Conf about LT in HIV patient presented at IHPBA 2016 in Sao Paulo

1. Liver Transplantation in the setting
of HIV infection
Eric Vibert, MD, PhD
Hopital Paul Brousse, AP/HP
Villejuif, France

2. Summary
• Epidemiology of liver disease in HIV+ patient
• Why liver transplantation is feasible HIV+ patient ?
• Result of LT in HIV for End-Stage Liver Disease
– Impact of new treatment of HVC
• Result of LT in HIV for Hepatocellular Carcinoma
• Retransplantation in HIV patient

3. Epidemiology of liver disease in
HIV patient

4. 1996 : Highly Active Anti-Retroviral
Therapy (HAART) in HIV patients
Giordano et al. Arch Int Med 2008
HIV/HCV
HIV
HIV/HCV
HIV
Incidence of Cirrhosis before 1996
3.4% 6.1%
Incidence of Cirrhosis after 1996
1991 – 2000 : 16 439 HIV in US Veteran Database with or with HVC

5. Rate of ELD and HCC in HIV/HVC
Ioannou et al. Hepatology 2013
6% of End-Stage Liver Disease 1.6% of Hepatocellular carcinoma
Stable incidence from 2004 Increasing incidence from 2004
1996 to 2009 : Incidence of cirrhosis and HCC in VIH pts in US Database (n=24040 in 2009)

6. Why LT is feasible in HIV ?

7. Survival is dependent of MELD Score and not HIV status
1999 to 2005 : 35 HIV/HVC coinfected patients transplanted
2008

8. Similar mortality on waiting list in HIV
patients listed without HCC in US
2003 – 2007 : 20 transplant centers in US : 167 HIV+ matched with 792 HIV-
Time to Death Time to Transplant
Subramanian et al. Gastroenterology 2010
CD4+ cells > 100/µL and HIV RNA < 50 copies/ml

9. Subramanian et al. Gastroenterology 2010

10. Indication of LT in 132 HIV+ Patients
in Paul Brousse Hospital, France
Indication of Liver Transplantation N (%)
HVC Cirrhosis 82 (62%)
Hepatocellular Carcinoma 26 (19%)
HVB Cirrhosis 9 (7%)
Vascular Liver Disorder (Nod Reg Hyperplasia) 5 (4%)
Fulminant Hepatitis 4 (3%)
Others 6 (4.5%)
Period 1998-2015 : 132 / 1893 LT (7%) on HIV+ patients
CD4+ > 200 cell/µL or > 100 cell/µL if portal hypertension
HIV RNA < 50 copies/ml and No opportunistic infection from 1 year

11. No impact of Infection on Survival in
109 HIV+ transplanted patients
4/109 (3.6%) developed opportunistic infection with a
median delay of 16 months (11-23) without mortality
Teicher et al. Transp Inf Dis 2015
85%
81%
63%
57%

12. Cause of 43 deaths after LT
1-year patient mortality : 7%
3-year patient mortality : 33%
5-year patient mortality : 39%
Teicher et al. Transp Inf Dis 2015

13. Pre-LT Status RR (IC95%) p
Psoas Area < 1500 4.8 (1.3 – 17.9) 0.018
MELD > 17 3.9 (1.1 – 14.3) 0.033
HBV vs Non HBV 7.2 (1.1 – 47.7) 0.03
Major impact of Sarcopenia in HIV+
2007 – 2011 : 56 HIV+ patients transplanted (39 ELD and 17 HCC) in Paul Brousse Hospital
Antonini et al. EASL 2013

14. Result of LT in End Stage Liver
disease in HIV patient ?

15. Author
Journal Year n
Survival (%)
1yr 3 yrs
Fung et al.
Liver Transplant 2004
3 100
-
Norris et al.
Liver Transplant 2004
4 100
-
Duclos-Vallée et al.
J Hepatol 2006
5 100
-
Schreibman et al.
Transplantation 2007
8 75
-
Roland et al.
Am J Transplant 2007
5 100
-
Tateo, et al.
AIDS 2009
13
100
Author
Journal Year n
Survival (%)
3 yrs 5 yrs
Ragni et al.
J Infect Dis 2003
15 57 -
De Vera et al.
Am J Transpl 2007
27 56 33
Schreibman et al.
Transplantation 2007
15 73 -
Vennrecci et al.
Transpl Proc 2007
12 58 -
Duclos-Vallée et al.
Hepatology 2008
35 73 51
Terrault et al.
Hepatology 2009
81 59 -
Important LT survival difference
HIV/HBV and HIV/HCV
Cooper et al. AIDS 2011
HIV / HBV HIV / HCV

16. Miro et al. J Hepatol 2014
HIV impact survival in LT with HCV
Survival near from the ethical limit of 50% of survival at 5 years

17. Higher rate and more severe
recurrence of HVC after LT in HIV
Progression to Fibrosis after LT for
HVC with or without HIV infection
Duclos-Vallée et al. Hepatology 2008
Very severe HVC recurrence
Fibrosis Cholestatic Hepatitis
(20% FCS in HIV+ vs 5% in HIV-)
No FCH (n=48)
FCH (n=11)
p<0.004
Mean survival : 26 ± 4.7 months
No Survival
Antoni et al. Am J Transp 2011

19. Sofosbuvir-based regimens in 16 HIV/HCV
co-infected patients after liver transplantation:
ANRS CO23 CUPILT study
TM Antonini, A Coilly, E Rossignol, C Fourgerou-Leurent, S Radenne, A Veislinger, D
Botta-Fridlund, F Durand, P Houssel-Debry, N Kamar, V Canva, P Perré, V De Ledinghen,
I Bertucci, A Diallo, J Dumortier, V Leroy, D Samuel, GP Pageaux and JC Duclos-Vallée

20. HCV virological response
13%
40%
73%
81%
100% 100%
94% 94%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100% *
*virological relapse: G1a , SOF/RBV 24W, FCH W: week; SVR: sustained virological response

21. Castells et al. J Hepatol 2015
78 HIV/HCV coinfected patients treated before New HVC treatment
New HVC treatment will drastically
improved result of LT in HVC/HIV
Before New Drugs

22. Results of LT for HCC in HIV patient

23. 1992 to 2006 : 63 patients in 6 centers
Survival are similar and treatment is usefull
2007

24. Higher Rate of Infiltrative HCC in HIV
Lewin et al. Radiology 2015
2008 – 2012 : French multicentric prospective study of 35 HIV/HCV cirrhotic patients with HCC

25. Lewin et al. Radiology 2015

26. Correlation with low CD4 rate and
infiltrative HCC tumor
Lewin et al. Radiology 2015
CD4 < 200 cell/µL without portal hypertension
Not candidate for LT

27. Intent-to-treat result analysis : 21 listed then 16 HIV transplanted for HCC
LT for HCC in HIV+ patient
Vibert et al. Hepatology 2011
2003-2008 : 147 listed for HCC in Paul Brousse Hosp : 65 (75%) HIV- and 21 (24%) HIV+

28. Significant higher rate of Drop-out
on waiting-list in HIV+ patients
Drop-out : 5/21 (23%) in HIV+ vs 7/65 (10%) in HIV- , p = 0.04
Vibert et al. Hepatology 2011

29. Trend for lower survival in HIV+ but not
significant after LT for HCC
Vibert et al. Hepatology 2011

30. Similar Time to Recurrence in HIV+
Vibert et al. Hepatology 2011

31. Close follow-up of AFP and imagery
on waiting time period
AFP kinetic > 15 µg/L by month and/or AFP > 1000 µg/L : Control AFP before LT, especially in HIV+
Vibert et al. Am J Trans 2010 Duvoux et al. Gastroenterology 2012

32. 2002-2014 : Spanish Multicentric Study : 74 HIV+ and 222 HIV- transplanted for HCC
Agero et al. Hepatology 2016

33. Re Transplantation in HIV+ ?

34. No reLT in HIV+ with HCV RNA+
Aguero et al. Am J Transp 2015
42 reLT (7%) / 600 LT in HIV+14 reLT in HIV+ vs 157 reLT in HIV-
in patient wih detectable HVC RNA
Gastaca et al. Am J Transp 2012

35. HVC RNA+ was the only predictor of
mortality in 42 reLT in HIV+
Causes of reLT : Vascular Compl (35%) / PNF (22%) / Rejection (19%) / HVC Recurrence (13%)
Aguero et al. Am J Transp 2015

36. In conclusion
• HAART in HIV from 1996 had doubled the risk
of End-Stage Liver Disease and HCC
• MELD score and Sarcopenia was predictive of
survival in LT for End-Stage Liver Disease
– New HVC drugs used after LT will change the futur
• LT for HCC in HIV+ patients must be performed
after a closed follow-up of AFP before LT