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Keywords:

  • Deceased organ donor;
  • HIV;
  • hepatitis B;
  • hepatitis C;
  • organ procurement organization;
  • screening;
  • nucleic acid testing;
  • survey

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Disclosure
  9. References
  10. Supporting Information

Although Organ Procurement and Transplantation Network (OPTN) policy requires that all potential deceased organ donors are screened for human immunodeficiency (HIV), hepatitis B (HBV) and hepatitis C (HCV) viruses by serology, no current policy requires the use of nucleic acid testing (NAT) for organ donor screening. An electronic survey was sent to 58 organ procurement organizations (OPO) in the United States to assess current screening practices of potential deceased organ donors. Fifty-seven responses were collected for data analysis; not all respondents answered all questions. All OPOs performed required HIV, HBV and HCV serology screening and 48 (84%) performed confirmatory testing for seropositive donors. Ninety-eight percent, 75% and 97% of OPOs performed prospective HIV, HBV and HCV NAT, respectively. Fifty-two percent and 47% used a transcription-mediated amplification assay for HIV and HCV NAT, respectively. Of the 56 respondents that performed HIV NAT and 55 respondents that performed HCV NAT, 39 tested all donors. Seventeen (32%) OPOs performed confirmatory testing for all HIV-positive NAT results, and 15 (27%) OPOs performed confirmatory testing for all HCV-positive NAT results. Since 2008, the number of OPOs performing NAT has increased and more OPOs are testing all donors.


Abbreviations
Ab

antibody

EIA

enzyme immunoassay

ELISA

enzyme-linked immunosorbent assay

FDA

Food and Drug Administration

HBcAb

hepatitis B core antibody

HBsAg

hepatitis B surface antigen

HBV

hepatitis B virus

HCV

hepatitis C virus

HIV

human immunodeficiency virus

IR

increased risk

NAT

nucleic acid test

OPO

organ procurement organization

OPTN

Organ Procurement and Transplantation Network

PCR

polymerase chain reaction

PDOD

potential deceased organ donor

RIBA

recombinant immunoblot assay

TC

transplant center

TMA

transcription-mediated amplification

TAT

turn-around-time.

Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Disclosure
  9. References
  10. Supporting Information

The Organ Procurement and Transplantation Network (OPTN) currently mandates that all deceased organ donors are screened for human immunodeficiency (HIV) with a U.S. Food and Drug Administration (FDA)-licensed serologic test and hepatitis B (HBV) and hepatitis C (HCV) viruses with a FDA-licensed, approved or cleared serologic test [1]. The well-publicized transmission of HIV and HCV to four organ transplant recipients by a seronegative infected donor in 2007 brought renewed interest to the optimization of donor screening [2]. Although nucleic acid testing (NAT) is not mandated by current OPTN policy, many organ procurement organizations (OPOs) have added NAT to routine serologic testing in order to detect acute infections and thereby, reduce the risk of donor transmission of HIV, HBV and HCV. Since NAT directly detects viral genetic material, the period between when one is infected and when the test can detect the infection (window period) is substantially shortened with NAT compared to serologic tests that detect antibody formation (Table 1) [3-6].

Table 1. Window periods by assay type [3-6]
VirusSerologyNAT1
  • 1

    Based on individual blood donor data.

HIV22 days5–9 days
HBV44 days22 days
HCV66 days3–7 days

In 2008, a survey of 58 U.S. OPOs demonstrated that 78% of OPOs performed NAT on at least some potential deceased organ donors (PDOD) [7]. Only 36% of these OPOs received the NAT result prior to the decision to use organs for transplant [7]. Eight OPOs stated that they would be unable to comply if prospective NAT organ donor screening became mandatory because of the lack of test availability [7]. Another survey of all U.S. OPOs performed in 2008 reported that 51.7% of OPOs performed HIV NAT on all donors, 24.1% performed HBV NAT on all donors, and 48.3% performed HCV NAT on all donors [8]. Twenty-four percent of OPOs never used HIV NAT, 65.5% never used HBV NAT and 31% never used HCV NAT [8].

Controversy over the use of NAT in deceased organ donor screening remains, with critics citing cost, logistical concerns and the possibility of false-positive NAT results as the major barriers to implementation [9]. The proposed “U.S. Public Health Service Guideline for Reducing Transmission of HIV, HBV and HCV through Solid Organ Transplantation” has advocated for a broader use of NAT in deceased organ donor screening, adding further focus on the question of NAT capacity of U.S. OPOs [10]. We therefore conducted this study to assess the current OPO screening practices for HIV, HBV and HCV in the United States.

Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Disclosure
  9. References
  10. Supporting Information

In November 2011, after approval by our Institutional Review Board, a web-based survey was developed to assess the current screening practices by OPOs across the United States. The survey was developed by the co-authors using published data from prior surveys [8] and reviewed by OPO representatives to ensure the questions were clear and the survey would be easy to complete. The survey was disseminated electronically by the Association of Organ Procurement Organizations (AOPO) via SurveyMonkey (http://www.surveymonkey.com) to Executive and Procurement Directors at each of the 58 OPOs in the United States. Respondents consented to the study by answering the first question asking if they agree to participate. Respondents had the option of remaining anonymous or providing contact information. Reminder emails were sent until all OPOs responded; the last response was received in August 2012. Survey questions can be found in the supplemental materials. Questions were asked about potential deceased organ donors (PDODs), defined as a deceased patient who undergoes evaluation by an OPO and has organs offered for the purpose of transplantation. Descriptive statistics were calculated using anonymous survey data.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Disclosure
  9. References
  10. Supporting Information

We received 60 survey responses. One response was blank, and the respondent declined further study participation. Not all respondents answered all questions. Fifty-seven OPOs answered the survey and voluntarily provided identifying information (OPO name and name of individual respondent). The two unidentified responses had data in their answer that matches with public OPO-level data maintained by the OPTN, and one of these respondents appeared to represent the 58th OPO while the other appeared to be a second response from one OPO. Since we were not certain of the origin of the two anonymous responses, they were excluded and we used a total of 57 responses for data analysis. The respondents reported a total of 756 910 death notification calls, 7648 PDODs, and 7107 deceased donors with at least one organ transplanted in 2010.

Nucleic acid testing

Fifty-six (98.2%), 43 (75.4%) and 55 (96.5%) respondents performed prospective HIV, HBV and HCV NAT on at least some PDODs, respectively. The majority of OPOs performed NAT on all PDODs, regardless of risk stratification (Table 2b and Figure 1). OPOs reported a total of 8825 HIV NAT (median 82 [0–1623]), 6482 HBV NAT (median 43 [0–1671]), and 9671 HCV NAT (median 81 [0–1621]) were performed to screen PDODs in 2010.

image

Figure 1. Indications for which OPOs perform nucleic acid testing on potential deceased organ donors.

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Nucleic acid test platforms

Of the 52 OPOs who responded to questions about HIV NAT assay platforms, 27 (51.9%) used a transcription-mediated amplification (TMA) assay and 24 (46.2%) used a polymerase chain reaction assay (PCR) for HIV NAT, and 1 OPO did not specify. Similar numbers are noted for the 51 OPOs that responded regarding HCV NAT platforms: 24 (47.1%) used a TMA assay, 23 (45.1%) used a PCR assay and 4 (7.8%) did not specify test name. Of the 41 OPOs responding about HBV NAT platforms, 19 (46.3%) used a TMA assay and 22 (53.7%) used a PCR assay.

Nucleic acid test result confirmation

Of the responses to questions about confirmation of positive NAT results, 17/54 (31.5%) OPOs performed confirmatory testing for all HIV-positive NAT results and 10 (18.5%) confirmed positive results only some of the time, whereas, 15/55 (27.3%) OPOs performed confirmatory testing for all HCV positive NAT results and 6 (10.9%) did so only sometimes. Nine of 43 (20.9%) OPOs performed confirmatory testing of positive HBV NAT results.

Nucleic acid testing laboratory specifics

Most OPOs are using an out-of-state reference laboratory to perform NAT (Figure 2A). The lack of an available laboratory for HBV NAT and HCV NAT was reported by 5 and 2 OPOs, respectively. When asked to name the laboratory that is used, 17 OPOs named a blood donor testing center that performed NAT for them. NAT results were usually received by the OPO within 12 h (Figure 3). Most OPOs reported they always had the NAT result prior to the transplant center making a decision to accept the PDOD for transplantation (Figure 4).

image

Figure 2. Type of laboratory utilized for screening of potential deceased organ donors. (Panel A) Laboratories utilized for nucleic acid tests (NAT). (Panel B) Laboratories utilized for serologic screening tests.

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image

Figure 3. Nucleic acid test results turn-around times.

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image

Figure 4. Percentage of time that nucleic acid test results are available prior to transplant decision.

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Nucleic acid testing costs and transportation

In 2010, the total amount spent by OPOs on testing PDODs for HIV, HBV and HCV with serology and NAT was a median of $135 000 (range $1700–$7 014 358). The median cost for HIV, HBV and HCV NAT per PDOD was $490 ($30–$2976). OPOs report the median NAT transportation cost per PDOD was $340 ($0–$6000). Twenty-six of the 55 (47.3%) OPOs that responded noted they use plane transportation to laboratories for at least some of their PDOD screening.

Serologic testing

Twenty-one (36.8%) OPOs performed serologic testing (HIV, HBV and HCV combined) on PDODs using a reference laboratory in a different state (Figure 2B). When asked to name the laboratory that is used, 15 (26.3%) OPOs named a blood donor testing center. When asked if they confirmed positive serology results for HIV, HBV and/or HCV, 48 (84.2%) OPOs affirmed that they did, 7 (12.3%) OPOs stated they did not confirm positive results, and 2 (3.5%) respondents did not provide a response. Of the 40 OPOs that gave additional information on confirmatory testing, 27 (67.5%) stated they always reflexively performed a Western Blot for a positive HIV-1/2 enzyme-linked immunosorbent assay (ELISA), whereas three used an immunofluorescence assay. Twenty (50%) OPOs reported they performed a recombinant immunoblot assay (RIBA) to confirm a positive HCV antibody result, although 1 OPO noted they only performed a RIBA if a donor is HCV antibody-positive with a negative NAT result. Seven OPOs commented that they used NAT alone for confirmation of positive serologic results.

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Disclosure
  9. References
  10. Supporting Information

Since the last survey of OPO NAT screening practices conducted in 2008, more OPOs are using NAT to screen potential deceased organ donors for HIV, HBV and HCV (Table 2a). Furthermore, more OPOs are screening all PDODs with NAT, regardless of OPTN-defined increased risk status (Table 2b). Importantly, NAT results are usually now available before the transplant decision is made. These data also reveal that a minority of NAT results are confirmed. Considerable variability between OPOs remains regarding NAT result turn-around time (TAT) and NAT-associated costs, particularly related to transportation of specimens.

Table 2a. OPOs performing NAT for screening of potential deceased organ donors in 2008 and 2010[8]
YearHIV NATHBV NATHCV NAT
200844/58 (76%)20/58 (34%)40/58 (69%)
201056/57 (98%)43/57 (75%)55/57 (97%)
Table 2b. OPOs performing NAT for screening of all potential deceased organ donors, regardless of risk status, in 2008 and 2010[8]
YearHIV NATHBV NATHCV NAT
200830/58 (52%)14/58 (24%)28/58 (48%)
201039/57 (68%)30/57 (53%)39/57 (68%)

The use of NAT to screen PDODs will reduce the possibility of unexpected transmissions of HIV, HBV and HCV to transplant recipients by detecting acute or window period infections, and may also improve the public's opinion on the safety of organ transplantation [2, 9]. NAT advocates also propose that NAT screening could increase utilization of organs from deceased donors, especially organs from donors at increased risk for infectious transmission as defined by OPTN policy [9, 11]. A 2009 consensus conference endorsed a more limited role for NAT in PDOD screening because of concern for: (1) loss of donors and organs due to false-positive NAT results; (2) logistical issues leading to increased TAT of test results; (3) loss of organs or increased cold ischemic time due to longer NAT result TAT; (4) relatively high cost of NAT [9]. The data obtained from this survey updates our knowledge and assessment of the risks and benefits associated with NAT for PDOD screening. Specifically, the data suggest that nearly all OPOs have access to prospective NAT and that NAT is increasingly utilized for screening of all potential deceased organ donors. Most OPOs have reasonably rapid TAT for results and most have results available prior to organ offer. Unfortunately, there is significant variability in the cost of performing the assays and the cost of the transportation associated with conducting NAT. Efforts should be directed at further reducing these costs. Overall, logistical issues surrounding the use of NAT have improved since 2008 and future studies can focus on how NAT affects organ utilization.

Our survey reveals that over half of the OPOs do not perform confirmatory testing of positive NAT results. This is likely due to the current lack of a confirmatory algorithm for the PCR assay. The TMA assay is a multiplex assay which tests for two (Procleix HIV-1/HCV Assay) or three (Procleix Ultrio) viruses initially and if positive, requires a second discriminatory step that determines which of the viruses is present in the donor sample. This allows for internal “confirmation” of an initially positive result. If the initial and discriminatory results are discordant, the package insert has an algorithm for repeating the assay. In contrast, there is no approved confirmatory algorithm for positive PCR results. Therefore, the test is usually interpreted based on one result, which could be falsely negative or positive. Unfortunately, the lack of confirmatory testing of donors with positive NAT results will inhibit the ability to assess the impact of non-reproducibly positive (initially reactive with repeat test result nonreactive) NAT results on organ availability and utilization. These data suggest that retrospective studies alone will not be able to define the true rate of non-reproducibly positive NAT results. Instead, funding will need to be dedicated to conducting prospective studies that re-test residual specimens on NAT-positive donors and determine the true rate of non-reproducibly positive NAT results. Such studies may also inform confirmatory algorithms for existing assays and help determine which of the approved assays, TMA or PCR, provides improved specificity in the setting of deceased donor screening.

The strength of this study is that it captures the most up-to-date information on the current practices of deceased organ donor screening at the 58 U.S. OPOs. The limitations of this study include those intrinsic to survey studies, such as the potential for respondent misinterpretation of questions and recall bias. We did not collect donor-specific details of costs, TAT and results for all individual donors screened in this study. Second, as the respondents had the option of remaining anonymous, we can only say that 57 of the 58 OPOs responded to this survey for certain, although available data suggests that all OPOs responded to the survey.

In conclusion, this study provides insight into the current screening practices of the 58 U.S. OPOs. Most OPOs have the capacity to perform NAT on PDODs and most are performing NAT on all PDODs with acceptable costs and TAT. Confirmatory testing is infrequently performed on donors with positive NAT results. Further studies are needed to define an optimal donor screening strategy.

Acknowledgments

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Disclosure
  9. References
  10. Supporting Information

The authors thank the Association of Organ Procurement Organizations (AOPO), specifically Elling Eidbo and Mark Paster, for their assistance in distributing our survey. A portion of this work was presented at the American Transplant Congress, June 2–6, 2012, Boston, Massachusetts. This work was funded, in part, through the Northwestern University Transplant Outcomes Research Collaborative (NUTORC).

Disclosure

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Disclosure
  9. References
  10. Supporting Information

The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Disclosure
  9. References
  10. Supporting Information

Supporting Information

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Disclosure
  9. References
  10. Supporting Information

Additional Supporting Information may be found in the online version of this article at the publisher's web-site.

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