Outcomes
of Liver Transplantation in HIV Positive Recipients Coinfected with Hepatitis
B or C By
Liz Highleyman
 Traditionally,
HIV positive individuals were considered
poor candidates for organ transplantation this consensus began to change after
the advent of effective combination antiretroviral
therapy. Today, many experts believe patients with well-controlled HIV and
well-preserved immune function are appropriate transplant candidates.
To
date, some studies have found that HIV positive liver transplant recipients have
similar outcomes to those of HIV negative patients, while others have shown that
people with HIV have worse outcomes. Three posters presentations at the 16th
Conference on Retroviruses and Opportunistic Infections (CROI 2009) last month
in Montreal shed further light on this issue.
5
Year Survival in Spain
In
the first study, Jose Miro and colleagues from multiple centers in Spain looked
at 5-year survival rates in HIV positive liver transplant patients with hepatitis
C virus (HCV) coinfection.
Recurrent HCV after liver transplantation is
a major cause of graft (donor liver) loss and death, they noted as background.
Prior studies performed in single centers with smaller numbers of patients suggest
poorer survival in HIV-HCV coinfected patients compared with HCV monoinfected
individuals.
This case-control study included 81 consecutive HIV-HCV coinfected
patients who underwent orthotopic liver transplantation between 2002 and 2006,
and were followed through December 2007.
HIV positive liver recipients
were matched (1:3 ratio) with 243 HCV monoinfected patients who had undergone
liver transplantation during the same period at the same institutions. Case (HIV
positive) and control (HIV negative) participants were matched for sex, age (+/-
12 years), calendar year, center, presence of hepatitis
B virus (HBV), and presence of hepatocellular
carcinoma (HCC). The median age was 42 for coinfected and 46 for HCV
monoinfected patients. In both groups, 78% were men, 16% had HBV, and 8% had
HCC.
During a median 2.6 years of follow-up, 29 (35.8%) HIV-HCV coinfected
patients and 51 (20.9%) HCV monoinfected patients died. In both groups, 5.0% required
a repeat transplant. Survival rates for coinfected and HCV monoinfected liver
recipients were at 87.5% vs 89.1% at 1 year, 70.8% vs 75.9% at 2 years, 61.8%
vs 77.4% at 3 years, 58.3% vs 76.2% at 4 years, and 47.9% vs 75.1% at 5 years.
A similar pattern was seen for graft survival, with the disparity between HIV-HCV
coinfected and HCV monoinfected patients increasing over time.
"Short-term
patient and graft survival in [HIV-HCV] orthotopic liver transplant coinfected
patients was similar to that of HCV monoinfected orthotopic liver transplant recipients,"
the investigators concluded. "However, mid- to long-term survival was poorer
in [HIV-HCV] coinfected patients."
Outcomes
in French Patients
In
the second study, Elina Teicher and colleagues from France evaluated clinical,
biological, and immuno-virological outcomes in a cohort of 88 consecutive HIV-HCV
or HIV-HBV coinfected patients who received a liver graft at a single center between
December 1999 and September 2008. All
transplants recipients had well-controlled HIV infection with a CD4 count greater
than 100 cells/mm3, undetectable plasma HIV viral load on antiretroviral therapy
at the time of waiting list enrollment, and no previous opportunistic
infections (OIs). Most
participants (50%) were men and the mean age was 44 years. Indications for liver
transplantation were HCV-related
liver cirrhosis (n=68), HBV-related cirrhosis (n=14), regenerative nodular
hyperplasia (n=3), fulminant hepatitis (n=2), and hemochromatosis (n=1). Antiretroviral
therapy (ART) was discontinued during surgery and the immediate post-operative
period. Post-transplant ART typically consisted of 2 nucleoside/nucleotide reverse
transcriptase inhibitors (NRTIs) plus a protease inhibitor (58%) or a NNRTI (14%);
19% took enfuvirtide (T-20; Fuzeon).
All patients also received OI prophylaxis. Primary immunosuppressive therapy to
prevent organ rejection included tacrolimus or cyclosporine, mycophenolate mofetil,
and prednisone.
After transplantation, 3 patients experienced an increase
in HIV viral load. The average CD4 count fell from 286 cells/mm3 pre-transplant
to 222 cells/mm3 at 6 months post-transplant, but then rose to 250 cells/mm3 by
12 months. Survival rates were 78% at 2 years and 73% at 5 years. Five opportunistic
infections were diagnosed (2 esophageal candidiasis, 2 CMV, 1 lymphatic tuberculosis).
Ten patients (11%) died due to a severe recurrence of HCV infection (n=10), while
4 died due to recurrent HCC. About one-third developed kidney failure. About
one-third of patients (n = 23) received interferon-based
anti-HCV therapy due to severe hepatitis or accelerated liver
fibrosis. Three individuals who were successfully treated before transplantation
continued to have undetectable HCV RNA for more than 2 years, with normal liver
histology. Seven patients developed stage F3 (severe) fibrosis, 2 developed cirrhosis,
and 3 developed early HCC recurrence. "Liver
transplantation performed in HIV-infected patients with controlled HIV infection
is feasible providing strict selection criteria are respected in well disciplined
patients with multi-disciplinary care management," the researchers concluded.
"No deleterious impact on CD4 T-cell counts was observed; immunosuppressive
therapy does not alter the immune responses against OI," they added. "However
the severe recurrence of HCV infection after liver transplantation remains a major
issue in HIV-HCV [co]infected patients."
Outcomes
in Patients with Cirrhosis
Finally,
another Spanish team looked at outcomes among HIV positive liver transplant recipients
with HBV-related or HCV-related cirrhosis.
Ana Moreno and colleagues conducted
a retrospective-prospective, non-randomized study of all 245 patients at their
center with cirrhosis secondary to viral hepatitis on the liver transplant waiting
list between July 2001 and July 2008.
Of the 245 patients on the list,
35 (14%) were HIV positive. Among these, 86% had HIV-HCV coinfection while 14%
had HIV-HCV-HBV triple infection (none of the HIV positive participants had HBV
without HCV). Again, most were men and the HIV positive patients were older than
HIV negative individuals (41 vs 53 years). More than twice as many HIV positive
patients had received interferon-based therapy (21% vs 56%).
During follow-up,
38% of coinfected patients received a transplants compared with 61% of HIV negative
patients; 9% and 17%, respectively, withdrew from the waiting list. HIV positive
recipients were more than twice as likely to die as those without HIV (53% vs
23%). The probability of survival on the waiting list was significantly lower
for HIV positive patients at 3 months (67% vs 85%), 6 months (48% vs 72%), and
12 months (40% vs 64%).
Independent predictors of mortality were a higher
MELD score and prior or current ascites. After adjusting for MELD score, HIV coinfection
had a negative effect on survival, but this did not reach statistical significance
(hazard ratio 1.56; P = 0.109). HIV positive and HIV negative patients spent a
similar amount of time on the waiting list (median 217 vs 247 days).
Among
patients who did receive transplants, in contrast to the Spanish study described
above, here the probability of survival was similar in HIV positive and HIV negative
people at 1 year (100% vs 71%), 2 years (75% vs 60%), 3 years (75% vs 57%), and
5 years (50% vs 53%), with the disparity narrowing rather than widening over time.
However, HIV positive patients were more likely to die due to HCV recurrence.
HIV
positive patients with cirrhosis related to HCV or HCV-HBV on the liver transplant
waiting list had "significantly higher mortality than non-HIV subjects,"
the researchers concluded. "Survival after liver transplantation was similar
in both groups, but HIV subjects more frequently needed pegylated interferon/ribavirin
and died due to HCV recurrence.
3/24/09 References J
Miro, M Montejo, L Castells, and others. 5-Year Survival of HCV/HIV-co-infected
Liver Transplant Recipients: A Case/Control Study. 16th Conference on Retroviruses
and Opportunistic Infections (CROI 2009). Montreal, Canada. February 8-11, 2009.
Abstract 833. E
Teicher, J-C Duclos Vallée, D Samuel, and others. Liver Transplantation
in 88 HIV-infected Patients. CROI 2009. Abstract 834.
A Moreno, R Bárcena,
S Del Campo, and others. Effect of HIV Co-infection on the Outcome of Viral Cirrhosis
Liver Transplant Candidates on the Waiting List at a Reference Center from 2001
to 2008. CROI 2009. Abstract 835 |
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