Uzma Sarwar MD
Coincident with greater use of highly active antiretroviral therapy (HAART), chronic liver disease has become one of the leading causes of death amongst HIV patients. This reflects the high prevalence of chronic liver diseases in the HIV-infected; almost a third of HIV-seropositive patients are afflicted with liver disease, predominantly as a result of hepatitis B and/or hepatitis C co-infection. Given their increased life-span, many HIV-infected patients now progress to end-stage liver disease, where they used to succumb to the effects of HIV prior to death due to liver disease, in the pre-HAART era. Liver transplantation is commonly considered for treatment of end-stage liver disease among the HIV seronegative population, but the situation is not as clear-cut for patients infected with HIV.
In the past, HIV was considered an absolute contraindication to liver transplant due to the infecteds’ overall poor prognosis and their inability to continue immunosuppressive therapy post transplant. The winds have now shifted and liver transplantation is now considered possible in this population. However, only 26 centers in the United States consider HIV-positive patients for liver transplant. Preliminary reports on the safety and efficacy of transplant in HIV positive patients are encouraging, having revealed that carefully selecting HIV-infected patients to receive solid organ transplants results in low rejection rates, few opportunistic infections and survival rates comparable to non HIV-seropositive patients. An outcome study of nineteen HIV patients conducted in 2002 by Roland, et al. at UCSF is particularly salient. In this study, transplanted patients, whose baseline CD4 cell count was 280 and whose plasma viral load was between undetectable and 115,000, experienced a low graft rejection rate of 21% after 300 days post-transplant. Another retrospective analysis of 15 HIV-infected patients (baseline CD4 cell count >100 and plasma viral load between undetectable and 141,000) who underwent transplant from 1999 to 2006 at the University of Miami, showed similar survival rates when compared with 857 HIV-uninfected patients, after 38 months median follow-up. However the HIV patients did have a higher rate of infectious complications.It should be noted that these studies did not specifically examine patients who underwent liver transplantation, but all HIV patients receiving solid organ transplants. Therefore, it is necessary for studies to specifically examine outcomes of liver transplantation in the HIV-infected population. Further, studies comparing long-term survival between transplanted HIV-infected and uninfected patients have yet to be reported.
In addition to the traditional criteria used for transplant eligibility, HIV patients have stricter inclusion criteria for consideration and enrollment. Some of the prominent criteria that have been utilized in previous studies are included below.
Inclusion Criteria:
Life expectancy greater than 5 years
CD4 cell count greater than 200 for over 6 months pre-transplant
Adherence to stable HAART regimen
Absence of any AIDS defining illness
Plasma viral load less than 50 copies/ml
Exclusion Criteria:
Presence of any cancer diagnosis
Any untreated chronic illness (included tuberculosis)
Greater than 3 classes of viral resistance
Persistent HIV viremia
Any non-compliance with HAART
To conclude, with careful and stringent selection criteria, HIV-infected patients may be considered for liver transplantation. They appear to have similar short-term survival post-transplant as do HIV-uninfected patients, although more studies are needed to evaluate their long-term prognosis.
Dr. Sarwar is a third year internal medicine resident at NYU Medical Center.
Reviewed by Michael Poles MD, Associate Editor, Clinical Correlations, Assistant Professor of Medicine, NYU Division of Gastroenterology
References
1. Kozei, margaretJ, Peters, Marion G, Viral Hepatitis in HIV infection, NEJM 2007; 356:1445-54
2. Sulkowski MS et al, Rapid fibrosis progression among HIV/Hep C virus co-infected adults, AIDS 2007;16:2209-16
3. Merchante N et al, Survival and prognostic factors of HIV infected patients with HCV related end stage liver disease, AIDS 2006;20:49-57
4. Hadler, SC, Judson, FN, O’Malley PM et al, Outcome of hepatitis B virus infection in homosexual men and its relation to prior HIV infection
5. Thio et al, HIV-1, HBV and risk of liver related mortality in the Multicenter Cohort study. Lancet 2002;360:1921-6
6. Roland et al, Solid organ transplantation in HIV infected patients in potent anti-retroviral therapy era. Topics in HIV medicine;12:73-6
7. Schreibman Ian et al, Outcomes after orthotropic liver transplantation in fifteen HIV infected patients. Transplantation 2007; 84:697-704
8. Powderly, William, Antiretroviral therapy in patients with hepatitis and HIV: weighing the risks and benefits, CID 2004;38:109-113
9. Vennarecci,G et al, Transplantation in HIV positive patients. Transplantation Proceedings 2007;39:1936-38
10. Sanchez-Conde M, Berenguer, J, Miralles, P et al, Liver biopsy findings for HIV infected patients with chronic hepatitis C and persistently normal levels of alanine aminotransferases, Clin Infect Dis 2006; 43:640-4
11. Uptodate.com
12. Harrison’s Manual of Internal Medicine, 16th edition