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Liver Transplantation in the setting
of HIV infection
Eric Vibert, MD, PhD
Hopital Paul Brousse, AP/HP
Villejuif, France
Summary
• Epidemiology of liver disease in HIV+ patient
• Why liver transplantation is feasible HIV+ patient ?
• Result of...
Epidemiology of liver disease in
HIV patient
1996 : Highly Active Anti-Retroviral
Therapy (HAART) in HIV patients
Giordano et al. Arch Int Med 2008
HIV/HCV
HIV
HIV/HCV...
Rate of ELD and HCC in HIV/HVC
Ioannou et al. Hepatology 2013
6% of End-Stage Liver Disease 1.6% of Hepatocellular carcino...
Why LT is feasible in HIV ?
Survival is dependent of MELD Score and not HIV status
1999 to 2005 : 35 HIV/HVC coinfected patients transplanted
2008
Similar mortality on waiting list in HIV
patients listed without HCC in US
2003 – 2007 : 20 transplant centers in US : 167...
Subramanian et al. Gastroenterology 2010
Indication of LT in 132 HIV+ Patients
in Paul Brousse Hospital, France
Indication of Liver Transplantation N (%)
HVC Cirrh...
No impact of Infection on Survival in
109 HIV+ transplanted patients
4/109 (3.6%) developed opportunistic infection with a...
Cause of 43 deaths after LT
1-year patient mortality : 7%
3-year patient mortality : 33%
5-year patient mortality : 39%
Te...
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...
Result of LT in End Stage Liver
disease in HIV patient ?
Author
Journal Year n
Survival (%)
1yr 3 yrs
Fung et al.
Liver Transplant 2004
3 100
-
Norris et al.
Liver Transplant 2004...
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...
Higher rate and more severe
recurrence of HVC after LT in HIV
Progression to Fibrosis after LT for
HVC with or without HIV...
Sofosbuvir-based regimens in 16 HIV/HCV
co-infected patients after liver transplantation:
ANRS CO23 CUPILT study
TM Antoni...
HCV virological response
13%
40%
73%
81%
100% 100%
94% 94%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100% *
*virological rela...
Castells et al. J Hepatol 2015
78 HIV/HCV coinfected patients treated before New HVC treatment
New HVC treatment will dras...
Results of LT for HCC in HIV patient
1992 to 2006 : 63 patients in 6 centers
Survival are similar and treatment is usefull
2007
Higher Rate of Infiltrative HCC in HIV
Lewin et al. Radiology 2015
2008 – 2012 : French multicentric prospective study of ...
Lewin et al. Radiology 2015
Correlation with low CD4 rate and
infiltrative HCC tumor
Lewin et al. Radiology 2015
CD4 < 200 cell/µL without portal hype...
Intent-to-treat result analysis : 21 listed then 16 HIV transplanted for HCC
LT for HCC in HIV+ patient
Vibert et al. Hepa...
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- ,...
Trend for lower survival in HIV+ but not
significant after LT for HCC
Vibert et al. Hepatology 2011
Similar Time to Recurrence in HIV+
Vibert et al. Hepatology 2011
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 ...
2002-2014 : Spanish Multicentric Study : 74 HIV+ and 222 HIV- transplanted for HCC
Agero et al. Hepatology 2016
Re Transplantation in HIV+ ?
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 H...
HVC RNA+ was the only predictor of
mortality in 42 reLT in HIV+
Causes of reLT : Vascular Compl (35%) / PNF (22%) / Reject...
In conclusion
• HAART in HIV from 1996 had doubled the risk
of End-Stage Liver Disease and HCC
• MELD score and Sarcopenia...
Liver Transplantation in the setting of HIV infection
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Liver Transplantation in the setting of HIV infection

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

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Liver Transplantation in the setting of HIV infection

  1. 1. Liver Transplantation in the setting of HIV infection Eric Vibert, MD, PhD Hopital Paul Brousse, AP/HP Villejuif, France
  2. 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. 3. Epidemiology of liver disease in HIV patient
  4. 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. 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. 6. Why LT is feasible in HIV ?
  7. 7. Survival is dependent of MELD Score and not HIV status 1999 to 2005 : 35 HIV/HVC coinfected patients transplanted 2008
  8. 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. 9. Subramanian et al. Gastroenterology 2010
  10. 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. 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. 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. 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. 14. Result of LT in End Stage Liver disease in HIV patient ?
  15. 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. 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. 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
  18. 18. 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
  19. 19. 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
  20. 20. 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
  21. 21. Results of LT for HCC in HIV patient
  22. 22. 1992 to 2006 : 63 patients in 6 centers Survival are similar and treatment is usefull 2007
  23. 23. 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
  24. 24. Lewin et al. Radiology 2015
  25. 25. 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
  26. 26. 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+
  27. 27. 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
  28. 28. Trend for lower survival in HIV+ but not significant after LT for HCC Vibert et al. Hepatology 2011
  29. 29. Similar Time to Recurrence in HIV+ Vibert et al. Hepatology 2011
  30. 30. 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
  31. 31. 2002-2014 : Spanish Multicentric Study : 74 HIV+ and 222 HIV- transplanted for HCC Agero et al. Hepatology 2016
  32. 32. Re Transplantation in HIV+ ?
  33. 33. 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
  34. 34. 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
  35. 35. 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

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