Guidance on the Use of Increased Infectious Risk Donors for Organ Transplantation

Some deceased potential organ donors are identified as being at increased risk for specific infectious pathogens based on donor demographic and behavioral characteristics. Despite negative serology testing, these donors may be at risk for transmitting certain pathogens, especially human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B virus (HBV), because of window period (WP) infections (1, 2). These donors may be classified as “high-risk donors” or as “increased risk donors” (IRDs). The Canadian Cells, Tissues, and Organ Regulations are based on the National Standard. The Canadian Standards Association (CSA) General Standard CAN/CSA Z900.1 includes exclusion criteria based on behavioral risk factors. These have recently been updated and are shown in Table 1. Organs from these donors may be used through a process known as “exceptional distribution” (Canadian Cells, Tissues, and Organ Regulations [available at http://laws-lois.justice.gc.ca/eng/regulations/SOR-2007-118/FullText.html] address the process of “Exceptional Distribution” in Sections 40 to 42). Given the significant discrepancy between donor organ supply and demand, coupled with low organ donation rates in certain Canadian jurisdictions and high recipient wait-list mortality (Table 2), many of these donor organs are used. However, significant discrepancies in utilization practices have been documented within other countries (3, 4). Such heterogeneity in utilization practices likely exists in Canada; however, published Canadian data are lacking.TABLE 1: Summary of 2012 CSA increased-risk donor criteriaTABLE 2: Estimated Canadian wait list numbers and mortalityaTo provide guidance to the transplant community, the Canadian Society of Transplantation together with the Canadian National Transplant Research Program have developed a framework to provide guidance for deceased donor utilization of these IRDs in Canada. Guidance Development Process A conference was held in March 2013 to develop Canadian recommendations for using deceased donors with behavioral risk factors for HIV, HCV, and HBV. Conference participants included experts from Canada in organ and tissue donation and transplantation, transplant infectious diseases, laboratory medicine, and epidemiology. Additional content expertise was provided by Health Canada, several major Canadian Organ Procurement Organizations, and Canadian Blood Services. Before the conference, separate working groups were formed to address issues related to behavioral risk factors, modeling and residual risk analysis, informed consent process, and posttransplant recipient testing. Each group distributed a report to all participants before the meeting. At the conference, the working group findings were discussed in detail, and all participants developed recommendations by consensus. Where applicable, the recommendation was categorized according to the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system based on strength of recommendation (strong, weak) and quality of evidence (high, moderate, low, or very-low) (www.gradeworkinggroup.org). Behavioral Risk Assessment of Donors All participants agreed that the term “high-risk” donor may be misleading because organ transplantation is associated with much more common, recognized risks including wait-list mortality, surgical complications, and complications related to posttransplant immunosuppression (5). The term “increased risk” (in donors with identified risk factors for these infections) was agreed on. Behavioral risk factors for HIV, HCV, and HBV are assessed by history and physical examination of the donor. In 2012, the CSA updated the behavioral risk criteria for use by Canadian Organ Procurement Organizations (6). These are summarized in Table 1. In addition, the U.S. Public Health Service (PHS) has published updated criteria for behavioral risk assessment (7). The PHS guidelines use similar criteria to the CSA except for the inclusion in the PHS guidance of the following as increased risks: (1) persons who have been newly diagnosed with or treated in the last 12 months for syphilis, gonorrhea, chlamydia, or genital ulcers; and (2) hemodialysis in the last 12 months (HCV risk only). In addition, in the PHS criteria, 12 months is used as the timing for all risk factors (as opposed to 5 years). Also, the PHS criteria do not include nonsterile tattooing or piercings as a risk factor. Of note, hemophilia as a risk factor has been removed from both guidelines (6, 7). Mathematical Modeling of Residual Risk Possibly, the most important aspect in the risk versus benefit analysis that is undertaken when organs from IRDs become available is the potential risk for transmission of an infectious agent. Residual risk estimates have been published based primarily on U.S. epidemiologic data (8, 9). To determine the risk in a Canadian population, we performed a systematic review of incidence and prevalence studies as outlined below and in Appendix S1 (SDC,https://links.lww.com/TP/B14). It should be emphasized that the risk modeling is not based on studies of actual organ donors but on incidence and prevalence studies in specific high-risk categories. Modeling was focused on HIV and HCV because insufficient data were available for HBV, especially in the era of significant vaccine utilization in Canada. Systematic Review Detailed methodology and results of the systemic review are presented in Appendix S1 (SDC,https://links.lww.com/TP/B14) and summarized below in Tables 3 and 4 (10–37). In brief, we identified 5,731 abstracts through a search of PubMed and reference mining; 391 were eligible for inclusion in the full-text screening, and 66 reported the incidence or prevalence of HIV or HCV in a Canadian population between 1995 and 2012 (Appendix S1, Figure S1, SDC,https://links.lww.com/TP/B14). From those, we abstracted 62 unique estimates among populations meeting the criteria for one of the seven IRD categories. In addition, a recent review of 25 studies was used to estimate the risk of a WP infection from exposure to HIV-infected blood. Estimates of residual risk are provided per 10,000 donors if enzyme-linked immunosorbent assay or NAT are used for screening. In addition, the estimate is converted to a ratio to provide a number that can be more easily conveyed to patients during the informed consent process. However, it should be emphasized that these risk estimates are derived not from organ donors, but from living persons in whom behavioral risk is known. The actual risk in deceased donors may be lower and will depend on additional factors, such as likelihood of recent high-risk behavior, and length of hospitalization before donation with risk generally decreasing as duration of hospitalization increases.TABLE 3: Risk per 10,000 donors of an HIV infection occurring during the window period, by ELISA and NAT. Assumes a WP of 21 days for ELISA and 7 days for NATTABLE 4: Risk per 10,000 donors of an HCV infection occurring during the window period, by ELISA and NATRecommendations for Utilization of Increased Risk Deceased Donors Increased utilization of organs from IRDs in a safe and ethical manner may lead to an increase in number of transplants in Canada coupled with decreased wait-list times and mortality. Risk exists for all donors and includes the (undefined) risk of false-negative testing (both serology and NAT). Based on a review of residual risk assessments as well as Canadian wait list mortality data, the following recommendations were agreed on by group consensus: Transplant physicians and surgeons should consider the utilization of organs from IRDs. This should be performed in conjunction with NAT testing for HCV and HIV, and hepatitis B surface antigen or NAT for HBV. Some development work is required to ensure that NAT is available across all jurisdictions in Canada (strong recommendation, moderate quality evidence). All potential recipients should be made aware of the option to consider accepting organs from IRDs and that declining such an offer will not impact their waiting time for a standard risk (non-IRD) organ. Appropriate informed consent from potential recipients should be obtained. It is suggested that a standardized informed consent process be used (see informed consent section; a potential standardized informed consent template is provided in Table 5). A recommendation was made that information also be provided in an elective manner at the time each potential recipient has consented to be placed on an organ donor wait list.TABLE 5: A potential template for standardized informed consent script that can be read to the patient at the time of offer Decisions around utilization or nonutilization may take into account the timing of increased risk behavior, the WP for the specific test used, and the status of the recipient as well as other recipient-specific circumstances. Recipients of organs from IRDs should undergo follow-up posttransplant testing for HCV, HIV, and HBV. NAT for HIV and HCV is necessary because transplant patients may not seroconvert (1). A recommended algorithm is provided in Table 6 (strong recommendation, low-quality evidence). TABLE 6: A potential testing algorithm for posttransplant assessment of recipients of organs from increased risk donorsInformed Consent for Potential Recipients of Increased Risk Deceased Donor Organs Adequate informed consent for potential recipients of organs from IRDs is essential. Contextualizing the risk in a clear and understandable perspective is important. The information provided to patients should be accurate and nonleading. Risk estimates from Tables 3 and 4 are based on Canadian data and may provide useful guidance when explaining risk to potential recipients. The following are important aspects of the informed consent process: The discussion should be at the time of listing and again at the time of offer. The discussion should take place with the physician although other members of the team may also be involved. Although a patient may decline this option at the time of listing, this could be reassessed throughout the waiting period and the time of offer because clinical and other circumstances may change. A standardized informed consent process is useful, and a recommended template is provided. This may be modified as needed for center-specific practices. A separate standardized informed consent template may be needed for kidney versus non-kidney recipients given the availability of dialysis for support of end-stage renal failure patients. There is evidence to suggest that centers using a standardized informed consent process have higher utilization of organs from IRDs (38) (strong recommendation, moderate quality evidence). Documentation of the informed consent process is essential. Institutional requirements may vary as to the format of documentation in the medical record and should be followed. Follow-up Testing Recommendations for Recipients If organs from IRDs are used, posttransplant testing of recipients is recommended for early detection of potential transmissions (strong recommendation, low-quality evidence). Because delayed seroconversion may occur, posttransplant screening with NAT for HIV and HCV is recommended along with NAT or hepatitis B surface antigen testing for HBV (1). A potential proposed algorithm for testing is shown in Table 6. Other testing algorithms may also be reasonable (see PHS guidelines, reference 7) but should include NAT for HIV and HCV. Future Recommendations A central database for collection of data related to used and non-used deceased organ donors would provide valuable information and is currently planned as part of the Canadian National Transplant Research Program. This should be tied to recipient data including clinical and laboratory outcomes and documentation of transmission events. In addition, uniform availability of NAT testing across Canada is an important issue that needs to be addressed because this may limit the ability of some Canadian centers to use organs from IRDs. Ultimately, a Canadian registry of wait-listed patients, who would be willing to consider an offer from more risk donor, may assist with efforts to optimize utilization. Summary Optimal utilization of deceased donor organs from IRDs should be performed in a safe and ethical manner. This includes appropriate testing of donors and rigorous informed consent of potential recipients. Transplant programs may consider discussing their protocols with hospital senior leadership before finalizing policy. Overall, a more standardized approach across Canada should lead to optimized utilization practices and a significant increase in the number of organ transplants.