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 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

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

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

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)

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 US2003 – 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

Subramanian et al. Gastroenterology 2010

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

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%

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

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

Result of LT in End Stage Liver

disease in HIV patient ?

Author

Journal Year nSurvival (%)

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

13100

Author

Journal Year nSurvival (%)

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

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

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

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

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, FCHW: week; SVR: sustained virological response

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

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 35 HIV/HCV cirrhotic patients with HCC

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 hypertension

Not candidate for LT

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+

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

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 AFP before LT, especially in HIV+

Vibert et al. Am J Trans 2010 Duvoux et al. Gastroenterology 2012

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 HIV-

in patient wih detectable HVC RNA

Gastaca et al. Am J Transp 2012

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

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