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 HIV and Coverage of the
16th Conference on Retroviruses and
Opportunistic Infections (CROI 2009)

 February 8 - 11, 2009, Montreal, Canada

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.



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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