7.3)

60. Efficacy after LT  Most regimens allow to achieve a SVR12 rate of
>90%
Approved regimens
70%
95% 94% 95% 90%
SOF+RBV (1) SOF+LDV (2) SOF+DCV (3,4) 3D (5) SOF+SIM (6,7)
RBV RBV
ALLY
RBV RBV Δ
(1) Charlton M, Gastroenterology, 2015; (2) Charlton M, Gastroenterology, 2015; (3) Coilly A, EASL G15, 2015; (4) Poordad F, Etats-Unis, EASL 2015, Abs. L08; (5)
Kwo py, NEJM, 2014; (6) Pungpapong S, Hepatology 2015. (7) Reddy R, Etats-Unis, EASL 2015, Abs. O007

61. Leroy et al, Clin Gastroenterol Hepatol 2015
Impressive Efficacy in FCH Transplant Patients
Sofosbuvir + Daclatasvir or Sofosbuvir + Ribavirine
in 23 Patients with FCH-The Cupilt Cohort

62. Leroy et al, Clin Gastroenterol Hepatol 2015
Sofosbuvir + Daclatasvir or Sofosbuvir + Ribavirine
in 23 Patients with FCH-The Cupilt Cohort
Impressive Efficacy in FCH Transplant Patients

63. Compassionate use of Sofosbuvir + Ribavirine +- Peg IFN After LT-
Clinical outcome
Forns et al, Hepatology 2015
Efficacy Lower in Transplant Patients
with Advanced Cirrhosis

64. Ciclosporine Tacrolimus
Sofosbuvir
Sofosbuvir/Ledipasvir
Ciclosporine AUC - 2% Tacrolimus AUC + 13%
Daclastavir
Simeprevir
Ciclosporine AUC +4.74 Tacrolimus AUC +79%
Ombitasvir, paritaprevir, ritonavir,
dasabuvir
Ciclosporine AUC +5.82
Dosage ÷5
Tacrolimus AUC +57.1
0.5mg/wk ou 0.2mg/2days
Safety after LT  Good safety profile
 SAE rate of 20% (mainly due to RBV)
 Issue: drug-drug interactions
Coilly, A. Liver Int. 2015

65. Safety after LT  Good safety profile
 SAE rate of 20% (mainly due to RBV)
 Issue: drug-drug interactions
Coilly, A. France, G15, EASL 2015.
ANRS C023 CUPILT cohort: SOF+DCV
Tacrolimus Ciclosporine Everolimus MMF
Number of patients 78 37 13 71
Number who
changed dosage –
n (%)
44 (56 %) 18 (49 %) 5 (38 %) 9 (13 %)
 Most changes occurred after 4 weeks of treatment, reflecting improvement in liver
function more than clinically relevant drug-drug interactions
 To monitor immunosuppressive drugs is still mandatory

66. C.H.B.
SVR with DAA in LT Patients
Gamballi J Hepatol 2014

67. C.H.B.
CONCLUSION
• The Field of Liver Transplantation In HCV Patients is moving
dramatically with IFN-free regimen
• Some questions are open:
– Treat before or after Transplantation?
– Remove patients from the waiting list?
– Which combination?
– Duration of treatment ? Use of RBV?
– How to avoid relapse? Risk of liver failure in case of relapse?
• The survival after transplantation for HCV infection will improve

68. Conclusion 3: Management Proposal
Treatment with DAA Before or After LT
Patients on waiting list
HCC
Child A/B
Treat before LT
Child C
Consider
benefits
To control
HCC: Treat
Reduced
access to LT:
Delay
ESLD – No HCC
Child B
Consider
MELD score
Low: Treat High: Delay
Child C
Treat after LT

69. Take Home Messages
 Treat hepatitis C using DAA before or after LT? Both strategies
are feasible with excellent efficacy results and good safety
profiles
 Regarding efficacy, better results are achieved after LT than
before in decompensated cirrhotic patients
 Regarding safety, drug-drug interactions and degree of hepatic
impairment are still issues, and favor the use of NS5A inhibitors
 Withdraw patients of waiting list is feasible and should concern
about 30% of patients.

70. Centre Hépato-Biliaire
A Coilly
E De Martin
F Chiappini
B Roche
R Sobesky
F Saliba
T Antonini
JC Duclos-Vallée
And all the Team at The CHB