Liver Transplantation for HIV/HCV Coinfection

Where Is the Controversy?

Emily Dannhorn; James P O'Beirne

Disclosures

Future Virology. 2013;8(7):639-648. 

In This Article

LT for HIV/HCV Coinfection: A Work in Progress?

Although not necessarily demonstrating improved results, more recent multicenter reports have been able to identify a number of patients who could potentially make up a subgroup of HIV/HCV-coinfected individuals with improved graft survival and mortality rates after LT. Miro et al. carried out a prospective multicenter cohort trial examining the outcomes of 84 HIV/HCV-coinfected patients and 252 matched HCV-monoinfected patients undergoing LT between 2002 and 2006.[32] The majority of patients were HCV genotype 1. They demonstrated that LT was an effective short-term procedure in both mono- and co-infected patients, with similar 1-year survival rates (88 vs 90%). However, following longer periods of time, survival in the coinfected group was significantly lower (5-year survival: 54 vs 71%; p = 0.008). HIV was identified as an independent predictor of death in patients with HCV.

Other than survival, there were additional important differences between the two groups. For instance, biopsy-proven acute cellular rejection was much more common in the coinfected group (38 vs 20%; p < 0.001). The cause of this is speculative, but presumably HIV-linked immunomodulation and problems achieving satisfactory immunosuppressive levels due to drug interactions are operative. The increased rates of rejection and its subsequent treatment observed in the coinfected group could be responsible for more severe HCV recurrence, as is seen in studies of monoinfection and LT.[33,34] In multivariate analysis, other factors relevant to mortality in the coinfected group were MELD score pretransplantation, LT performed at a center with low activity (at centers performing <1 transplant/year, mortality was almost three-times higher) and infection with HCV genotype 1. Having a negative HCV RNA viral load at any time (pre- or post-LT) had a positive impact on mortality. As previously established, factors pertaining to the donor (e.g., donor risk index) also correlated with survival.

A similar study published by Terrault et al. allows further analysis of factors associated with poor outcome.[35] This study was prospective and collected data from multiple centers in the USA, comparing patient and graft survival for 89 HIV/HCV-coinfected patients and two control groups: 235 patients with HCV monoinfection and all US transplant recipients over the age of 65 years between 2003 and 2010.[35] Eight of the coinfected cohort underwent combined liver–kidney transplantation. Patients in the study underwent transplantation at 17 different centers across the USA.

The results demonstrated that HIV/HCV patients were younger at transplant than their HCV controls, and had a lower BMI at listing. They were also more frequently coinfected with HBV. Coinfected recipients also received a higher proportion of organs from donation after circulatory death (DCD) donors, and had longer warm ischemic times – factors known to be related to an increased risk of graft loss.[36] Immunosuppressive regimens in the coinfected group were less likely to involve tacrolimus-based agents in the initial stages. The 1- and 3-year survival rates were 76 and 60% for HIV/HCV-coinfected patients, and 92 and 79% for HCV-monoinfected patients (p < 0.001). Graft loss due to infection or multiorgan failure was observed more frequently in the coinfected group; graft loss due to malignancy was seen more in the monoinfected cohort. Of note, there were no deaths due to infections related to HIV, and a history of AIDS-related pathology pretransplant was not associated with worsened survival post-transplantation.

In the multivariate analysis, HIV was the only factor associated with a significantly increased risk of death. In the coinfected group, undergoing combined liver–kidney transplantation was associated with increased mortality. As with the results from Miro et al.,[32] a lower BMI (BMI <21 at listing) was a predictor of increased mortality, as was receiving an organ from an non-HCV-positive donor, or an older age donor. When coinfected patients without these 'high-risk factors' were analyzed, the outcomes in terms of postoperative graft and patient survival were similar to those in the >65 years of age control group.

Increased rates of rejection were also demonstrated in the coinfected group compared with the HCV-monoinfected group in this study. The incidence of rejection over a 3-year period was 39% in the coinfected group versus 24% in the HCV-monoinfected patients; in excess of 50% of episodes occurred within the first 21 days post-LT in the HIV/HCV group. HIV was the only factor significantly associated with rejection.

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