The AJT Report News and issues that affect organ and tissue transplantation
Many in the transplant community fear that a guideline proposed by the CDC designed to regulate the possibility of transmitting HIV, HBV and HCV through solid-organ transplantation will severely restrict organ availability, inadvertently worsening the overall outcome for transplant recipients.
Can Transplantation Be Zero Risk?
It began as a great idea. Everyone wanted to revise the outdated 1994 guidelines to prevent the transmission of HIV.1 However, somewhere along the way, a chasm developed between the Public Health Service/Centers for Disease Control (PHS/CDC) and the transplant community. While the CDC says the goal of a proposed guideline issued last September (“Public Health Service Guideline for Reducing Transmission of HIV, Hepatitis B Virus (HBV), and Hepatitis C Virus (HCV) Through Solid Organ Transplantation”) is to make transplantation safe from these diseases, the transplant community is afraid the guideline, as written, will limit organ transplants only to instances in which very little or no apparent risk exists.2
Last August, the American Society of Transplant Surgeons (ASTS), the American Society of Transplantation (AST), the Association of Organ Procurement Organizations (AOPO) and the North American Transplant Coordinators Organization (NAT-CO) wrote to the Department of Health and Human Services (HHS) “quite simply, as the consequence of a misguided effort to completely eliminate all risk of disease transmittal, more patients will die of organ failure than will be saved by avoiding donor-derived infection.”3
Some in the transplant community also say the guidelines are unrealistic. “Some people want a world that, quite truthfully, we don't live in,” says Timothy Pruett, MD, a University of Minnesota transplant surgeon who has been very engaged in the processes of donor history and testing, as well as in the risk of disease transmission. “We can reduce the number of disease transmissions by using more and more stringent tests. But the ultimate impact is that it will restrict organ availability and we’ll have many more patient deaths.”
“If the public looks at this as making transplantation totally safe from infectious disease, then it has to be a false sense of security,” says Tim Brown, president of AOPO.
Back to the Drawing Board
After the guideline's public comment period ended, the CDC made changes to the original draft, taking into consideration comments from transplant professionals, societies and patients (See “Selected Public Comments on the Proposed Rule,” next page). In an effort to bring the community back to the table, the CDC will meet with transplant representatives to discuss the revised document, says Matthew Kuehnert, MD, director of the CDC's Offi ce of Blood, Organ and Tissue Safety.
There is a lot to discuss. Public comments to HHS and the CDC say the guideline is not supported by consensus, the cost for increased testing and the limited amount of time to conduct tests are problematic, and some of the suggested risk factors (such as “more than two sexual partners”) are unrealistic. “Most of us are concerned that all of the very strong recommendations as written are based on what we feel, rather than what we know,” says Dr. Pruett. “The way it's come out is not so much evidence-based as opinion-based. And, it doesn't refl ect the differences in opinion, which I find a bit disturbing.”
- • The proposed guideline would impose stringent testing to eliminate the possibility of transmitting HIV, HBV and HCV through solid-organ transplantation.
- • Many in the transplant community fear the guideline, as written, will limit transplant only to instances in which very little or no apparent risk exists, restricting organ availability.
- • Some public comments say the guideline is not supported by consensus, the cost for increased testing and the limited amount of time to conduct tests are problematic, and some of the suggested risk factors are unrealistic.
What Happened to the Expert Feedback?
Several transplant professionals contacted by the “The AJT Report” said the CDC did not include the recommendations of an expert panel and review committee in the September version of the proposed guideline. According to these sources, the CDC listened to transplant experts over a two-year period, from 2009 through 2011, and then presented a draft for interagency review to the HHS. At that point, according to the August AST/ASTS/AOPO/ NATCO letter to the HHS, “virtually all of the external expert reviewers indicated that the changes made during the course of the interagency review were not consistent with the little evidence that is available, and that the document, as modified, did not represent their expert opinion.”3
SELECTED PUBLIC COMMENTS ON THE PROPOSED GUIDELINES
Following are a selection of public comments to the CDC's proposed “Public Health Service Guideline for Reducing Transmission of Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), and Hepatitis C Virus Through Solid Organ Transplantation.”
For some potential donors, centers will be reluctant to accept donor organs if the OPO or transplant center cannot obtain testing results prior to the transplant.
The draft guideline refl ects the CDC's focus on complete elimination of the risk of disease transmittal, without adequate consideration of the need to balance this objective against the need to increase the availability of organs for transplantation
—ASTS, AST, AOPO, NATCO
Strong recommendations with little-to-no evidence basis are contained in the document, including several living-donor related recommendations that were never reviewed by the Expert Panel or Review Committee.
—Northwestern University Feinberg School of Medicine
Regarding the requirement to NAT test all donors for HIV and HCV, we feel [the guidelines will] increase the cost of transplantation while providing little to no benefit.
—LifeNet Health, Virginia Beach, Va.
We are concerned that the recommendation in its present form may lead to reimbursement denial by the insurance companies and legal liability claims by the lawyers.
—American Association for the Study of Liver Diseases
The document in its current form contains recommendations that are very concerning, notably the requirements for universal NAT testing of prospective deceased donors.
—International Society for Heart and Lung Transplantation
Additional comments to the proposed guidelines can be found at http://www.regulations.gov .
As a result, the transplant societies and organizations who had originally supported the PHS/CDC efforts took their names off the proposed guideline.
According to sources contacted for this article, the entire issue of risk is a trade-off. While most transplantation professionals believe a little risk is acceptable in order to improve the donor pool, the result may be imperfection in terms of disease surveillance. “What the transplant community is looking for is consistency and optimizing safety, but not zero risk,” says Emily Blumberg, MD, chair of the United Network for Organ Sharing/Organ Procurement and Transplantation Network (UNOS/ OPTN) Disease Transmission Advisory Committee and an infectious disease specialist at the University of Pennsylvania. “We don't think transplantation is zero risk.”
Nucleic Acid Testing
The PHS/CDC proposed guideline strongly advocates the use of nucleic acid testing (NAT) to identify HIV and HCV. However, NAT is not a standard practice at organ procurement organizations, and test platforms vary between sites, according to AOPO's Brown. He referred to a recent article in Progress in Transplantation, in which Shafer and colleagues said the number of false-positive HIV tests would dramatically increase with NAT, resulting in hundreds or thousands of unnecessary deaths due to discarded, healthy organs.4
In contrast, a letter to the CDC from OneLegacy, the nation's largest OPO and the one with the longest history of NAT testing, says that “contrary to prevailing opinion that NAT produces many false-positive results leading to loss of organs, these events are rare in well-designed laboratories with properly chosen assays.”5
OneLegacy contends that the testing can also be critical for patient peace of mind. “It becomes enormously problematic for transplant professionals to adequately explain the implications of ‘high risk’ to potential recipients and their families,” according to OneLegacy's letter. “More often than not, such discussions result in the potential recipient's refusal of an otherwise acceptable and life-saving organ.”
Jay A. Fishman, MD, associate director of Massachusetts General Hospital Transplantation Center in Boston, kept his name on the proposed guideline when others withdrew. He tells “The AJT Report” that the guidelines indicate the potential benefits of increased use of NAT for informed consent. For example, he notes that a heart recipient might be offered an HBV core-positive but DNA-negative organ.
Dr. Kuehnert points out a portion of the guideline that some readers may have missed. “We make it very clear that if there is not time to do a test before a transplant, and the transplant is life-saving, then do the transplant and test later,” to manage any disease that might have been transmitted.
Overall, Dr. Kuehnert says he is struck by the passionate opposition from the transplant community. However, he understands their concern and says, “We’ve gotten plenty of useful comments that will help in revision of the guidelines. And, there is no question that there will be changes made.”
- 1 Centersfor Disease Control and Prevention. Guidelines for prevention of transmission of human immunodeficiency virus through transplantation of human tissue and solid organs. MMWR 1994; 43: 1–17.
- 2 Centers for Disease Control and Prevention. Public Health Service guideline for reducing transmission of human immuno deficiency virus(HIV), hepatitis B virus(HBV), and hepatitis C virus (HCV) through solid organ transplantation. Docket CDC-2011-0011. http://federalregister.gov/a/2011-30205. Accessed January 28, 2012.
- 3 American Society of Transplant Surgeons, American Society of Transplantation, Association of Organ Procurement Organizations, and North American Transplant Coor-dinators Organization(NATCO). Letter to Howard Koh, MD, MPH, Assistant Secretary for Health, Department of Health and Human Services. August 23, 2011. http://www.asts.org/Tools/Download.aspx?fid=1438. Accessed January 28, 2012.
- 4 Zero risk tolerance costslives:loss of transplantable organs due to human immuno deficiency virus nucleic acid testing of potential donors. Prog Transplant 2011; 21: 236–247. , , , , , .
- 5 One Legacy. Position Statment on Proposed CDC High Risk Organ Donor Guidelines. December 21, 2011.
Organ-Safety Efforts From Across the Pond…
Many countries in the European Union (EU) have their own, sometimes strict, guidelines to prevent transmission of infectious disease in donated solid organs. While the European Centre for Disease Prevention and Control (ECDC) has not worked directly on this issue, ECDC spokesperson Romit Jain says the EU passed legislation on organ donation safety in 2010, which becomes national law for EU member states by the end of August 2012.1 The legislation stipulates the minimum data set that should be obtained for each donation, including HIV, HBV and HCV, but leaves the decision on whether to use the donated organ or tissue to the physician in charge.
Internationally, the World Health Organization (WHO) and the Italian Cen-tro Nazionale Trapianti (CNT) are developing a first-ever library of international adverse events and reactions in transplantation.2 Called the NOTIFY Library, this interactive website is expected to be active sometime this year.
- 1 Directive of the European Parliament and the Council 2010/45/EU0. http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2010:207:0014:0029:EN:PDF. Accessed January 28, 2012.
- 2 Global library of adverse events and reactions. Am J Transplant 2011; 11: 2267–2268. .