Is Nucleic Acid Testing for Organ Donors the ‘Right’ Choice? Reference: Humara A, Morrisb M, Blumbergc R, et al. Nucleic acid testing (NAT) of organ donors: Is the ‘best’ test the right test? A consensus conference report. Am J Transplant. 2010;10:889–899.

Introduction Nucleic acid testing (NAT) is considered important for HIV, HBV and HCV in screening potential organ donors. Nucleic acid testing reduces the risk of death while awaiting transplantation, as this reduces the time needed for donor screening tests. Thus, NAT is different from screening blood or tissue donors. Infections like HIV, HCV and HBV can be reduced through NAT. In a case seen in 2007, the transplant recipient was transmitted with HIV and HCV; and serology testing was negative but subsequent analysis with NAT, detected the presence of viremia, suggesting a false-negative serology or a true window period infection due to hemodilution. The NAT cannot be recommended as universal prospective screening due to insufficient evidence. Reduction in the risk of disease transmission without the loss of donor is based on further viral screening studies.

Consensus Development Process A consensus conference was conducted and participated by authorities from the US and Canada in the fields of organ and tissue donation and transplantation, transplant infectious diseases, blood banking, laboratory medicine and epidemiology. Discussion related to practical development for using NAT in the screening of potential organ donors for HIV, HCV and HBV was held. The developed proposals of the participants were discussed in detail and possible level of evidence was provided to these proposals.

Current NAT Practices A survey was held in 2008 by organ procurement organizations (OPOs), which recognized that 47% performed NAT on all potential donors, and another 28% performed NAT on subset donors. Organ donors are also tissue donors. Tissue donors routinely undergo NAT for HIV-1 and HCV, which is performed by tissue banks.

Organ Donation vs. Blood- and Tissue-Donation The NAT in organ transplant differs from tissue transplant in risks and benefits. Existing practices in blood- and tissuedonation cannot be applied in screening organ donors, since time is a crucial factor for organ donation. Delay in recovery of organ and functioning, may lead to many infections due to susceptibility. The urgency, geography and other logistical issues should be considered for potential organ donors during testing.

NAT Risk: Benefit Analysis To analyze the improvements in disease transmission, NAT should be weighed against the risk of disposal the organs from donors with false-positive results. Reliable data on infection rates in potential organ donors are not available but it is seen that prevalence rates are higher than the reports in potential blood donors owing to the demographics of the donor population and failure to obtain a medical assessment from the deceased donor (see Table 1).

Behavioral Risk Assessment of Donors Factors for behavioral risk are assessed by the history and physical examination of the donor. Limited information can be known from the families of increased risk donors. The criteria for defining the high-risk donor are shown in Table 2.

Estimating NAT Yield in Increased-Risk Donors Published prevalence data on various behavioral risks, incidence window-period (I-WP) modeling was used to estimate the chances of a missed window period of HIV, HCV or HBV infection utilizing standard serology. The I-WP model predicts that NAT decreases the residual risk of infection to a higher level in increased- risk donors when compared to average risk donors when added to a screening test with comparatively long vs. a short window period (see Fig. 1). Figure 1 shows residual risk estimation with serology vs. NAT for specific incidence groups, which is based on the incidence data from several studies.

NAT Recommendations For Deceased Organ Donors Nucleic acid testing is considered, as it reduces the risk of disease transmission and helps in organ utilization in increased risk donors. The highest risk in such cases is HCV infection. Nucleic acid testing cannot be recommended on a routine basis for HIV, HCV and HBV due to insufficient evidence for screening all potential donors.

NAT Recommendations For Living Donors Information about their behavior is accurate and hence routine NAT for HIV, HBV and HCV is not compulsory among average risk donors. Nucleic acid testing can be considered when organ donation time approaches. Repeat in serological tests after window period infection in increased-risk living donors is suggested.

NAT Recommendations Laboratories Performing NAT Establishment of standards in testing laboratories. Advancement in standardized approaches of specimen labeling and transportation. Implementation of standardized algorithms for realtime discrimination of initially reactive NAT results.

Tests for HIV, HCV and HBV should be done at periodic intervals when the recipients receive organs from increased risk donors. Organ candidates should be informed of the risk factors like donor-transmitted infection. Limitation of testing should be informed as tests for each pathogen cannot be considered. Information about donor history should be discussed with the recipient to enable the recipient to understand the risk. Kinds of tests performed should be explained. Further studies are required in considering the efficacy and feasibility of NAT in organ donors.

Summary Critical infections like HIV, HBV and HCV, and the risk of accidental diseases transmission can be reduced through screening of donor organs. Increased sensitivity of NAT and their routine use may lead to loss of transplantable organs due to false-positive results. Best results can be predicted by weighing the benefits and risks of NAT in the overall situation of donor testing, organ utilization, and prevention of wait-list morbidity and mortality.