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Update in Gastroenterology and Hepatology

Ronald L. Koretz, MD; and Timothy O. Lipman, MD
[+] Article and Author Information

From Olive View-UCLA Medical Center, Sylmar, California, and the Veterans Affairs Medical Center, Washington, DC.


Potential Financial Conflicts of Interest: None disclosed.

Requests for Single Reprints: Ronald Koretz, MD, Department of Medicine, Olive View-UCLA Medical Center, 14445 Olive View Drive, Sylmar, CA 91342; e-mail, rkoretz@ladhs.org.

Current Author Addresses: Dr. Koretz: Department of Medicine, Olive View-UCLA Medical Center, 14445 Olive View Drive, Sylmar, CA 91342.

Dr. Lipman: Gastroenterology/Hepatology/Nutrition Section, Department of Medicine, Veterans Affairs Medical Center, 50 Irving Street NW, Washington, DC 20422.


Ann Intern Med. 2005;143(5):347-354. doi:10.7326/0003-4819-143-5-200509060-00010
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We have several goals for this update, the most important one being to review the pertinent literature in gastroenterology and hepatology that appeared in 2004. Some of these papers contain important resource utilization implications that need debate. Others will provide opportunities to consider topics about critical reading of the literature.

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Liver Transplantation in HIV-Infected Individuals
Posted on September 28, 2005
Margaret V Ragni
University of Pittsburgh
Conflict of Interest: None Declared

To the Editor:

We were pleased that Annals chose our recent paper (1) concerning liver transplantation in HIV-infected individuals for the 2005 "Update in Gastroenterology and Hepatology" (2), but would like to clarify a few points about our paper and this evolving field.

Contrary to the review by Drs. Koretz and Lipman, this was a prospective study of consecutively enrolled HIV-infected liver transplant recipients, who underwent the procedure by the same listing criteria as HIV-negative recipients. We felt compelled to carry out this study i) because significant advances had occurred in HIV treatment with highly active antiretroviral therapy (HAART); ii) because HIV-infected individuals were surviving AIDS to die of end-stage liver disease (3); and iii) because our past studies had suggested liver transplantation was unsafe related to the immunodeficiency associated with both anti-rejection immunotherapy and HIV infection (pre-HAART)(4).

We, therefore, tested the hypothesis that HIV-infected transplant recipients treated with HAART have comparable survival to HIV-negative recipients. Subjects were accepted for study based on standard listing criteria used for HIV-negative individuals, as well as evidence of compliance with and responsiveness to HAART. It should be noted that the average MELD score among HIV-infected transplant recipients in this study, 15, in fact, did not differ from that, 16, among HIV-negative patients transplanted in U.S.(5).

Moreover, our findings were the impetus for development of the NIAID- sponsored, Solid Organ Transplant in HIV Study, which will determine the safety and efficacy of liver transplantation in individuals with HIV infection. If our findings are confirmed in this multi-center study, then we believe HIV infection should no longer be an absolute contraindication to transplantation.

While immunosuppression continues to be associated with significant morbidity in both HIV-positive and HIV-negative transplant recipients, it should be recognized that until the recent development of new antiviral agents, hepatitis B virus infection was also a relative contraindication to liver transplantation.

Finally, decisions regarding organ allocation in HIV infection, based on cost or utility, are flawed: the same argument could be made regarding organ allocation in individuals with HCV infection, hepatocellular carcinoma, diabetes, chronic pulmonary disease, or by age or MELD score. Thus, the conclusion by Drs. Koretz and Lipman that transplantation is less effective or less warranted in HIV-infected individuals is simply incorrect and unjustified.

References:

1. Ragni MV, Belle SH, Im K, et al. Survival of human immunodeficiency virus-infected liver transplant recipients. J Infect Dis 2003; 188: 1412-20

2. Koretz RL, Lipman TO. Should HIV Infection be a contraindication to transplantation? Update in Gastroenterology and Hepatology. Ann Intern Med 2005; 143: 352.

3. Ragni MV, Bontempo FA, Lewis JH. Organ transplantation in HIV- positive patients with hemophilia. N Engl J Med 1990; 322: 1886-7.

4. Ragni MV, Belle SH. Impact of immunodeficiency virus infection on progression to end-stage liver disease in individuals with hemophilia and hepatitis C virus infection. J Infect Dis 2001; 183: 1112-15.

5. Stell DA, McAlister VC, Thorburn D. A comparison of disease severity and survival rates after liver transplantation in the United Kingdom, Canada, and the United States. Liver Transpl 2004; 10: 908-10.

Conflict of Interest:

None declared

HIV-infected patients should not be excluded from transplantation
Posted on October 5, 2005
Scott D. Halpern
University of Pennsylvania School of Medicine
Conflict of Interest: None Declared

To the Editor:

In reviewing a recent study by Ragni and colleagues(1) comparing outcomes among selected HIV-positive and HIV-negative patients who received liver transplants, Koretz and Lipman conclude that "these data do not provide a compelling argument to change our policy of making HIV infection a contraindication to liver transplantation.(2)" We agree that interpretation of Ragni and colleagues' results is hindered by weaknesses of the study. Thus, as Koretz and Lipman suggest, this study has limited ability to inform policy on transplantation in HIV-infected patients.

However, despite our agreement on the limited influence of the study by Ragni and colleagues, we hold a substantially different view of what the default policy should be regarding transplantation among HIV-infected patients. Unless or until strong evidence emerges that HIV-infected patients have markedly inferior outcomes after transplantation as compared to uninfected hosts, there will remain no compelling reason to exclude HIV -infected patients from transplantation candidacy.(3) Proof of equivalence in outcomes has never been required prior to considering any patient group for transplantation. Moreover, liver transplantation is routinely performed among patients infected with the hepatitis C virus despite clear evidence that such patients have inferior outcomes.(4, 5) We therefore suggest that patients with well-controlled HIV disease be considered for transplantation of all organs, not because of limited evidence that it works, but because there is no evidence that it does not, and thus it would be discriminatory to exclude HIV infected patients from this life-saving intervention.(3)

1. Ragni MV, Belle SH, Im K, et al. Survival of human immunodeficiency virus-infected liver transplant recipients. Journal of Infectious Diseases. 2003;188(10):1412-20.

2. Koretz RL, Lipman TO. Update in gastroenterology and hepatology. Ann Intern Med. 2005;143:347-54.

3. Halpern SD, Ubel PA, Caplan AL. Solid organ transplantation in HIV -infected patients. N Engl J Med. 2002;347:284-7.

4. Forman LM, Lewis JD, Berlin JA, Feldman HL, Lucey MR. The association between hepatitis C infection and survival after orthotopic liver transplantation. Gastroenterology. 2002;122:889-96.

5. Nair S, Eustace J, Thuluvath PJ. Effect of race on outcome of orthotopic liver transplantation: a cohort study. Lancet. 2002;359:287-93.

Conflict of Interest:

None declared

Reply from authors
Posted on November 4, 2005
Ronald L. Koretz
Olive View-UCLA Medical Center and Veterans Affairs Medical Center, Washington D.C.
Conflict of Interest: None Declared

We thank Dr. Ragni and colleagues for clarifying the prospective nature of their study. This was not apparent to us from their Methods section (1), which stated: "24 subjects with HIV infection and ESLD who fulfilled standard listing criteria for liver transplantation underwent OLTX at 5 institutions".

Ragni et al state that there were no differences between the MELD scores of their patients and HIV-negative ones. However, in the accompanying editorial (2), Dr. Fishman cited a 2002 UNOS report indicating that the median MELD score during the past year in patients without acute hepatic failure was 22.16. Dr. Fishman also noted that, in regions with severe organ shortages, transplantation may not occur until the MELD score reached 25-35.

Ragni et al concluded that the survival of HIV-positive liver transplant recipients does not differ from that of HIV-negative ones. However, the length of followup in their 24 recipients was limited; only 3 were followed for at least 36 months. The 5-year survival rate was only 36%, compared to 71% in the HIV-negative cohort. Even if this difference was not statistically significant, the numbers are small and the arithmetic difference is large. Failure to prove a difference does not assure the presence of equivalence.

The major difference between Drs. Ragni et al and us relate to applicability of the findings in the world of transplantation. As a society, we will have to make decisions regarding resource utilization for health care, since those resources (money and organs) are not unlimited. If we cannot use cost and efficacy, what are we to use? Even if we accept the figure of $50,000 per life-year saved (and that figure, if applied to the entire population, is higher than the gross domestic product), organ transplantation in anybody is arguably too expensive. If two otherwise comparable patients (differing only in HIV status) are competing for one available organ, and even if the long-term outcomes were the same, the additional cost of the HIV therapy will add more expense to the post- transplantation care. (The data from Ragni et al certainly cannot be interpreted to infer that the post-transplantation course of the HIV- positive individual is better.) If health care resources were infinite, the only issue would be to avoid harm. Since resources are limited, we have to be prepared to make judgments about where to do good.

References 1. Ragni MV, Belle SN, Im KA, Neff G, Roland M, Stock P, Heaton N, Humar A, Fung JF. Survival of human immunodeficiency virus-infected liver transplant recipients. J Infect Dis 2003; 188:1412-1420 2. Fishman JA. Transplantation for patients infected with human immunodeficiency virus: no longer experimental but not yet routine. J Infect Dis 2003; 188:1405-1411

Conflict of Interest:

None declared

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