There is significant variability amongst transplant centers, Organ Procurement Organizations (OPO), members of public, and patients about organs from Public Health Service increased risk donors. This has therefore required regulatory bodies like Centers for Disease Control and Prevention to formulate policies for transplant centers and OPOs to minimize risk of infectious transmission to recipients of solid-organ transplants from such donors.

Key words : Antibody test, Hepatitis B virus, Hepatitis C virus, Human immunodeficiency virus, Nucleic acid test, Outcomes, Survival

Introduction

Since its inception, transplant medicine has evolved tremendously in selection and treatment of donor and recipients for transplant. The donor selection criteria have expanded from experiences of transplant centers across the world to meet the growing need for organ transplant. In the past decade (2002-2012), there has been a progressive increase of 3000 more solid-organ transplants in the United States (11% increase), but during this decade the list of those awaiting transplant increased by 40 000 more patients (33%).¹ This growing divergence between the number of transplants and number of patients listed awaiting transplant has served as an impetus to expand organ acceptance criteria. These efforts have required balancing the risk of lower donor organ quality with the benefit of minimized waiting list mortality and decreased waiting times. Transplants from expanded criteria donors and donation after cardiac death donors have progressively increased to bridge the gap, and transplant centers have learned how to optimize use of these organs to further increase the expanded donor criteria. In addition to these efforts, there was a subset of organ donors who frequently were not considered for donation: donors deemed at higher risk of infectious transmission through transplant.

The Centers for Disease Control and Prevention (CDC) has endeavored to minimize human immunodeficiency virus (HIV) transmission with recommendations in 1983, 1985, and 1994. In 2013, the Public Health Service (PHS) expanded these guidelines to include screening for hepatitis B virus (HBV) and hepatitis C virus (HCV) in addition to HIV for increased-risk donors.

Centers for disease control and prevention high-risk donor criteria
The 1994, CDC guidelines defined high-risk donors for HIV transmission based on detailed medical and social history from the next of kin and the pre- or posttransfusion blood specimen testing when there was no evidence of hemodilution (Table 1).2 These guidelines for donor screening were revised in June 2013 by PHS to include the risk of HCV and HBV infection and transmission, in addition to HIV.3 The PHS guidelines also reduced the time of increased scrutiny between high-risk behaviors to organ donation from 5 years to 12 months.

Serologic testing and window period
Organ procurement organizations (OPOs) are required by United Network for Organ Sharing (UNOS) to perform serologic antibody testing. However, the accuracy of the testing is limited by the inability to detect infections in the window period, which is the period between the acquisition of infection and antibody formation. Nucleic acid testing (NAT) reduces this window period markedly and increases the sensitivity of screening for HIV, HBV, and HCV (Table 2).⁴

Humar and associates performed a risk-benefit analysis of NAT screening for organ donors, and they concluded that NAT offered an advantage to minimize the risk of HIV, HCV, and HBV transmission and increase organ use by screening only the high-risk donors.⁴ This benefit was greatest with respect to HCV infection due to the substantial reduction in the period. There was insufficient evidence to recommend routine NAT screening for HIV, HCV, and HBV in all potential organ donors. Furthermore, universal NAT testing potentially could be counterproductive for average-risk donors (donors with no identified behavioral risk factors) due to the disadvantages that might include false positive results, increased costs, and organ loss due to withdrawal of consent, logistics, and donor instability.

Orlowski and associates surveyed OPOs; they observed that 47% OPOs performed NAT on all potential organ donors and 28% OPOs performed NAT only on donors thought to be at higher risk of infection due to behavioral history.⁵ Kucirka and coworkers performed a meta-analysis of a PubMed-based search for studies about incidence and prevalence of HIV and HCV in the United States or Canada based on enzyme-linked immunosorbent assay (ELISA) and NAT testing (Table 3).^6,7

Transplant center viewpoint
Ison and Stosor designed an Internet-based survey of United States solid-organ transplant centers to assess the approach in acceptance of organs from high-risk donors, posttransplant surveillance of patients, and opinions about the 1994 PHS guidelines.⁸ They summarized that acceptance of organs from high-risk donors (OHRD) was 2-fold greater for liver (52%) than kidney or small bowel (25%). They also observed that transplant programs were more likely to accept OHRDs with history of injectable drug use or incarceration than other risk factors mentioned in the behavioral patterns of the PHS high-risk donors.

Posttransplant surveillance for recipients of OHRD by serology or NAT was performed routinely for HIV, HBV, and HCV in most transplant centers. Most respondents agreed that high-risk donors should not be excluded from donation, but that OHRD should be considered only for recipients in whom the risk of HIV transmission was less than the transplant. The survey also highlighted that excluding transplants from OHRD likely results in increased deaths for patients awaiting transplant than from transmission of HIV, HCV, or HBV.

After a case of HIV and HCV transmission from a CDC high-risk donor to 4 transplant recipients in 2007, there was heightened concern amongst OPOs and transplant centers that led to the special informed consent by UNOS.⁹ Kucirka and coworkers reported outcomes of a survey of United States transplant surgeons after this reported case.¹⁰ They observed that the response to this highly publicized case was, that 42% surgeons would decrease use of high-risk donors and 17% would increase use of NAT screening, given concerns raised regarding donor HIV and HCV transmission.

Transplant patient viewpoint
The Johns Hopkins transplant group qualitatively analyzed patient viewpoint about CDC high-risk kidney transplants.¹¹ They observed that patients were unfamiliar with the CDC definition of infectious high-risk donors; this and the unpreparedness for transplant resulted in poor acceptance of kidneys from infectious high-risk donors. The lack of appropriate information available to patients regarding infectious high-risk donors, in addition to the social stigmas associated with HIV and HCV, had a large effect on patient decision making. However, after providing patients with adequate information about infectious high-risk donors in focus groups (about the risk of transmission, serologic testing, and the period of HIV, HBV, and HCV), 79% patients reported willingness to consider infectious high-risk donors kidneys. Most patients would be most affected by their own nephrologist’s opinion (the nephrologist who supervises their dialysis care) rather than the recommendations of the transplant nephrologist or transplant surgeon.

Consent
As of August 18, 2008, UNOS policy required transplant centers to obtain special informed consent from patients accepting PHS high-risk organs for transplant, but did not indicate any specific requirements for disclosure of the behavioral risk factors of the donor.¹² This led to variability in the consent process and the type of information shared with the patient. Halpern and colleagues re­commended standardization of the consent process, rather than organ-specific consent as stated by UNOS, which may help maintain autonomy of the patients while making decisions regarding high-risk organs.¹³ They concluded that subdivision of high-risk donors based on behavioral criteria would not help patients make a well-informed decision, but would create a social bias to certain behavioral categories of donors.¹³ They also recommended that UNOS should allow for prospective consent for all patients on the waiting list for the high-risk donors, which would allow sufficient time for patients to analyze the information, further support their autonomy, and avoid last-minute decision making at the time of organ offer. It was suggested that there should be a safeguard mechanism for patients who decline the consent originally and change their mind in the future.

Outcome
In 2011, 10% deceased-organ donors in the United States satisfied the 1994 guidelines for high-risk donors for transmitting infectious diseases and were referred to as CDC high-risk donors. With the revised PHS guidelines of 2013 to identify high-risk donors for transmission of HIV, HCV, and HBV, this cohort now constitutes 20% deceased donors in the United States. Grafts recovered from these donors are healthier, younger, and higher in quality. Kucirka and associates analyzed 29 950 deceased donors who were reported to UNOS from July 2004 to May 2008; they summarized that 12% kidney donors in the PHS/CDC high-risk category were expanded criteria donors, compared with 25.6% for non–high-risk donors (P < .001).¹⁴ Therefore, despite the real but small risk of HIV, HBV, and HCV transmission through transplant, the use of organs from PHS high-risk donors minimizes wait list mortality and likely improves transplant outcomes.

References:

1. Organ Procurement and Transplantation Network. Need continues to grow. U.S. Department of Health & Human Services Web site. http://optn.transplant.hrsa.gov/need-continues-to-grow/. Accessed November 9, 2014.
2. Rogers MF, Simonds RJ, Lawton KE, Moseley RR, Jones WK. Guidelines for preventing transmission of human immunodeficiency virus through transplantation of human tissue and organs. MMWR Recomm Rep. 1994;43(RR-8):1-17.
3. Seem DL, Lee I, Umscheid CA, Kuehnert MJ, United States Public Health Service. PHS guideline for reducing human immuno deficiency virus, hepatitis B virus, and hepatitis C virus transmission through organ transplantation. Public Health Rep. 2013;128(4):247-343.
4. Humar A, Morris M, Blumberg E, et al. Nucleic acid testing (NAT) of organ donors: is the 'best' test the right test? A consensus conference report. Am J Transplant. 2010;10(4):889-899.
5. Orlowski JP, Alexander CE, Ison MG, Rosendale JD, Chabalewski FL. Nucleic acid testing (NAT) for HIV, HBV, and HCV: current practices of 58 US organ procurement organizations (OPOs) [American Transplant Congress abstract 21]. Am J Transplant. 2009;9(suppl S2):197.
6. Kucirka LM1, Sarathy H, Govindan P, et al. Risk of window period HIV infection in high infectious risk donors: systematic review and meta-analysis. Am J Transplant. 2011;11(6):1176-1187.
7. Kucirka LM, Sarathy H, Govindan P, et al. Risk of window period hepatitis-C infection in high infectious risk donors: systematic review and meta-analysis. Am J Transplant. 2011;11(6):1188-1200.
8. Ison MG, Stosor V. Transplantation of high-risk donor organs: a survey of US solid organ transplant center practices as reported by transplant infectious diseases physicians. Clin Transplant. 2009:23 (6):866–873.
9. Ison MG, Llata E, Conover CS, et al. Transmission of human immunodeficiency virus and hepatitis C virus from an organ donor to four transplant recipients. Am J Transplant. 2011;11(6): 1218-1225.
10. Kucirka LM, Ros R, Subramanian AK, Montgomery RA, Segev DL. Provider response to a rare but highly publicized transmission of HIV through solid organ transplantation. Arch Surg. 2011;146(1):41-45.
11. Ros RL, Kucirka LM, Govindan P, Sarathy H, Montgomery RA, Segev DL. Patient attitudes toward CDC high infectious risk donor kidney transplantation: inferences from focus groups. Clin Transplant. 2012;26(2):247-253.
12. U.S. Department of Health & Human Services Web site. http://optn.transplant.hrsa.gov/PublicComment/pubcommentPropSub_220.pdf
13. Halpern SD, Shaked A, Hasz RD, Caplan AL. Informing candidates for solid-organ transplantation about donor risk factors. N Engl J Med. 2008;358(26):2832-2837.
14. Kucirka LM, Alexander C, Namuyinga R, Hanrahan C, Montgomery RA, Segev DL. Viral nucleic acid testing (NAT) and OPO-level disposition of high-risk donor organs. Am J Transplant. 2009;9(3): 620-628.