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Liver Transplants in HCV/HIV Coinfection?
Dear Dr. Chung
My name is C. and I'm from Red Deer, Alberta, Canada and I was wondering if I could get some information from you. I'm co-infected with HIV/HCV and need a Liver Transplant. They have never done one with co-infection before in Canada and it sounds quite scarry. They say that I'm a candidate for a transplant but I would like some more information before I make a decision.
Do you know of anyone that has gone through this ordeal that I might talk to?
Dr. Chung writes--
I would advise that you contact one of the several American centers exploring liver transplant in HIV/HCV. These include UCSF, Mt. Sinai, and Pittsburgh, to name several. They will have recipients you may be referred to. RC
Answer from Jules Levin:
A small number of liver transplants have been done in HCV/HIV infected patients at UCSF, the University of Pittsburgh and in Europe in UK and France, some with success for a limited follow-up and some without success. Most recently I was told about 3 transplants in France in HCV/HIV coinfected persons and I was told all 3 are doing ok with limited follow-up, the longest is 25 months I think. A national liver transplant program in HIV is trying to be established at 12 US hospital sites around the country to establish if the transplants can be done but this is merely a pilot program.
A main goal is to attain reimbursement which is an obstacle because it is expensive. The advent of pegylated interferon is an important advance in that treatment response for HCV and for treating HCV if it reoccurs after transplantation. Often afyer the transplant HCV reoccurs and improved treatment with pegylated interferon should help survival. It's possible that the University of Pittsburgh has the best developed program as of now in the US. The University of Pittsburgh Protocol (this report was written in the Summer of 2000 for <www.medscape.org> and I don't have an update since then).
The University of Pittsburgh developed a protocol to carefully assess the impact of HIV infection and transplantation on patients with end-stage organ failure. Inclusion criteria included minimal transplant listing criteria. Additionally, patients must have demonstrated a clinical response to antiretroviral therapy as an indication of the ability to control the disease postoperatively. Exclusion criteria included active opportunistic infection, Kaposi's sarcoma, and inability to follow a complex medication schedule after transplant. A diagnosis of AIDS was deliberately left out as an exclusion criterion. The current definition of AIDS includes the presence of 1 of 25 conditions, or a CD4 T-cell count below 200. However, a number of these conditions can be seen in patients with end-stage organ disease without AIDS, necessitating a careful review of each patient to determine the impact of organ failure (especially liver failure) on these processes.
Clinical responsiveness to antiretroviral therapy is defined as a CD4 T-cell count greater than 200 for 6 months and an undetectable viral load for 3 months. Exceptions are made for patients with liver failure, since portal hypertension and splenic sequestration may artificially lower cell counts. Thus, the lower limit for cell counts for patients with liver failure is set at 100. Additionally, many patients cannot tolerate HAART due to its hepatotoxic effects. In such cases, having a viral load is acceptable if it can be predicted that HAART will be effective postoperatively when normal liver function returns.
Under the University of Pittsburgh protocol, 5 patients underwent liver transplantation and 3 underwent kidney transplantation in the HAART era. All patients were on HAART therapy prior to transplant except for 1 kidney recipient who had nonprogressive HIV disease. The patients with liver failure were managed with regimens including 2 NRTIs and 1 PI, whereas the patients with renal failure received 2 NRTIs and 1 NNRTI. All patients received TAC and corticosteroid-based immunosuppression, with selective use of MMF and rapamycin.
The 3 renal transplants were transplanted for presumed hypertensive-related nephropathy, although in retrospect, 2 of these patients may have had HIVAN. One patient developed chronic rejection and lost the allograft 8 years posttransplant. A second patient developed moderate rejection reversed by corticosteroids; this patient's baseline serum creatinine is now 2.8-3.0 mg/dL. The third patient experienced 1 episode of mild rejection and maintains a serum creatinine of 1.4-1.6 mg/dL. One patient developed asymptomatic cytomegalovirus (CMV) infection requiring treatment with DHPG (later approved as acyclovir). All patients are alive at follow-ups of 1, 2, and 11 years. Viral load is undetectable in the 2 most recent patients on triple-drug antiretroviral therapy.
Of the 5 liver transplant recipients, 4 had a pretransplant diagnosis of HCV infection and 1 presented in fulminant hepatic failure. Four remain alive at 3, 7, 10, and 30 months (again, this report was written in the Summer of 2000, and I don't have an update since then), respectively, with 1 postoperative death due to bacterial sepsis. Two patients developed recurrent HCV infection requiring interferon and ribavirin therapy; liver enzymes were subsequently normalized in both patients. One patient cleared HCV viral RNA on therapy. Another patient developed severe rejection with chronic changes in the allograft after HAART and was abruptly discontinued without changes in the immunosuppressive regimen; the subsequent drop in TAC levels precipitated rejection.
Complications in this series were as follows: 1 death, unrelated to HIV infection 2 episodes of asymptomatic cytomegalovirus infection 2 cases of chronic rejection 1 case of fatty liver possibly related to HAART In addition, the original decision to cover the transplant by fiscal intermediaries was rescinded. The experience with this small series underscores the importance of close monitoring of drug interactions and cooperation between physicians managing the transplant and the HIV disease.
In conclusion, transplantation in this series was not associated with progression of HIV, as evidenced by freedom from opportunistic infections and undetectable viral loads. In all patients, HIV viral loads remained undetectable. TAC requirements on HAART were greatly reduced, with an average dose of 1 mg/week. Survival beyond 24 months after transplantation is possible, with sustained CD4 counts greater than 200. HIV patients retain alloreactivity as demonstrated by the ability to reject their allografts.
Although significant drug interactions occur, these appear to be manageable. HAART remains effective in controlling HIV progression in spite of immunosuppression, at least in the short term. HIV-infected patients have generally been excluded from transplantation. However, recent advances in the management and prognosis of these patients suggest that this policy should be reevaluated. Further information will require carefully designed multicenter trials to determine the feasibility of transplantation in HIV-positive patients. JL
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