HIV Positive and HIV Negative Patients Have Similar Survival Rates after Liver Transplantation, but HCV Recurrence Remains a Risk

By Liz Highleyman

With the development of effective combination antiretroviral therapy, organ transplants are no longer considered universally contraindicated for HIV positive people, but studies of transplant outcomes in this population have produced conflicting data.

Two study presented at the 44th Annual Meeting of the European Association for the Study of the Liver (EASL 2009) last month in Copenhagen add to this body of knowledge, indicating that HIV positive liver transplant recipients have survival rates similar to those of HIV negative people, but recurrence of hepatitis C virus (HCV) is a major challenge.

U.K. -- 1994-2008

In the first study, D Joshi, K. Agarwal, and colleagues from the Institute of Liver Studies at Kings College Hospital in London analyzed data from the prospective U.K. transplant database to determine long-term outcomes for HIV positive adults (age 18 or older) receiving cadaver liver transplants.

The investigators evaluated more than 6000 liver transplants performed between March 1994 and April 2008. Of these, 5435 recipients had neither HIV nor HCV, 847 (13.4%) had HCV but not HIV, and 33 (0.5%) were HIV-HCV coinfected.

HIV positive patients were younger on average than HIV negative recipients (mean 42 vs 51 years), and the coinfected group was even younger (mean 40 years). The 3 groups had comparable MELD (Model for End Stage Liver Disease) scores, a measure of liver disease severity and risk of death while awaiting a transplant.

Looking at just the HIV positive group, 29 patients (87.8%) were men, 16 (48.5%) were HIV-HCV coinfected (HCV antibody positive), 6 (18.2%) were hepatitis B virus (HBV) coinfected (HBsAg positive), and 11 (33.3%) had neither HCV nor HBV.

Results

As a group, HIV positive patients had a significantly lower average duration of survival after liver transplantation than HIV negative individuals (mean 44 vs 57 months; P = 0.0001).

The HIV-HCV coinfected group had a significantly lower mean survival duration than patients with HCV alone (29 vs 48 months; P = 0.04).

Compared with the HCV monoinfected group, survival rates were significantly lower in the HIV-HCV coinfected group (P = 0.05):

1 year: 87% vs 73%.
5 years: 69% vs 53%

However, there was no statistically significant difference in survival rates between HIV positive and HIV negative patients without HCV (P = 0.84):

1 year: 87% in both groups;
5 years: 74% vs 78%.

In a univariate analysis, HCV infection was a significant predictor of death after liver transplantation in HIV patients (odds ratio [OR] 10; P = 0.047).

In a multivariate logistic regression model including HIV-HCV coinfection, MELD score, and recipient and donor ages, the effect of coinfection was not independent of the other variables (OR 8.8; P = 0.612).

"Our data suggests that HIV positive patients have a good prognosis post-liver transplant," the investigators concluded. "Survival in [HIV-HCV coinfected] patients is significantly worse compared to [HCV monoinfected] and [HIV monoinfected] patients."

"These study results are valuable confirmation that selected HIV positive patients are as suitable candidates for liver transplant as HIV negative patients and should have similar access to treatment," said Agarwal.

The poorer post-transplant outcomes of HIV-HCV coinfected patients emphasize the need for antiviral therapy early in the course of HCV-related liver disease for this population, the researchers advised.

"We are desperate to get the newer agents, evolving agents, tested in this population at an early stage, because they have clearly an urgent need for drugs to control hepatitis C replication," co-investigator J. O'Grady told MedPage Today, referring to directly targeted "STAT-C" drugs now undergoing clinical trials in HIV negative hepatitis C patients.

Institute of Liver Studies, King's College Hospital, London, UK; Statistics and Audit Directorate, UK Transplant, Bristol, UK.

Spain -- 2001-2008

In the second study, A. Moreno and colleagues from Hospital Ramon y Cajal in Madrid, Spain, evaluated the impact of HIV coinfection on outcomes of liver transplant candidates with cirrhosis related to hepatitis B or C.

The researchers tracked the progress of all 272 patients with viral hepatitis and cirrhosis included on the liver transplant waiting list from January 2001 through October 2008. Within this group, 223 (82%) had HCV alone, 35 (13%) had HBV alone, and 14 (5%) had both HBV and HCV. A total of 37 transplant candidates (14%) had HIV. All the HIV positive patients were either HIV-HCV coinfected or HIV-HCV-HBV triple infected (none were HIV-HBV coinfected without HCV).

Results

Rates of liver transplantation, withdrawal from the waiting list, and death differed significantly between HIV positive and HIV negative transplant candidates (P = 0.001).

Transplant received: 32% vs 57%;
Withdrawal from list: 8% vs 15%;
Death 46% vs 22%.

There were no significant differences, however, when comparing patients with cirrhosis related to HBV versus HCV.

Transplant received: 57% vs 54%;
Withdrawal from list: 20% vs 14%;
Death 20% vs 26%.

The probability of survival on the waiting list was significantly lower for HIV positive compared with HIV negative transplant candidates (P = 0.0001):

90 days: 68% vs 88%;
180 days: 57% vs 77%;
365 days: 47% vs 72%.

Among candidates who did receive donor livers, there were no significant differences in survival between HIV positive and HIV negative patients:

1 year: 100% vs 85%;
3 years: 76% vs 71%;
5 years: 51% vs 65%.

Survival rates were also comparable between patients with HBV-related and HCV-related cirrhosis.

1 year: 94% vs 85%;
3 years: 83% vs 70%;
5 years: 71% vs 62%.

However, HIV positive patients were significantly more likely than those in the HCV monoinfected group to require pegylated interferon/ribavirin to treat recurrent HCV infection in their new liver (58% vs 27%; P = 0.04).

The risk of death related to HCV recurrence was also higher among HIV positive compared with HIV negative transplant recipients (100% vs 25%; P = 0.02).

Independent predictors of mortality after liver transplantation were older age when added to the waiting list, higher MELD score at the time of transplant, and cytomegalovirus (CMV) disease after transplantation.

Based on these findings, the investigators concluded, "HIV [positive] subjects had a significantly poorer survival on waiting list."

"The probability of survival after liver transplantation was similar in HIV [positive] subjects, but they more frequently needed [pegylated interferon/ribavirin] and 100% of deaths were related to HCV recurrence," they added.

These findings also underscore the importance of treating hepatitis C and hopefully achieving sustained response before liver transplantation -- or better yet, before liver disease progresses to the stage at which a transplant becomes necessary.

Infectious Diseases, Liver-Gastroenterology (Liver Transplant Unit), Clinical Biostatistics Unit, Transplant Coordination Unit, Pathology (Liver Section), Microbiology (Virology), Hospital Ramon y Cajal, Madrid, Spain.

5/05/09

References

D Joshi, V Aluvihare, A Belgaumkar, and others. UK liver transplant experience of HIV: long term outcomes. 44th Annual Meeting of the European Association for the Study of the Liver (EASL 2009). Copenhagen, Denmark. April 22-26, 2009.

A Moreno, R Bárcena, S del Campo, and others. Quereda1, Impact of HIV-coinfection on the outcome of viral cirrhosis liver transplant candidates at a reference center from 2001-2008 and predictors of post-transplant survival. EASL 2009. Copenhagen, Denmark. April 22-26, 2009.

Other source

M Smith. HIV No Barrier to Liver Transplant. MedPage Today. April 24, 2009.

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15th Conference on Retroviruses and Opportunistic Infections (CROI 2009)
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