Liver transplantation for an HIV-positive patient in the era of highly active antiretroviral therapy

In the 1980s, before the availability of HIV screening tests, several transplant recipients acquired HIV from contaminated organs or blood products ^[1,2]. Many of these patients died prematurely as a consequence of opportunistic infection. At this time it was observed that the survival rate of HIV-positive was inferior to that of HIV-negative transplant recipients ^[1]. Many units thus considered HIV infection to be a contraindication to organ transplantation, an attitude that still persists in many transplant centres now. A 1997 survey ^[3] of renal transplant units examined attitudes to HIV-positive patients. Eighty-four per cent said that they would not transplant an individual who was HIV positive. Among the few centres who said they would consider transplanting an HIV-positive recipient, none had performed such a transplant.

HIV infection and chronic liver disease often co-exist as a result of the shared routes of acquisition of HIV and hepatitis B and C. Before the development of effective antiviral therapy many co-infected patients died of AIDS before they had progressed to overt liver failure. With the development of effective highly active antiretroviral therapy, patients with HIV are now living much longer. Therefore, increasing numbers of patients with stable HIV infection are progressing to end-stage liver failure. Nevertheless, attitudes to the transplantation of HIV-infected patients have been slow to adjust, and many transplant centres still regard HIV infection as a contraindication to transplantation.

We report the case of a 42-year-old man who suffered from severe haemophilia A. He was HIV positive and was transplanted in July 1999 for advanced hepatitis C cirrhosis complicated by a small hepatocellular carcinoma. Pre-transplant antiviral therapy entailed saquinavir, stavudine and lamuvidine. Pre-transplant HIV RNA was not detectable (Chiron Multiplex version 3 assay; limit of detection 50 copies/ml). The CD4 lymphocyte count pre-transplant was 287 cells/μl.

Liver transplantation was an uncomplicated procedure. The postoperative course was complicated by chest infection, sputum retention and respiratory failure, necessitating a 20 day stay in intensive care. Opportunistic pathogens were not isolated. Antiretroviral therapy was withheld for the first 14 postoperative days, thus minimizing the potential for drug interactions and drug toxicity (secondary to liver or renal dysfunction).

The patient received standard triple immunosuppression with azathioprine, cyclosporine and corticosteroids. Post-transplant antiretroviral therapy included abacavir, stavudine and lamivudine. The substitution of abacavir for saquinavir avoids the predictable impact of cytochrome P450 inhibition on cyclosporine metabolism ^[4,5]. At 3 months post-transplant abacavir was stopped because of possible gastrointestinal side-effects, and saquinavir was reintroduced. At 9 months post-transplant saquinavir was replaced with nevirapine (because of the patient's concern about the association of the former drug with lipodystrophy). At 11 months post-transplant the patient developed acute appendicitis and an uncomplicated appendectomy was performed. During the first post-transplant year there has been persistent but asymptomatic biochemical liver dysfunction. Liver biopsy 12 months after transplantation revealed normal architecture with mild chronic hepatitis. The patient remains well. Current antiretroviral treatment consists of lamivudine, stavudine and nevirapine, and current immunosuppression is tacrolimus 1 mg a day. HIV titres and CD4 cell counts during the 12 month period are summarized in Table 1.

Table 1

Currently, there is little published experience of liver transplantation for HIV-infected patients. This case demonstrates that a good short-term outcome can be expected. Drug interactions and the side-effects of antiviral therapy complicate post-transplant care. In the context of transplantation for the HIV/hepatitis C co-infected patient, recurrent hepatitis virus infection of the transplanted liver may pose the greatest challenge. For hepatitis C infection, graft reinfection is probably inevitable. Although some units have used interferon and ribavirin to treat or prevent recurrent hepatitis, the use of these antiviral agents in addition to immunosuppressive medication and antiretroviral drugs adds yet another dimension of potential drug interactions to an already challenging cocktail.

Attitudes to organ transplantation in HIV-positive patients need to be reconsidered. Limited published data describing the long-term outcome and recent major developments in the treatment of HIV infection demand a revision of policies that excluded these patients from organ transplantation.

Paul J. Gow

David Mutimer