What Is the Impact of HIV Infection on Survival After Liver Transplantation?

Nyingi Kemmer; Kenneth E Sherman

Nat Clin Pract Gastroenterol Hepatol.  2008;5(8):426-427.  ©2008 Nature Publishing Group

Posted 08/13/2008

Synopsis

Background

HIV infection has not been considered a contraindication to orthotopic liver transplantation (OLT) since highly active antiretroviral therapy (HAART) became available in 1997; however, many OLT centers still exclude patients with HIV infection from OLT because of reported poor outcomes.

Objective

To determine the influence of HIV infection on patient survival after OLT.

Design and Intervention

This US, retrospective study examined data from the United Network for Organ Sharing (UNOS) database. Patients aged ≥ 18 years who had undergone liver transplantation, or multiple organ transplantation including the liver, between January 1997 and October 2006 were identified for inclusion in the study. Exclusion criteria included patients without data on vital or HIV status at the end of follow-up. Data of eligible patients were extracted from the database for analysis, which included the evaluation of 19 pre-OLT recipient variables (including age, co-infection [with HCV or HBV] and model for end-stage liver disease (MELD) score) and 7 donor variables. Univariate and multivariate analyses were performed to determine any associations between variables and outcomes.

Outcome Measure

The main outcome measure was post-OLT survival.

Results

A total 138 OLT recipients with HIV infection and 30,520 OLT recipients without HIV infection were included in the study. Total follow-up duration for OLT recipients with and without HIV was 150.55 and 89,845.82 person-years, respectively. OLT recipients infected with HIV had significantly lower survival rates than recipients without HIV infection: estimated 2-year and 3-year survival was 70% versus 81% and 66% versus 77%, respectively (P = 0.04); however, these differences seemed entirely attributable to the group of OLT recipients with co-infection (HIV plus HCV or HBV co-infection), as no deaths occurred during follow-up in recipients with HIV infection only. OLT recipients co-infected with HIV and HCV had a significantly lower survival rate than OLT recipients infected with HCV only (P = 0.006). In addition, death rates were significantly higher in OLT recipients with HIV and HCV co-infection than recipients with HIV infection only (P = 0.003). Recipients with HBV and HIV co-infection had a higher rate of death than recipients with HIV infection only, but this finding was not significant. Regression analysis revealed that OLT recipients with HIV had a hazard ratio for death of 1.41 (P = 0.14; 95% CI 0.90–2.22).

Conclusion

Individuals with HIV infection have good outcomes after OLT; however, individuals with HIV and HCV co-infection have poor outcomes after OLT that are significantly poorer than those of individuals infected with HCV or HIV only.

Commentary

The survival of HIV-infected individuals has improved markedly since the introduction of HAART. An untoward result of the success of this therapy has been the emergence of end-stage liver disease as a significant cause of morbidity and mortality in patients with HIV infection.[1] As a consequence, an increasing number of HIV-infected patients are in need of OLT. Reports of poor OLT outcomes among HIV-infected individuals in the pre-HAART era led to reduced enthusiasm for OLT as a therapeutic option for these patients.[2] However, in the past decade, with the advent of novel immunosuppressive agents and advances in surgical techniques, post-transplant outcome has improved in all recipients irrespective of HIV status. The use of OLT for HIV-infected individuals has evolved from being absolutely contraindicated to being a viable option in selected patients on a stable HAART regimen with undetectable plasma HIV RNA and a CD4 count >100 cells/mm3.[3]

As reports of experiences with HIV-positive OLT recipients emerge, our approach to their immunosuppressive management–which requires attention to such complexities as unique drug–drug interactions, the increased risk of infection and a need for multidisciplinary transplant teams–continues to improve. The unique challenges of the altered pharmacokinetic profiles of calcineurin inhibitors (e.g. ciclosporin and tacrolimus) and mTOR inhibitors (e.g. sirolimus) as a result of drug–drug interactions, and the known HAART-related inhibition or induction of cytochrome P450 enzymes, have prompted aggressive therapeutic drug monitoring and dose modifications that are specific to this population.[2]

The study by Mindikoglu et al. provides an update of the outcome of OLT among HIV-infected recipients in the HAART era. The authors report lower survival rates in recipients with HIV infection than recipients without HIV infection, but analysis reveals that this finding is attributable to patients with HIV and HCV coinfection. There are multiple reports that document that the severity and rate of HCV recurrence in recipients with HIV and HCV coinfection is much higher than in recipients with HCV infection only, and is invariably associated with increased mortality.[1,4] Following OLT in patients with HCV and HIV co-infection, issues of drug intolerance and poor efficacy complicate use of interferon-based therapies.[2] It is, therefore, clear that new treatment strategies are needed to improve outcomes in HCV-infected OLT recipients with or without HIV infection. The development of small molecules specifically targeted against HCV is progressing at a rapid pace, but the use of these agents in OLT recipients with HCV and HIV co-infection might be limited by drug interactions with both antiretroviral agents and immunosuppressive drugs.

The report by Mindikoglu et al., although lacking vital information on HIV viral load and CD4 count at the time of OLT, is encouraging. However, the retrospective nature of the design does not permit the complete assessment of contributory factors to outcomes. An NIH-sponsored, multicenter, prospective trial addresses many of these issues. Interim data from this trial provides further support for use of OLT in HIV-infected patients.[5] No evidence of HBV recurrence has been reported in OLT recipients with HBV and HIV co-infection. HIV control has been maintained even in the presence of appropriate immunosuppression following organ transplantation.

Practice Point

Health-care providers must recognize the signs and symptoms of end-stage liver disease in patients with HIV infection and appropriately refer these patients for potential liver transplantation at centers with expertise in treating this population

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References

1.        Pineda JA and Garcia-Garcia JA et al. (2007) Clinical progression of hepatitis C virus-related chronic liver disease in human immunodeficiency virus-infected patients undergoing highly active antiretroviral therapy. Hepatology 46: 622–630

2.        Samuel D et al. (2008) Are HIV-infected patients candidates for liver transplantation? J Hepatol 48: 697–707

3.        Stock PG and Roland ME (2007) Evolving clinical strategies for transplantation in the HIV-positive recipient. Transplantation 84: 563–571

4.        Duclos-Vallee JC et al. (2008) Survival and recurrence of hepatitis C after liver transplantation in patients coinfected with human immunodeficiency virus and hepatitis C virus. Hepatology 47: 407–417

5.        Roland ME et al. (2008) HIV-infected liver and kidney transplant recipients: 1- and 3-year outcomes. Am J Transplant 8: 355–365

Acknowledgements

The synopsis was written by Rachel Jones, Associate Editor, Nature Clinical Practice.