NAT-positive Donors Research Articles

P8.1: Kidney acceptance from HCV NAT positive donors - Improving Organ utilization in NSW, Australia.

P8.1: Kidney acceptance from HCV NAT positive donors - Improving Organ utilization in NSW, Australia.

Epidemiology of HEV Infection in Blood Donors in Southern Switzerland.

From 2014 to 2016, the number of hepatitis E virus (HEV) infections in southern Switzerland increased dramatically and suggested food as a potential infection reservoir. We evaluated the effects of food control measures introduced to limit HEV infections, assessing anti-HEV IgG and IgM rates in blood donors before and after the implementation of food control measures in 2017. From 2012 to 2013, we screened 1283, and from 2017 to 2019, we screened 1447 donors for IgG and IgM antibodies. No statistically significant differences were detected for IgG (32.8% from 2012 to 2013 vs. 31.1% from 2017 to 2019, p = 0.337) or IgM rates (2.0% from 2012 to 2013 vs. 2.8% from 2017 to 2019, p = 0.21). Rural provenience and age > 66 are predictors for positive IgG serology. A total of 5.9% of 303 donors included in both groups lost IgG positivity. We also determined nucleic acid testing (NAT) rates after the introduction of this test in 2018, comparing 49,345 donation results from southern Switzerland with those of 625,559 Swiss donor controls, and only 9 NAT-positive donors were found from 2018 to 2023. The high HEV seroprevalence in southern Switzerland may depend on different food supply chains in rural and urban areas. Local preventive measures probably have a limited impact on blood HEV risk; thus, continuous NAT testing is recommended.

420.1: Successful Transplantation From Selected SARS-CoV-2 RNA Positive Deceased Donors

Introduction: In the UK, the SARS-CoV-2 status of deceased donors is assessed by specific questionnaire and by universal Nucleic Acid Test (NAT) for SARS-CoV-2 RNA in nose and throat swabS (NTS) and endotracheal aspirateS (ETA). Initially, only asymptomatic and NAT-negative donors were accepted. Improved understanding of the relationship of SARS-CoV-2 replication to viral RNA detection as well as a more detailed testing approach have enabled consideration of NAT-positive donors. Methods: Donor information and detailed SARS-CoV-2 RNA screening results were collected in real-time. SARS-CoV-2 NAT positivity triggered repeat sampling for the clarification of significance. Laboratory-proven diagnosis of SARS-CoV-2 infection in deceased donors or recipients of solid organs in England were captured by data linkage between the organ transplant registry and the National laboratory reporting system. Recipient infection within 14 days from organ transplantation was reviewed for the possibility of donor-transmitted infection. Results: Between 1st March 2020 and 9th February 2022, 3537 potential donors were assessed in the UK. Thirty-seven tested NAT positive during donor assessment, with 17 not proceeding to donation due to the result (15) or due to other reasons (2). Of the remaining 20, the majority had a result profile indicating previous resolved infection, with detection of residual viral RNA; in the absence of evidence of previous infection some of the very weakly reactive NAT results might have been due to false positivity. Two donors had results compatible with current but resolving asymptomatic infection. Organs from these 20 donors were offered for transplantation, resulting in 57 organ transplants into 53 recipients (3 heart, 14 liver, 3 pancreas, 31 kidney). Six lungs were transplanted from donors with NAT negative ETA and whose positive NTS results were at the limit of assay detection and not repeatable upon re-sampling. No donor-transmission of virus has been identified, with good transplant outcomes achieved. Conclusion: SARS-CoV-2 RNA positivity should be verified and interpreted in conjunction with clinical, epidemiological and virological information. In an asymptomatic individual, other than a current infection, positivity could also be due to previous, resolved infection with detection of residual viral RNA; current, resolving infection; or a false-positive result. This enables consideration of organs that would otherwise be deemed unsafe for transplantation. Our preliminary results suggest that organs other than lungs can be safely transplanted, without SARS-CoV-2 transmission, from selected NAT-positive deceased donors in whom SARS-CoV-2 infection is considered either historical or non-evolving.

Heart Transplant Outcomes by Donor HCV NAT Status: Intermediate Analysis

<h3>Purpose</h3> Donor hearts are a limited resource and inclusion of non-traditional donors such as those with hepatitis C (HCV) may help to increase transplantation rates. We sought to compare post-heart transplant outcomes of patients who received hearts from either HCV NAT positive or negative donors. <h3>Methods</h3> Recipients were identified from the UNOS Registry and stratified by donor HCV NAT status. Comparisons between cohorts were assessed using standard statistical methods, survival analysis was censored at 36 months using the Kaplan-Meier method, and multivariate Cox proportional hazard regression analysis (adjusted for age, sex, diabetes, race, ischemic time, dialysis, life support, waiting time and HLA mismatch. <h3>Results</h3> 18,828 recipients were identified of which 849 and 17,979 received HCV NAT positive (HCV+) and HCV NAT negative (HCV-) donors, respectively. HCV+ recipients were older (55.2 vs 53.5, p<0.001), male (77.4% vs 73.3%, p=0.008), and Caucasian (66.1% vs 62.1%, p=0.023). HCV+ recipients also had higher incidence of pre-transplant cardiac surgery (83.3% vs 77.9%, p<0.001), life support use (20.8% vs 16.5%, p<0.001), older donors (34.2 vs 32.1y, p<0.001), longer ischemic time (p<0.001), and with worse renal function (Cr 1.5 vs 1.4, p = 0.001). Notably, there was no difference in waitlist time. Recipients of HCV- donors were more likely to have diabetes (71.1% vs 66.4%, p = 0.004) and higher waitlist status (p<0.001). There was no difference in overall mortality between the two groups with cardiovascular (27.1% vs 26.4%) or non-cardiovascular (72.9% vs 73.6%, p=0.90) death. Unadjusted analysis demonstrated HR 0.98 (CI 0.78-1.22) and following adjustment HR 0.99 (0.78-1.24). <h3>Conclusion</h3> Utilization of HCV NAT positive donor hearts presents as a safe and effective way to expand the donor pool with no survival difference in this intermediate analysis. Further study is needed to understand the long-term outcomes of this population, particularly in the setting of widely available curative therapies.

Outcomes of Lung Transplantation From Hepatitis C Viremic Donors

BackgroundDirect-acting antiviral (DAA) therapy for hepatitis C virus (HCV) has encouraged lung transplantation with HCV positive donors. Early trials have been promising; however, nationwide data have not been previously examined. MethodsThe United Network for Organ Sharing registry was queried for adult patients receiving lung transplants from 2016 to 2019. We excluded multiorgan transplants, incomplete data, and loss to follow-up. Nucleic acid testing (NAT) determined HCV status. Propensity matching was performed for comparison of outcomes. ResultsHepatitis C virus NAT-positive lungs were transplanted in 189 patients, compared with 9511 recipients of NAT-negative lungs. The HCV NAT-positive donors were younger (mean 33 vs 35 years, P = .017) with higher rates of Pao2/Fio2 greater than 300 (83.6% vs 76.5%, P = .029). Recipients of NAT-positive lungs had lower lung allocation scores (mean 39.3 vs 42.4, P = .009). Distance traveled was significantly further for HCV viremic donor lungs (mean 416 vs 206 miles, P < .001). Kaplan-Meier survival analysis demonstrated no difference in survival (P = .56). There were no differences in airway dehiscence (P = .629), acute rejection (P > .999), or reintubation (P = .304). At mean follow-up of 395 days, 63 recipients of NAT-positive lungs (40%) seroconverted, 14 with viremia. One-year mortality rates among seroconverted patients was 6% and did not differ significantly from 14% in nonseroconverted patients or 13.2% in recipients of HCV-negative lungs. ConclusionsShort-term outcomes of lung transplantation from HCV viremic donors are promising, with no difference in early complications or survival. The effects of seroconversion and long-term outcomes including chronic rejection and infection need to be further explored.

Donor Characteristics and Regional Differences in the Utilization of HCV-Positive Donors in Liver Transplantation

Increased utilization of hepatitis C virus (HCV)-positive liver allografts for liver transplant (LT) has been endorsed as one of several ways to combat national organ shortages. However, HCV-positive donors remain poorly characterized, and Organ Procurement and Transplantation Network regional differences in the utilization of HCV-positive liver allografts are unclear. To characterize HCV-positive donors and the allografts that come from them. In this cross-sectional study, the Scientific Registry of Transplant Recipients database was queried for all donors who underwent HCV testing from June 2015 to December 2018. Clinical and allograft characteristics were evaluated, and utilization across the United States was studied. Patients with positive or negative results for HCV antibody (Ab) and HCV nucleic acid amplification testing (NAT) were included in this study. Donors utilized for living donor transplant and pediatric (age <18 years) recipients were excluded. The primary comparison was between donors who were HCV Ab positive and those who were HCV Ab negative. Regional variations in the utilization of HCV-positive and HCV-negative donors were analyzed. Of 24 500 donors utilized for LT, 1887 (7.7%) were HCV Ab positive; 64.4% of HCV Ab-positive donors were HCV NAT positive. HCV Ab-positive donors were younger (median [interquartile range] age, 35 [29-46] years vs 40 [27-54] years) and had fewer comorbidities, such as diabetes (8.3% vs 12.0%) and hypertension (25.9% vs 35.2%), compared with HCV Ab-negative donors. These findings were even more pronounced in HCV Ab-positive /NAT-positive compared with HCV Ab-positive/NAT-negative donors. Organ Procurement and Transplantation Network regions 2, 3, 10, and 11 had the highest absolute utilization of HCV Ab-positive donors, accounting for 64.4% of all HCV Ab-positive donors used in the United States. Region 1 had the highest relative utilization of HCV Ab-positive donors (18.7%). The use of HCV Ab-positive donors in some regions was associated with the rate of drug overdose, but this was not always the case. Similar utilization results were found with HCV NAT-positive donors. In this cross-sectional study, HCV-positive donors were younger and healthier than utilized HCV-negative donors. Significant differences exist in the utilization of HCV-positive donors across the 11 Organ Procurement and Transplantation Network regions, which is not entirely explained by organ demand or by higher availability of HCV-positive livers as per the distribution of the opioid epidemic. Initiatives to increase the use of HCV-positive donors, particularly in regions of high organ demand, should be implemented.

Donor Derived Cell Free DNA in Recipients of Hepatitis C Viremic Donors as a Possible Marker of a Pro-Inflammatory State Causing Graft Injury

Since the highly effective Direct-Acting Antiviral (DAA) therapies have been available for treatment of HCV, transplant centers have begun using organs from HCV infected donors followed by treatment with DAAs. Epidemiological studies have shown that HCV may be associated with an increase atherosclerosis and it has been hypothesized that this is caused by activation of an immunological or inflammatory response. HCV infection of endothelial cells may promote endothelial dysfunction and early atherogenesis. The question arises, could acute HCV that is treated expeditiously, cause an inflammatory response leading to rejection or CAV in the heart transplant population. We plan to compare all recipients at our institution enrolled in the Surveillance HeartCare Outcomes Registry (S.H.O.R.E.) for increased donor derived cell free DNA (dd-cf DNA). They will be placed in 3 population categories: 1) Recipients of Non HCV donors, 2)Recipients of NAT positive donors and 3) Recipients of Antibody positive, NAT negative donors. After solid organ transplantation, donor-derived cell-free DNA circulates in the recipient's blood, and accounts for only a small fraction of total cfDNA (recipient plus donor-derived). During graft injury high amounts of donor-derived cell-free DNA (dd-cfDNA) are shed into the blood stream. HeartCare assesses heart health by measuring both immune activity and dd-cfDNA. The recommended threshold for Cell injury is greater than 0.2 % dd-cf DNA. We will compare populations by episodes of rejection, type of rejection and CAV at one year. At our institution there are currently 6 recipients of donor hearts that were HCV NAT positive and 3 recipients of HCV antibody positive but NAT negative. Participants will receive HeartCare at routinely scheduled intervals of every other month starting at month 4 for the first year and then quarterly out to 5 years post-transplant. We will compare populations by episodes of rejection, type of rejection and CAV at one year.

Use of Donor HCV NAT Positive Hearts: Expanding the Donor Pool?

Purpose Use of HCV NAT+ donor hearts may aid in expanding the donor pool. However, limited single center data exist. We aim to assess the short-term impact of use of HCV NAT+ hearts in a national dataset. Methods 8256 HT patients with reported donor HCV NAT status were identified from UNOS (2010-2018), of which 88 received an HCV NAT positive (HCV+) donor. Exclusions included age proportional hazard regression analysis (adjusted for age, sex, diabetes , race, ischemic time , dialysis, life support & HLA mismatch) was performed. Results 88 pts underwent successful HT with HCV NAT positive donors. Predominant etiologies did not differ (p=0.169). During study period, 826 pts died post HT (NAT + vs -: 9.1 vs 10.0, p=0.77). Crude 1, 6 & 12 m post-HT survival was NAT+ [96, 91, 82%] vs NAT- [97, 93, 91%] (log-rank, p Multivariate analysis yielded a hazard ratio of 1.45 (CI 0.65-3.28) comparing NAT+ to NAT- recipients. Conclusion Short-term survival is similar between HCV NAT+ versus NAT- HT recipients. This data is promising and represents a step forward in expanding the donor pool. Further study is warranted to assess the long-term impact of this donor population.

Hepatitis C virus (HCV) RNA level in plasma and kidney tissue in HCV antibody-positive donors: Quantitative comparison.

Kidney transplant from donors with hepatitis C virus (HCV) antibody has been limited to HCV viremic recipients only, due to concern of the HCV transmission. However, the new antiviral medications provide an opportunity to expand the utilization of these donors. To study the risk of HCV transmission in kidney transplantation, we used discarded donor kidneys and determined HCV RNA levels by quantitative real-time PCR in bilateral (right and left) kidney biopsies and plasma from 14 HCV antibody-positive donors (sensitivity: 15 international unit (IU)/mL plasma; 1.8IU/50nL kidney). In three NAT-negative donors, HCV RNA was negative in plasma and kidney. In all 11 NAT-positive donors, HCV RNA was positive in plasma (range: 5807-19134177IU/mL) but negative in six kidneys from four donors with plasma HCV RNA <1.5million IU/μL. HCV RNA correlated between right and left kidneys (P=0.75) and between kidney and plasma (r=0.86). When normalized by volume, HCV RNA median (range) was 49 (0-957) IU/50nL plasma and 1.0 (0-103) IU/50nL kidney, significantly lower in kidney (P=0.005) than in plasma (14-fold). Plasma HCV RNA can be used to predict the kidney HCV load. Future studies are needed if plasma/kidney HCV levels can be used to stratify donors for transmission risk and recipients for post-transplant management in extended utilization of HCV antibody-positive donors.

Deceased organ donor screening for human immunodeficiency virus, hepatitis B virus and hepatitis C virus: Discordant serology and nucleic acid testing results.

Before the 2014 policy change pertaining to infectious disease screening, many organ procurement organizations (OPOs) were supplementing serologic screening of deceased organ donors with nucleic acid testing (NAT) for human immunodeficiency virus (HIV-1), hepatitis B virus (HBV), and hepatitis C virus (HCV). The number of seronegative, NAT-positive donors has not been directly measured. HIV, HBV, and HCV screening results of 11229 donor referrals evaluated from 2010 to 2013 were obtained from 3 OPO-affiliated laboratories, capturing 35% of all donors in the United States. Laboratories used either polymerase chain reaction assay or transcription-mediated amplification assay to test 9643 deceased donors by NAT. The NAT results were positive in 21 (0.2%), 1 (0.02%), and 11 (0.1%) donors who were seronegative for HIV, HBV, and HCV, respectively. All discordant HIV-1 results were from one laboratory using a polymrease chain reaction assay. Thirteen of the reactive HIV NAT results in seronegative referrals were repeated and were non-reproducibly positive (NRP). Ten (0.1%), 452 (7.8%), and 197 (2.2%) of HIV-, HBV-, and HCV-seropositive donors, respectively, were negative by NAT. This study highlights the importance of robust quality assurance to minimize NRP NAT results. NAT may allow for increased utilization of organs from HBV- and HCV-seropositive, NAT-negative donors.

Utilization of Organs From Donors According to Hepatitis C Antibody and Nucleic Acid Testing Status: Time for Change.

Previous studies have grouped all donors positive for hepatitis C virus (HCV) antibody (Ab). Only recently has donor HCV nucleic acid testing (NAT) become routine, and the impact of Ab and NAT status on organ utilization is unknown. Using the United Network for Organ Sharing database, we identified 9290 donors from 2015 to 2016 for whom both HCV Ab and NAT data were available and compared organ utilization by HCV status. Overall, 93.8% of donors were Ab negative and NAT negative (Ab-NAT-), 0.15% were Ab negative and NAT positive, 1.8% were Ab positive and NAT negative (Ab+NAT-), and 4.2% were both Ab and NAT positive (Ab+NAT+). Ab-NAT- donors donated at the highest rate for all organs except livers, of which Ab+NAT- donors donated at a higher rate (81.2% vs 73.2%, p=0.03). Livers were discarded for reasons related to abnormal biopsies in Ab+NAT+ donors, whereas kidneys from Ab- or NAT-positive donors were discarded for reasons related to HCV status. Using a propensity score-matched model, we estimated that using Ab+NAT- donors at the same rate as Ab-NAT- donors could result in 48 more kidney donors, 37 more heart donors, and 15 more lung donors annually. We urge the use of HCV Ab+NAT- donors for appropriately selected and consenting recipients.

NAT positivity in seronegative voluntary blood donors from western India

Background and objectivesPrevalence and composition of Hepatitis B, Hepatitis C and HIV-1, NAT positive but seronegative voluntary blood donors from western part of India is yet to be documented. Material and methodsOver last 2 1/2 years all the seronegative voluntary blood donors were tested using 10 minipools on a semiautomated NAT testing platform. The positively tested donors were followed up for at least five months for development of seropositivity. Results79532 seronegative donations were tested by 10 minipool (MP) NAT leading to 51 positive sample (44 Hep B, 5 HIV 1 and Hep C positive). All the HIV and Hep C NAT positive donors eventually developed seropositivity and out of 44 Hep B NAT positive donors, 31 developed seropositivity within six months of follow up, following counseling of the donors. This data translate into NAT yield of 1:1559 donors for all virus taken together. NAT yield for Hep B 1:1807 donors were much higher than HIV 1 in 1:15906 and HCV yield of 1:39761. Semiautomated minipool NAT testing system was found to be cost effective way for improving blood safety. Interpretation and conclusionSeronegative NAT yield in voluntary blood donors are quiet high in western part of India and in line with rest of the country is mainly due to Hepatitis B infection. Implementation of strict donor screening, Hep B vaccination of the population and sample mutation of NAT testing should be under taken on war footing.

Prevalence and trends of markers of hepatitis B virus, hepatitis C virus and human Immunodeficiency virus in Argentine blood donors.

BackgroundTransfusion-transmitted infections are a major problem associated with blood transfusion. The aim of this study was to determine prevalence and trends of HBV, HCV and HIV in blood donors in Argentina.MethodsA retrospective study was carried out in blood donors of 27 transfusion centers covering the whole country over a period of eight years (2004-2011). Serologic screening assays for HBsAg, anti-HBc, anti-HCV, and anti-HIV were performed in all centers and nucleic acid amplification testing (NAT) was performed in 2 out of the 27 centers.ResultsThe 2,595,852 samples tested nationwide from 2004 to 2011 showed that the prevalence of HBsAg decreased from 0.336% to 0.198% (p < 0.0001), that of anti-HBc from 2.391% to 2.007% (p < 0.0001), that of anti-HCV from 0.721% to 0.460%, (p < 0.0001) and that of anti-HIV from 0.208% to 0.200 (p = 0.075). The prevalence of HBV, HCV and HIV was unevenly distributed among the different regions of the country. Two out of 74,838 screening- negative samples were positive in NAT assays (1 HIV-RNA and 1 HCV-RNA); moreover, HBV-DNA, HCV-RNA and HIV-RNA were detected in 60.29, 24.54 and 66.67% of screening-positive samples of the corresponding assays. As regards donors age, positive HBV-DNA and HCV-RNA donors were significantly older than healthy donors (46.6, 50.5 and 39.5 y respectively, p < 0.001).ConclusionsArgentina has a low prevalence of HBsAg, anti-HCV and anti-HIV in blood donors, with a decreasing trend for HBsAg, anti-HBc and anti-HCV but not for anti-HIV over the last 8 years. The uneven distribution of transfusion-transmitted infections prevalence among the different regions of the country highlights the need to implement regional awareness campaigns and prevention. The discrepancy between samples testing positive for screening assays and negative for NAT assays highlights the problem of blood donors who test repeatedly reactive in screening assays but are not confirmed as positive upon further testing. The uneven distribution of age between healthy donors and NAT-positive donors could be related to changes in risks of these pathogens in the general population and might be attributed to a longer exposure to transmission risk factors in elderly people.

Incidence of HCV and HIV NAT Positive in Cord Blood Donors.

Introduction:Donors of cord blood (CBD) are screened similarly to whole blood donors (WBD). It has been reported that CBD have a higher incidence of both true positive and false positive disease markers tested by EIA[1]. This abstract compares the rate of positive results for viral RNA (NAT) in CBD vs. WBD in a large cohort of donors.Methods:NAT was performed using the Chiron Procleix MPX or discriminatory assays. EIA testing was performed using Abbott bead methodology following manufacturer's instructions. Confirmatory results for EIA were performed with Chiron RIBA. Results from 12/17/04 to 6/30/05 were collated.ResultsEIA HIVEIA HCVNAT HIV/HCVHIV EIA POS(%)HCV EIA POS (%)HIV NAT POSHCV NAT POSWBD74299742997429975(0.10)107(0.14)1 (0)31(0.04)CBD11996120011200750(0.42)46(0.38)013 (0.11)A higher percentage of CBD were positive for HIV and HCV EIA as previously reported1. HIV NAT positive donors were 0.00% for both populations. The ratio of HCV EIA positive to HCV NAT positive donors was 28.97% for WBD and 28.26% in CBD. The ratio of CBD HCV EIA positives to WBD HCV EIA positives is 2.71 and the ratio of WBD HCV NAT positives to WBD HCV NAT positives is 2.75. The ratio of HIV CBD EIA positives to HIV WBD EIA positives is 4.10, which is significantly higher (p=<0.01).ConclusionsBoth CBD and WBD have a low rate (0%) of HIV NAT positive donors, but CBD have a 4x higher rate of HIV EIA. This suggests a 4x higher donor loss to false positive antibody results. The CBD donors have a 2.7x higher rate for both EIA and NAT positive results, showing a higher rate of viremic donors in CBD. The similar ratios for EIA positive to NAT positive donors in the two populations suggest that the false positive rate is not elevated in CBD versus WBD.The higher incidence of HCV infection in CBD could be geographic or ethnic in origin. More study is needed to determine the reasons and further predict donor loss. The HIV EIA results are not predictive of actual infection in this population. A more aggressive logarithm for reentry than used for WBD may be merited.

Epidemiology of blood donors in Japan, positive for hepatitis B virus and hepatitis C virus by nucleic acid amplification testing

The Japanese Red Cross screens seronegative blood donors by nucleic acid amplification testing (NAT) for hepatitis B, hepatitis C and human immunodeficiency virus-1 markers. NAT-positive donors thus identified seemed to have a different infectious background from serologically positive donors. The purpose of our study was to characterize this background in the hepatitis B virus (HBV) and hepatitis C virus (HCV) NAT-positive donors. Some 328 HBV DNA-positive and 44 HCV RNA-positive donors were detected by NAT testing of seronegative blood donors. These were characterized regarding age, gender and genotype of HBV and HCV. Those who were HBV NAT-positive were mainly young, in particular teenage girls. In Japan, genotypes C and B have previously been dominant, but recently genotype A has increased, and genotype H was recently detected. In HBV NAT-positive donors, the rate of genotype A was high (12.2%) compared with patients in hospital (1.7-2%). Donors who were HCV NAT-positive were also young, but mostly men in their twenties. The ratio of genotype 1b to 2a or 1b to 2b in HCV NAT-positive donors differed from that of hospitalized patients in Japan. We did not find genotype 1a, which is dominant in the USA. The high-risk donors detected by NAT were mainly young, with a different distribution of genotypes from that of hospitalized patients, regarding both HBV and HCV. The rare HBV genotype H has been found for the first time in Japan. The findings reflect the present spread of hepatitis viruses B and C.