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Keywords:

  • Donor screening;
  • guidelines;
  • HBV transmission risk;
  • HCV transmission risk;
  • HIV transmission risk;
  • infectious disease transmission;
  • organ donation;
  • organ transplant recipients;
  • organ transplantation;
  • recipient testing

Abstract

  1. Top of page
  2. Abstract
  3. Executive Summary
  4. Recommendations
  5. Recommendations for Further Study
  6. Acknowledgments
  7. Disclosures
  8. References

The intent of the PHS guideline is to improve organ transplant recipient outcomes by reducing the risk of unexpected HIV, HBV and HCV transmission, while preserving the availability of high-quality organs. An evidence-based approach was used to identify the most relevant studies and reports on which to formulate the recommendations. This excerpt from the guideline comprises (1) the executive summary; (2) 12 criteria for assessment of risk factors for recent HIV, HBV and HCV infection; (3) 34 recommendations on risk assessment (screening) of living and deceased donors; testing of living and deceased donors; informed consent discussion with transplant candidates; testing of recipients pre- and posttransplant; collection and/or storage of donor and recipient specimens; and tracking and reporting of HIV, HBV and HCV; and (4) 20 recommendations for further study. For the PHS guideline in its entirety, including the background, methodology and primary evidence underlying the recommendations, refer to the source document in Public Health Reports, accessible at http://www.publichealthreports.org/issuecontents.cfm?Volume=128&Issue=4. For more in-depth information on the evidence base, including tables of all study-level data, refer to Solid Organ Transplantation and the Probability of Transmitting HIV, HBV or HCV: A Systematic Review to Support an Evidence-Based Guideline, accessible at http://stacks.cdc.gov/view/cdc/12164/.


Abbreviations
EDTA

ethylenediaminetetraacetic acid

FDA

Food and Drug Administration

GRADE

Grading of Recommendations, Assessment, Development and Evaluation

HBV

hepatitis B virus

HCV

hepatitis C virus

HIV

human immunodeficiency virus

NAT

nucleic acid testing

OPO

organ procurement organization

OPTN

Organ Procurement and Transplantation Network

PHS

Public Health Service.

Executive Summary

  1. Top of page
  2. Abstract
  3. Executive Summary
  4. Recommendations
  5. Recommendations for Further Study
  6. Acknowledgments
  7. Disclosures
  8. References

This guideline supersedes the 1994 U.S. Public Health Service (PHS) Guidelines for Preventing Transmission of Human Immunodeficiency Virus through Transplantation of Human Tissue and Organs, hereafter referred to as the 1994 PHS guidelines [1, 2]. The most significant changes are:

  • Expanding the guideline to include hepatitis B virus (HBV) and hepatitis C virus (HCV), in addition to human immunodeficiency virus (HIV).
  • Using factors known to be associated with an increased likelihood of recent HIV, HBV or HCV infection to identify potential donors who may be at increased risk for transmitting infection.
  • Limiting the focus to organs and blood vessel conduits recovered for organ transplantation because the Food and Drug Administration (FDA) implemented more comprehensive regulations for human cell and tissue products [3].

As with the 1994 PHS guidelines, the recommendations relate to adult and pediatric donors who are living or deceased, as well as transplant candidates and recipients. This guideline is not intended to assess infectious risks beyond HIV, HBV and HCV.

This document provides guidance to organ procurement organization (OPO) personnel; transplant center personnel, including physicians, nurses, administrators and clinical coordinators; laboratory personnel responsible for testing and storing donor and recipient specimens and individuals responsible for developing, implementing and evaluating infection prevention and control programs for OPOs and transplant centers.

The Health Resources and Services Administration, a PHS agency, oversees organ procurement and transplantation in the United States through its oversight of the Organ Procurement and Transplantation Network (OPTN). The United Network for Organ Sharing is the entity that currently serves as the contractor to operate the OPTN. In writing this guideline, the PHS sought assistance from public and private health professionals and representatives of transplantation, organ recovery, public health and other organizations.

Unexpected transmission of HIV, HBV and HCV through organ transplantation is a patient safety and public health issue. Such events, although rare, can result in serious illness and death in organ recipients who are immunosuppressed, particularly when transmission is unexpected. Notification of state public health authorities is required when donors or recipients are identified as newly infected with HIV, HBV or HCV. When an organ recipient is newly infected and the infection is suspected of being donor-derived, immediate notification of institutions that recovered or transplanted organs and tissues from the same donor is important. Such notification may not only allow for early treatment of newly infected recipients to minimize the impact of the disease, but also prevent further distribution or implantation of potentially infected tissues. Unexpected transmission of HIV, HBV and HCV from infected donors has been reported in heart, liver, kidney and pancreas recipients [4-14].

The objective of this guideline is to improve organ transplant recipient outcomes by reducing the risk of HIV, HBV and HCV transmission, keeping in mind that transplantation can never be free of this risk. Given the large discrepancy between the number of candidates on the transplant list and the number of organs available, recommendations in this document may differ from policies or regulations in the setting of blood or tissue donation, due to different risk and benefit considerations for organ transplantation. Even though attempts should be made to ensure the highest level of safety, organ donor and recipient selection practices and policies should not be restrictive, considering the clinical need. Therefore, informed decision-making is an important part of this process for transplant clinicians and their patients.

To evaluate the evidence on reducing transmission of HIV, HBV and HCV, we examined data addressing 10 key questions within five major topic areas (Table 1). A sixth topic area includes questions addressed by expert opinion (Table 2). We drew upon subject-matter experts to draft summaries related to these questions, as a preliminary scan of the literature showed that a systematic review would likely yield insufficient data.

Table 1. Major topic areas and key questions for the systematic literature review concerning HIV, HBV and HCV transmission through organ transplantation
Major topic area of the guidelineQuestion for systematic review
  1. HIV, human immunodeficiency virus; HBV, hepatitis B virus; HCV, hepatitis C virus.

I. Probability of transmission of HIV, HBV or HCV through organ transplantation1. What are the prevalence and incidence rates of HIV, HBV and HCV among potential organ donors?
 2. What are the rates of transmission to recipients from donors infected with HIV, HBV or HCV? Do the rates vary by the organ transplanted or when the donor was infected?
II. Methodology to better estimate donor infection with HIV, HBV or HCV3. What behavioral risk factors are associated with an increased probability of infection with HIV, HBV or HCV? What is the prevalence of these characteristics among potential organ donors?
 4. What nonbehavioral factors are associated with an increased probability of infection with HIV, HBV or HCV? What is the prevalence of these factors among potential organ donors?
 5. What are the test characteristics of the screening methods available to detect HIV, HBV and HCV in potential organ donors? Do test characteristics differ in particular populations and with donor clinical status (e.g. donation after brain death versus donation after cardiac death OR adult versus pediatric donors)?
III. Donor interventions to decrease transmission of HIV, HBV or HCV from infected donors6. Which donor interventions reduce the probability of pathogen transmission from an organ donor infected with HIV, HBV or HCV to a previously uninfected recipient?
IV. Potential risks and benefits of transplanting, or not transplanting, organs from donors positive for HIV, HBV or HCV7. How do the clinical outcomes of recipients of organs from donors infected with HIV, HBV or HCV compare to those who remain on the transplant list?
V. Potential risks and benefits of transplanting, or not transplanting, organs from donors with risk factors for HIV, HBV or HCV8. How do the clinical outcomes of transplant recipients who receive organs from donors with behavioral or nonbehavioral risk factors compare to those who remain on the transplant list?
 9. What is the impact of excluding potential organ donors with behavioral or nonbehavioral risk factors on the organ donor pool?
 10. What is the impact of false positive tests on the organ donor pool?
Table 2. Major topic area and questions addressed by expert opinion relevant to concerning HIV, HBV and HCV transmission through organ transplantation
Major topic area of the guidelineQuestion addressed by expert opinion
  1. HIV, human immunodeficiency virus; HBV, hepatitis B virus; HCV, hepatitis C virus.

VI. Approaches to informing recipients about the risks of HIV, HBV and HCV transmission and evaluation for possible exposure posttransplantation1. How and when should informed consent be obtained from potential recipients to help them consider the risks (i.e. probability of acquiring the disease and consequences of disease acquisition) of donor-derived HIV, HBV and HCV?
 2. When should testing of a transplant recipient be done to detect HIV, HBV and HCV transmission from the donor?
 3. How should donor and recipient specimens be collected and stored for potential investigation of donor-derived HIV, HBV and HCV infection?

Recommendations related to the 10 key questions were based on a targeted systematic review of the best available evidence, with explicit links between the evidence and recommendations. To accomplish this review, we used a modified Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach for evaluating quality of evidence and determining strength of recommendations [15-19]. If weighing the critical outcomes for a key question resulted in a net benefit or a net harm, then a Category I recommendation was formulated to recommend strongly for or against the given intervention, respectively. If weighing the critical outcomes for a key question resulted in a trade-off between benefits and harms, then a Category II recommendation was formulated to recommend that providers or institutions consider the intervention when deemed appropriate.

In addition to a category rating, recommendations were also assigned a level rating (A through D) to reflect the quality of the evidence base underlying the recommendations. Level A represents high- to moderate-quality evidence and Level B represents low- to very low-quality evidence. No recommendations were assigned a Level A rating. Level C represents required practices by state or federal regulations, regardless of evidence quality. Level D represents recommendations from previously published guidelines or reports for topics not directly addressed by the systematic review of the evidence, but deemed critical to the target user; in this level, critical outcomes were determined to result in net benefits, regardless of evidence quality.

It is important to note that the strength of a Category IA recommendation is equivalent to that of a Category IB, IC or ID recommendation; it is only the quality of the evidence underlying the Category IA recommendation that makes it different.

Recommendations related to the three expert opinion questions were based on the expert opinion summaries (in the source document) and are designated either as IB if they represent a strong recommendation or IIB if they represent a weak recommendation.

Areas in need of further research identified during the evidence review, from public comment and during review following public comment, are outlined in the Recommendations for Further Study section. This section addresses gaps that affected the ability to adequately address many of the key questions; therefore, specific recommendations either could not be supported because of the absence of available evidence or were supported by low-quality evidence. These recommendations provide guidance for new research or methodologic approaches that should be used in future studies.

Recommendations

  1. Top of page
  2. Abstract
  3. Executive Summary
  4. Recommendations
  5. Recommendations for Further Study
  6. Acknowledgments
  7. Disclosures
  8. References

There are 12 criteria listed in this section to assess donor risk for HIV, HBV and HCV infection. Eleven of the criteria are to evaluate infection risk for all three pathogens collectively; one criterion is to evaluate infection risk for HCV only. The 34 recommendations are numbered and grouped into sections as follows: risk assessment (screening) of living and deceased donors (recommendations 1–5); testing of living and deceased donors (recommendations 6–9); informed consent discussion with transplant candidates (recommendations 10–15); testing of recipients pre- and posttransplant (recommendations 16–20); collection and/or storage of donor and recipient specimens (recommendations 21–25) and tracking and reporting of HIV, HBV and HCV (recommendations 26–34).

If a recommendation was based on evidence for one of the 10 key questions, the key question is referenced (e.g. Key Question 3). If a recommendation was based on evidence for one of the three expert opinion questions, the expert opinion question is referenced (e.g. Expert Opinion—Question 1). Additional information on categorizing the recommendations can be found in Table 3.

Table 3. Categorization scheme applied to the 34 recommendations concerning HIV, HBV and HCV transmission through organ transplantation
CategoryRecommendation strength and quality of evidence
  1. HIV, human immunodeficiency virus; HBV, hepatitis B virus; HCV, hepatitis C virus.

Category IAStrong recommendation supported by high- to moderate-quality evidence suggesting net clinical benefits or harms
Category IBStrong recommendation supported by low- to very low-quality evidence suggesting net clinical benefits or harms
Category ICStrong recommendation required by state or federal regulation, regardless of evidence quality
Category IDRecommendation from a previously published guideline or report not linked to a key question and no systematic review of the literature performed, but the critical outcome considered was determined to result in a net benefit, regardless of evidence quality
Category IIAWeak recommendation supported by high- to moderate-quality evidence suggesting a trade-off between clinical benefits and harms
Category IIBWeak recommendation supported by low- to very low-quality evidence suggesting a trade-off between clinical benefits and harms

Throughout the recommendations, the following conditions and definitions of terms are applicable:

  • As blood vessels conduits are classified as organs, recommendations relating to recovered or transplanted organs also apply to these vessel conduits.
  • A presumed HBV-infected donor is defined as being positive for hepatitis B surface antigen (HBsAg), antibody to hepatitis B core antigen (anti-HBc) and/or HBV by nucleic acid testing (NAT). A presumed HBV-infected transplant candidate is defined as being positive for HBsAg, immunoglobulin M antibodies to HBc (IgM anti-HBc) and/or HBV by NAT. (A transplant candidate who is positive only for immunoglobulin G antibodies to HBc [IgG anti-HBc] could be a chronic carrier with HBsAg at an undetectable level or could have cleared the virus.)
  • A presumed HCV-infected donor or transplant candidate is defined as being positive for antibodies to hepatitis C virus (anti-HCV) and/or HCV by NAT.
  • The term “increased risk” applies to donors at higher-than-average risk for HIV, HBV and HCV infection, or for only one of the pathogens when specifically identified.
  • The recommendations in this guideline that cite increased risk donors are referring to donors with one or more of the risk factors for HIV, HBV or HCV infection listed in the next section.

Risk factors for recent HIV, HBV or HCV infection

This section lists the risk factors associated with an increased likelihood of recent HIV, HBV or HCV infection (Table 4). The initial list of risk factors identified from the literature review was modified by subject-matter experts on HIV and hepatitis due to the paucity of evidence for recent (i.e. incident) infection from the studies that met inclusion criteria. Development of this list took into consideration that (1) certain risk factors are probably markers for other factors identified in the systematic review; (2) scientific evidence associating certain factors with the pathogens exists, but may not have met the inclusion criteria of the systematic review and (3) certain studies were of insufficient quality to draw conclusions.

Table 4. Factors identified in the literature to be associated with increased likelihood of recent HIV, HBV or HCV infection
  1. HIV, human immunodeficiency virus; HBV, hepatitis B virus; HCV, hepatitis C virus; MSM, men who have sex with men.

Risk factors for HIV, HBV and HCV infection
1. People who have had sex with a person known or suspected to have HIV, HBV or HCV infection in the preceding 12 months
2. Men who have had sex with men (MSM) in the preceding 12 months
3. Women who have had sex with a man with a history of MSM behavior in the preceding 12 months
4. People who have had sex in exchange for money or drugs in the preceding 12 months
5. People who have had sex with a person who had sex in exchange for money or drugs in the preceding 12 months
6. People who have had sex with a person who injected drugs by intravenous, intramuscular or subcutaneous route for nonmedical reasons in the preceding 12 months
7. A child who is ≤18 months of age and born to a mother known to be infected with, or at increased risk for, HIV, HBV or HCV infection
8. A child who has been breastfed within the preceding 12 months and the mother is known to be infected with, or at increased risk for, HIV infection
9. People who have injected drugs by intravenous, intramuscular or subcutaneous route for nonmedical reasons in the preceding 12 months
10. People who have been in lockup, jail, prison or a juvenile correctional facility for more than 72 consecutive hours in the preceding 12 months
11. People who have been newly diagnosed with, or have been treated for, syphilis, gonorrhea, Chlamydia or genital ulcers in the preceding 12 months
Risk factor for HCV infection only
12. People who have been on hemodialysis in the preceding 12 months

Donors who meet one or more of criteria 1–11 should be identified as being at increased risk for recent HIV, HBV and HCV infection. Each factor listed reflects increased risk of all three pathogens as an aggregate, as there is overlap of associated risk, even though each factor does not convey risk from all pathogens equally. The first six risk factors address sexual contact; the definition of “had sex” refers to any method of sexual contact, including vaginal, anal and oral contact. Donors who meet criterion 12 should be identified as being at increased risk for recent HCV infection only.

Risk assessment (screening) of living and deceased donors

  1. All living potential donors and individuals interviewed about deceased potential organ donors (e.g. next of kin, life partner, cohabitant, caretaker, friend or primary treating physician) should be informed of the donor evaluation process, including the review of medical and behavioral history, physical examination and laboratory tests to identify the presence of infectious agents or medical conditions that could be transmitted by organ transplantation (Category ID).
  2. To ascertain whether potential organ donors are at increased risk for HIV, HBV or HCV infection, living donors or individuals contacted about deceased donors, should be interviewed in a confidential manner about behaviors that may have increased the potential donor's probability of having HIV, HBV or HCV infection (Category IB; Key Questions 3 and 4).
  3. Living potential donors with behaviors associated with an increased risk of acquiring HIV, HBV or HCV identified during evaluation should receive individualized counseling on specific strategies to prevent exposure to these viruses during the time period prior to surgery (Category ID).
  4. If a potential donor is ≤18 months of age or has been breastfed within the preceding 12 months, the birth mother, if available, should be interviewed about behaviors that may have placed her at risk for HIV, HBV or HCV infection (Category IB; Expert Opinion—Question 3).
  5. When a deceased potential organ donor's medical/behavioral history cannot be obtained or risk factors cannot be determined, the donor should be considered at increased risk for HIV, HBV and HCV infection because the donor's risk for infection is unknown (Category ID).
  6. When a deceased potential organ donor's blood specimen is hemodiluted, the donor should be considered at increased risk for HIV, HBV and HCV infection because the donor's risk for infection is unknown (Category IB; Expert Opinion—Question 3)

Testing of living and deceased donors

  1. All living potential donors should be tested for HIV, HBV and HCV as close as possible to the date of the organ recovery operation, but at least within the 28-day time period prior to surgery (Category ID).
  2. All potential organ donors (living or deceased) should be tested for antibodies to HIV (i.e. anti-HIV 1/2 or HIV antigen/antibody [Ag/Ab] combination assay). All potential organ donors identified as being at increased risk for HIV infection should also be tested for HIV RNA by NAT or HIV antigen (e.g. HIV Ag/Ab combination assay). Donor blood specimens should be obtained before procurement. Ab or Ag/Ab test results should be made available before transplantation (Category IB; Key Question 5 [Note: Optimally, all NAT results for deceased donors should be available before the transplant occurs; however, if having NAT results before transplantation is not feasible, test results can be useful to guide recipient treatment]).
  3. All potential organ donors (living or deceased) should be tested for both anti-HCV and for HCV RNA by NAT. Donor blood specimens should be obtained before procurement. Ab test results should be made available before transplantation (Category IB; Key Question 5; [Note: Optimally, all NAT results for deceased donors should be available before the transplant occurs; however, if having NAT results before transplantation is not feasible, test results can be useful to guide recipient treatment]).
  4. All potential organ donors (living or deceased) should be tested for anti-HBc and for HBsAg. Donor blood specimens should be obtained before procurement. Ag/Ab test results should be made available before transplantation (Category IB; Key Question 5).

Informed consent discussion with transplant candidates

  1. An informed consent process discussion between the transplant candidate, or medical decision maker, and the listing clinician should start before the patient is placed on the transplant wait list. Patients should be counseled to consider potential risks of both accepting and rejecting organs from donors known to be infected with HBV or HCV, or donors at increased risk for HBV, HCV or HIV infection (Category IB; Expert Opinion—Question 1).
  2. The transplant candidate, or medical decision maker, should have opportunities to discuss with clinicians issues related to the associated risk of HIV, HBV or HCV transmission with organ acceptance while the patient is on the transplant wait list (Category IB; Expert Opinion—Question 1).
  3. At the time of the organ offer, if a donor is identified as being at increased risk for HIV, HBV or HCV infection, the transplant center team primarily responsible for the patient's care should include this risk information in the informed consent discussion with the transplant candidate or medical decision maker (Category IB; Expert Opinion—Question 1).
  4. If prior to transplantation or repair of a transplanted organ it is known or anticipated that stored blood vessel conduits (from a donor who is different from the donor of the primary organ being transplanted or repaired) may be used, and the donor is identified as being at increased risk for HIV, HBV or HCV infection, then the transplant center team should include this risk information in the informed consent discussion (Category IB; Expert Opinion—Question 1).
  5. When organs from HBV- or HCV-infected donors will be used, the transplant center team primarily responsible for the patient's care should have an informed consent discussion with the transplant candidate, or medical decision maker, prior to transplantation regarding the risks related to disease transmission (Category IB; Key Question 7).
  6. Transplant candidates should be informed that although all donors are screened for HIV, HBV and HCV, donor screening has limitations and no screening question or laboratory test can completely eliminate the risk for transmitting these infections (or any other infection) (Category IB; Expert Opinion—Question 1).

Testing of recipients pre- and posttransplant

  1. Pre-transplant testing of transplant candidates for HIV, HBV and HCV should be conducted when the donor (living or deceased) meets any of the following conditions: (1) identified as being at increased risk for HIV, HBV and HCV infection (Note: If the donor is only identified as being at risk for HCV infection due to hemodialysis in the preceding 12 months, then testing for HCV only is recommended); (2) screening specimens are hemodiluted; or (3) the medical/behavioral history is unavailable. When the donor meets any of the three conditions, transplant candidate testing should occur during hospital admission for the organ transplant but prior to implantation of the organ, unless the transplant candidate is known through prior testing to be infected (Category IB; Expert Opinion—Question 2).
  2. Pre-transplant testing of transplant candidates for HBV or HCV should be conducted when the donor (living or deceased) is known to be infected with HBV or HCV. Transplant candidate testing should occur during hospital admission for the organ transplant but prior to organ implantation, unless the transplant candidate is known through prior testing to be infected (Category IB; Expert Opinion—Question 2).
  3. Posttransplant HBV testing of recipients should be conducted when the donor (living or deceased) meets any of the following conditions: (1) identified as being at increased risk for HBV infection, (2) screening specimens are hemodiluted, (3) the medical/behavioral history is unavailable or (4) the donor is infected with HBV. Recipient testing should be performed sometime between one and three months posttransplant to include HBV NAT and HBsAg, and at 12 months posttransplant to include antibody to hepatitis B surface antigen (anti-HBs), anti-HBc and either HBV NAT or HBsAg (unless infection was documented pre-transplant; Category IB; Expert Opinion—Question 2).
  4. Posttransplant HIV testing of recipients should be conducted when the donor (living or deceased) meets any of the following conditions: (1) identified as being at increased risk for HIV infection, (2) screening specimens are hemodiluted or (3) the medical/behavioral history is unavailable. Recipient testing should be performed sometime between one and three months posttransplant to include HIV NAT or an HIV Ag/Ab combination assay (unless infection was documented pre-transplant). NAT or an Ag/Ab combination assay for HIV detection is important as infected recipients may remain Ab-negative due to immunosuppression (Category IB; Expert Opinion—Question 2).
  5. Posttransplant HCV testing of recipients should be conducted when the donor (living or deceased) meets any of the following conditions: (1) identified as being at increased risk for HCV infection, (2) screening specimens are hemodiluted, (3) the medical/behavioral history is unavailable or (4) the donor is infected with HCV. Recipient testing should be performed sometime between one and three months posttransplant to include HCV NAT (unless infection was documented pre-transplant). NAT is important for HCV detection as infected recipients may remain Ab-negative due to immunosuppression (Category IB; Expert Opinion—Question 2).

Collection and/or storage of donor and recipient specimens

  1. For deceased donors, the OPO should consider collecting two blood specimens, when possible, for HIV, HBV and HCV real-time testing (i.e. prior to organ recovery)—an ethylenediaminetetraacetic acid (EDTA) plasma specimen or serum specimen for serologic assays and a separate EDTA plasma specimen for NAT. Additionally, the OPO should consider collecting two blood specimens for archiving, when possible. If it is only feasible to collect one specimen, a plasma specimen collected in EDTA, rather than a serum specimen, is optimal (Category IIB; Expert Opinion—Question 3).
  2. The OPO should consider archiving blood specimens from deceased donors for at least 10 years (Category IIB; Expert Opinion—Question 3).
  3. For living donors, transplant candidates and recipients, two blood specimens should be collected when HIV, HBV or HCV testing is planned—an EDTA plasma specimen or serum specimen for serologic assays and a separate EDTA plasma specimen for NAT (Category IB; Expert Opinion—Question 3).
  4. Infusion of crystalloid and colloid solutions and transfusion of blood products can cause hemodilution and produce false-negative results for HIV, HBV and HCV testing. Therefore, the OPO should make an effort to collect a qualified (non-hemodiluted) specimen—that is, a specimen that is deemed acceptable for testing according to an appropriate hemodilution algorithm and calculation method, such as provided by the FDA [3]. Furthermore, a hemodilution calculation should be performed on archived specimens of deceased donors to facilitate interpretation of test results (Category IB; Expert Opinion—Question 3).
  5. All stored blood vessel conduits from a donor found to be infected with HIV, HBV or HCV should be quarantined immediately and not released for clinical use unless the HBV- or HCV-infected vessel conduits are needed for the initial transplant procedure in the recipient. After completing the initial transplant procedure, any remaining vessel conduits should be disposed of in accordance with hospital policy to prevent inadvertent release from quarantine and unintentional use in other patients (Category ID).

Tracking and reporting of HIV, HBV and HCV

  • 26a.
    When an OPO receives information before organ recovery that a deceased potential donor is at increased risk for or is infected with HIV, HBV or HCV, the OPO should notify (1) the OPTN, (2) the transplant centers receiving organ offers and (3) any institutions considering tissue and eye recovery (Category IB; Expert Opinion—Question 2).
  • 26b.
    The OPO should also notify the public health authorities where the potential donor is admitted, in accordance with state requirements for reporting notifiable infections, if the deceased potential donor is infected (Category IC).
  • 27a.
    When an OPO receives information after organ recovery that a deceased donor was infected with HIV, HBV or HCV, or that an organ recipient infection with HIV, HBV or HCV is suspected of being donor-derived, the OPO should notify (1) the OPTN, (2) the transplant centers that received organs and/or blood vessel conduits from the deceased donor and (3) any institutions that recovered tissues and eyes from the donor (Category IB; Expert Opinion—Question 2)
  • 27b.
    The OPO should also notify public health authorities where the organ recovery took place, in accordance with state requirements for reporting notifiable infectious diseases, if the deceased donor was infected (Category IC).
  • 28a.
    When a transplant center receives information that a recipient of an organ or blood vessel conduit from any deceased donor is newly infected with HIV, HBV or HCV posttransplant and the infection is suspected of being donor-derived, the transplant center should notify (1) the OPTN and (2) the OPO that procured the organs and any blood vessel conduits (Category IB; Expert Opinion—Question 2).
  • 28b.
    In accordance with state requirements for reporting notifiable infectious diseases, the transplant center where the transplant took place should also notify public health authorities of the recipient infection (Category IC).
  • 29a.
    When a living donor recovery center receives information before organ recovery that a living potential donor is infected with HIVor HCV, the living donor recovery center should notify the transplant center intended to receive the organ. If the organ from an HBV- or HCV infected donor is used for transplantation, the living donor recovery center should also notify the OPTN (Category IB; Expert Opinion—Question 2).
  • 29b.
    In accordance with state requirements for reporting notifiable infectious diseases, the living donor recovery center should also notify public health authorities where the potential donor lives of the potential living donor's infection (Category IC).
  • 30a.
    When a living donor recovery center receives information after organ recovery that a living donor is infected with HIV, HBV or HCV, the living donor recovery center should notify (1) the OPTN and (2) the transplant center that received an organ from the living donor. Disclosure to the OPTN and transplant center should be in accordance with state requirements (Category IB; Expert Opinion—Question 2).
  • 30b.
    In accordance with state requirements for reporting notifiable infectious diseases, the living donor recovery center should also notify public health authorities where the organ recovery took place of the living donor's infection (Category IC).
  • 31.
    When a living donor recovery center receives information after organ recovery that an organ recipient infection with HIV, HBV or HCV is suspected of being donor-derived, the living donor recovery center should notify the OPTN (Category IB; Expert Opinion—Question 2).
  • 32a.
    When a transplant center receives information that a recipient of an organ from a living donor is newly infected with HIV, HBV or HCV posttransplant and the infection is suspected of being donor-derived, the transplant center should notify (1) the OPTN and (2) the living donor recovery center that procured the organ (Category IB; Expert Opinion—Question 2).
  • 32b.
    In accordance with state requirements for reporting notifiable infectious diseases, the transplant center should also notify public health authorities where the transplant took place of the recipient's infection (Category IC).
  • 33.
    A living donor whose blood specimen is positive for HIV, HBV or HCV when tested by the living donor recovery center should be notified by the living donor recovery center of his or her infectious disease status (Category ID).
  • 34.
    OPOs should have a system in place allowing tracking between a common deceased donor and (1) recovered organs, (2) recovered associated blood vessel conduits and (3) recovered tissues and eyes to facilitate notification when a donor-derived disease transmission is suspected. This system should include accurate records of the distribution and disposition of each organ and initial distribution of associated blood vessel conduits, along with procedures to facilitate the timely notification of transplant centers and tissue and eye recovery establishments when a donor-derived disease transmission is suspected. To facilitate notification by the OPO, transplant centers should keep accurate records of all organs and associated blood vessel conduits received and the disposition of each (Category ID).

Recommendations for Further Study

  1. Top of page
  2. Abstract
  3. Executive Summary
  4. Recommendations
  5. Recommendations for Further Study
  6. Acknowledgments
  7. Disclosures
  8. References

The systematic review for this guideline revealed numerous gaps in the evidence that affected the guideline's ability to adequately address many of the key questions reviewed. Additional gaps in evidence were identified from other sources, such as comments submitted during the public comment period or in review following public comment.

The following are 20 specific areas recommended for further study. These recommendations are arranged to correspond to the order of the 10 key questions followed by the three expert opinion questions; they are not listed in priority order.

  1. Estimate the incidence and prevalence of HIV, HBV and HCV among deceased potential organ donors in the United States (Key Question 1).
  2. Collect, analyze and report national data on HIV, HBV and HCV infection transmission rates annually based on donor and recipient testing to inform policy decisions and future screening recommendations (Key Question 2).
  3. For transplant candidates who are HBV-uninfected and receive a non-hepatic organ from an HBV-infected donor who is anti-HBc positive only, evaluate transmission rates where IgM and IgG testing is performed and where various prophylaxis measures, including vaccination, are used as a way to improve knowledge of best practices to minimize transmission risk (Key Question 2).
  4. Conduct a cost-benefit and risk-benefit analysis of archiving blood specimens that are collected from transplant candidates who are not tested for HIV, HBV and HCV just before organ transplantation. Analysis should include the feasibility of maintaining specimens at −70°C or colder (the storage temperature recommended by NAT test manufacturers) and patient safety issues associated with delays in determining whether an infection is donor-derived when a recipient is newly infected posttransplant with no pre-transplant blood specimen (Key Question 2).
  5. Identify behavioral and nonbehavioral risk factors associated with increased incidence and prevalence of HIV, HBV and HCV infection specifically among the potential organ donor population, including pediatric donors. Such data could then be used to evaluate the utility of the 12-month risk period used in the donor behavioral risk assessment for indication of recent HIV, HBV and HCV infection, and whether a shorter time interval may be an equally effective indicator (Key Questions 3 and 4).
  6. Develop and implement a validated uniform donor infection risk assessment questionnaire. To determine feasibility for possible inclusion in a future questionnaire, include the number of sexual partners in the preceding 12 months and intranasal use of an illicit drug (e.g. cocaine or heroin) in the preceding 12 months as survey questions only during the validation phase of the questionnaire (Key Questions 3 and 4).
  7. Prospectively study the performance of assays for HIV, HBV and HCV in organ donors and transplant recipients (e.g. HCV NAT). Such data also could be used to enable the calculation of useful statistics including predictive values, likelihood ratios and posttest probabilities of these tests among potential organ donors (Key Question 5).
  8. Evaluate the performance of tests, such as Ag/Ab combination assays, to be used for testing living and deceased donors and transplant recipients (Key Question 5).
  9. Develop standardized algorithms for real-time discrimination of initially reactive organ donor test results (e.g. immunoassay and NAT) to distinguish between true- and false-positive results. Retesting reactive specimens can better inform the utility of assays; the prevalence of infectious disease in the potential organ donor population; and decisions by OPOs, transplant centers and transplant candidates on organ suitability and pre- and posttransplant recipient testing (Key Question 5).
  10. Assess interventions (e.g. pathogen reduction methods) to reduce or eliminate the viral burden of HIV, HBV and HCV in donors or donor organs before or after recovery, but prior to transplantation (Key Question 6).
  11. Evaluate the risk-benefit of transplanting organs from HIV-infected donors into HIV-infected transplant candidates, given the need for transplants in HIV-infected patients and improved outcomes with the availability of highly active antiretroviral therapy. However, prior to any studies, legal analysis of the National Organ Transplant Act of 1984 [20] and the U.S. Department of Health and Human Services Final Rule [21] may be required, which obligates the OPTN to adopt standards that prevent the recovery of organs from HIV-positive donors (Key Question 7).
  12. Evaluate outcomes of patients receiving HBV- or HCV-positive organs vs. patients who remain on the transplant wait list, with statistical adjustment for relevant baseline characteristics, consideration of posttransplant prophylaxis, and consideration of patient race/ethnicity. More comprehensive analyses of competing risks would help inform critical decision-making (Key Question 7).
  13. Evaluate transplant candidate outcomes if organ donors with behavioral and nonbehavioral risk factors for HIV, HBV and HCV were declined. This process may also require comparing incidence of infection among population subsets within risk factors. If these donor organs are subsequently transplanted into other transplant candidates, include recipient outcome data (Key Questions 8 and 9).
  14. Evaluate the rate of false-positive test results (e.g. immunoassay and NAT) for HIV, HBV and HCV among potential organ donors and recipients, including analysis of the results of confirmatory tests performed for any reactive test result and the percentage of cases in which donors are declined or organs are discarded due to false-positive results, stratified by organ type (Key Question 10).
  15. Identify the limits of acceptable hemodilution. Hemodilution algorithms and calculation methods are not standardized for organ donors, and the limits of acceptable hemodilution have not been validated across HIV, HBV and HCV serologic assays used for organ donors. In addition, evaluate the effect of analyte movement from the vascular compartment during and immediately following the introduction of crystalloids or colloids to the vascular system (Expert Opinion 3).
  16. To better quantify risk based on behavior in a given donor, develop and evaluate a relative or comparative risk-based quantitative process, such as a donor risk index, to allow the transplant center and patient to assess a donor based on the donor's level of risk for transmitting HIV, HBV or HCV. Because data are lacking to calculate precise quantitative values, risk assessments in this guideline are qualitative (i.e. a donor is categorized either as being at increased risk or not at increased risk [From public comment]).
  17. Conduct a risk-benefit analysis of storing blood vessel conduits from HBV- and HCV-infected donors where the vessels would be used in transplant recipients who received an organ from the infected donor. Analysis should include the number of these recipients who are in need of subsequent vascular repair, the time frame between transplant and subsequent repair, and the availability of vessels from uninfected donors and other sources (From public comment).
  18. Study the effectiveness of systems for traceability, such as electronic bar coding, to ensure blood vessel conduits are transplanted into the intended candidates or recipients, which may allow for the safe storage of hepatitis-infected grafts for later potential use (During review following public comment).
  19. Evaluate transplantation, infection and hepatic graft outcomes for transplant candidates (both HBV-positive and HBV-negative) who receive organs from HBV-positive donors (During review following public comment).
  20. Evaluate transplantation, infection and hepatic graft outcomes for transplant candidates (both HCV-positive and HCV-negative) who receive organs from HCV-positive donors (During review following public comment).

Acknowledgments

  1. Top of page
  2. Abstract
  3. Executive Summary
  4. Recommendations
  5. Recommendations for Further Study
  6. Acknowledgments
  7. Disclosures
  8. References

I.L. and C.U. received funding from the Centers for Disease Control and Prevention to support the guideline development process. I.L. was employed by the University of Pennsylvania during guideline development and by Merck during guideline revision.

Jonathan R. Treadwell, PhD, associate director, and Meredith Noble, MS, senior research analyst from the Evidence-Based Practice Center, ECRI Institute in Plymouth Meeting, Pennsylvania, coauthored the Evidence Report, Solid Organ Transplantation and the Probability of Transmitting HIV, HBV or HCV: A Systematic Review to Support an Evidence-Based Guideline.

Further input was sought to address selected topics in developing the guideline. The following individuals wrote the original drafts of the Expert Opinion summaries: Scott Halpern, MD, University of Pennsylvania Perelman School of Medicine; Michael G. Ison, MD, Northwestern University Feinberg School of Medicine; Jutta Preiksaitis, MD, University of Alberta.

The Expert Panel and Review Committee contributed to the guideline development process and provided review and feedback on the key search questions, bibliography resulting from the literature review, and draft Evidence Report. These two groups also reviewed and provided feedback on the draft guideline. The opinions of individual members of the Expert Panel or Review Committee might not be reflected in all of the recommendations, as the guideline represents the position of the U.S. Public Health Service (PHS) and is not a consensus document. Expert Panel: Bernard M. Branson, MD, Centers for Disease Control and Prevention; Lisa A. Grohskopf, MD, Centers for Disease Control and Prevention; Richard Hasz, MFS, Gift of Life Donor Program; Scott Holmberg, MD, Centers for Disease Control and Prevention; Michael G. Ison, MD, Northwestern University Feinberg School of Medicine; Jutta Preiksaitis, MD, University of Alberta; Nicola D. Thompson, PhD, Centers for Disease Control and Prevention. Review Committee: Nancy D. Bridges, MD, National Institutes of Health; Alfred DeMaria, Jr., MD, Massachusetts Department of Public Health; Richard C. Durbin, MBA, Health Resources and Services Administration; Jan Finn, MSN, Midwest Transplant Network; Jay A. Fishman, MD, Massachusetts General Hospital and Harvard Medical School; Daniel J. Lebovitz, MD, Akron Children's Hospital, MetroHealth Medical Center, and Lifebanc; Laura St. Martin, MD, Food and Drug Administration; Karen L. Tritz, MSW, Centers for Medicare & Medicaid Services; Rainer Ziermann, PhD, Roche Molecular Systems [current affiliation: Cepheid].

The PHS Guideline Revision Work Group performed an in-depth review of public comments submitted on the draft guideline recommendations, participated in revising the recommendations in consideration of public comment, and provided feedback on the full document. PHS Guideline Revision Work Group: James Berger, MS, Office of the Assistant Secretary for Health; James Bowman, MD, Health Resources and Services Administration; Nancy D. Bridges, MD, National Institutes of Health; Joanne Cono, MD, Centers for Disease Control and Prevention; Richard C. Durbin, MBA, Health Resources and Services Administration; Melissa Greenwald, MD, Food and Drug Administration; Laura St. Martin, MD, MPH, Food and Drug Administration; Ronald O. Valdiserri, MD, Office of the Assistant Secretary for Health.

Disclosures

  1. Top of page
  2. Abstract
  3. Executive Summary
  4. Recommendations
  5. Recommendations for Further Study
  6. Acknowledgments
  7. Disclosures
  8. References

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. Executive Summary
  4. Recommendations
  5. Recommendations for Further Study
  6. Acknowledgments
  7. Disclosures
  8. References
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