Impact of US Public Health Service increased risk deceased donor designation on organ utilization

Under US Public Health Service guidelines, organ donors with risk factors for human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) are categorized as increased risk donors (IRD). Previous studies have suggested that IRD organs are utilized at lower rates than organs from standard risk donors (SRD), but these studies were conducted prior to universal donor nucleic acid test screening. We conducted risk‐adjusted analyses to determine the effect of IRD designation on organ utilization using 2010‐2017 data (21 626 heart, 101 160 kidney, 52 714 liver, and 16 219 lung recipients in the United States) from the Organ Procurement and Transplantation Network. There was no significant difference (P < .05) between risk‐adjusted utilization rates for IRD vs SRD organs for adult hearts and livers and pediatric kidneys, livers, and lungs. Significantly lower utilization was found among IRD adult kidneys, lungs, and pediatric hearts. Analysis of the proportion of transplanted organs recovered from IRD by facility suggests that a subset of facilities contribute to the underutilization of adult IRD kidneys. Along with revised criteria and nomenclature to identify donors with HIV, HBV, or HCV risk factors, educational efforts to standardize informed consent discussions might improve organ utilization.     

Hepatitis B and C virus infections transmitted through organ transplantation investigated by CDC,United States, 2014‐2017

We evaluated clinical outcomes among organ recipients with donor‐derived hepatitis B virus (HBV) or hepatitis C virus (HCV) infections investigated by CDC from 2014 to 2017 in the United States. We characterized new HBV infections in organ recipients if donors tested negative for total anti‐HBc, HBsAg and HBV DNA, and new recipient HCV infections if donors tested negative for anti‐HCV and HCV RNA. Donor risk behaviors were abstracted from next‐of‐kin interviews and medical records. During 2014‐2017, seven new recipient HBV infections associated with seven donors were identified; six (86%) recipients survived. At last follow‐up, all survivors had functioning grafts and five (83%) had started antiviral therapy. Twenty new recipient HCV infections associated with nine donors were identified; 19 (95%) recipients survived. At last follow‐up, 18 (95%) survivors had functioning grafts and 14 (74%) had started antiviral treatment. Combining donor next‐of kin interviews and medical records, 11/16 (69%) donors had evidence of injection drug use and all met Public Health Service increased risk donor (IRD) criteria. IRD designation led to early diagnosis of recipient infection, and prompt implementation of therapy, likely reducing the risk of graft failure, liver disease, and death.     

Organ transplantation from “increased infectious risk donors”: the experience of the Nord Italia Transplant program — A retrospective study

The purpose of this study was to assess the safety and the clinical outcome associated with organ transplantation from increased infectious risk donors (IRD). We retrospectively identified all adult deceased IRD referred to the Nord Italia Transplant program coordinating center from November 2006 to November 2011. All potential donors were screened for social risk factors that may increase the risk of donor‐derived infection with human immunodeficiency (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV). All recipients were followed monthly for the first 6 months post‐transplant. A total of 86 potential IRD were identified during the study period. Three hundred and seventy‐nine organs from IRD were offered to the transplant centers, but only 185 (48.8%) were used for transplantation. Organs from IRD were transplanted into 174 recipients. The complete follow‐up data were available for 152 of 174 (87.3%) recipients. During a mean follow‐up of 11.7 months (median 12; range 2.4–12), no transmission of HIV, HBV, or syphilis was documented by serology and nucleic acid testing (NAT) testing. Two patients transplanted with organs from HCV‐RNA‐positive donors, as expected, developed post‐transplant HCV infection. In conclusion, the use of organs from IRD was associated with a safe increase in the transplant procedures in our country.     

Impact of the OPTN transmissible diseases policy and US PHS increased risk donor guidelines on living donor candidates

Donor‐derived human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B virus (HBV) transmissions in transplantation have led to policies mandating assessment of donor behavioral history, and disclosure of donor increased risk (IR) status to recipients. Organ Procurement Transplantation Network (OPTN) policy safeguards were promulgated in the context of deceased donation, with its narrow time window for organ utilization and uncertainty about donor history. These policies have been applied to living donation without substantive data on risk of disease transmission in living donor transplantation. Unlike for deceased donors, the OPTN does not collect data on living donor IR status. Given the feasibility of thorough living donor evaluation via already‐mandated lab tests and clinical assessments, living donor IR assessment and associated disclosures may have limited benefit in improving recipient informed consent. Applying the current IR policy to living donors may also introduce unintended consequences to donors and recipients, causing donors psychological harm, delays in donation to avoid IR status disclosure, and potential withdrawal from donation. We suggest strategies that reduce risk of harm to donor candidates while maintaining policy compliance, and review additional approaches for evaluating risk of disease transmission in living donor candidates. Data on the risk of disease transmission by living donors are needed to inform policy modification.     

Estimated Risk of Human Immunodeficiency Virus and Hepatitis C Virus Infection among Potential Organ Donors from 17 Organ Procurement Organizations in the United States

To prevent unintentional transmission of bloodborne pathogens through organ transplantation, organ procurement organizations (OPOs) screen potential donors by serologic testing to identify human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection. Newly acquired infection, however, may be undetectable by serologic testing. Our objective was to estimate the incidence of undetected infection among potential organ donors and to assess the significance of risk reductions conferred by nucleic acid testing (NAT) versus serology alone. We calculated prevalence of HIV and HCV—stratified by OPO risk designation—in 13 667 potential organ donors managed by 17 OPOs from 1/1/2004 to 7/1/2008. We calculated incidence of undetected infection using the incidence‐window period approach. The prevalence of HIV was 0.10% for normal risk potential donors and 0.50% for high risk potential donors; HCV prevalence was 3.45% and 18.20%, respectively. For HIV, the estimated incidence of undetected infection by serologic screening was 1 in 50 000 for normal risk potential donors and 1 in 11 000 for high risk potential donors; for HCV, undetected incidence by serologic screening was 1 in 5000 and 1 in 1000, respectively. Projected estimates of undetected infection with NAT screening versus serology alone suggest that NAT screening could significantly reduce the rate of undetected HCV for all donor risk strata.     

Nucleic Acid Testing (NAT) of Organ Donors: Is the ‘Best’ Test the Right Test? A Consensus Conference Report

Nucleic acid testing (NAT) for HIV, HBV and HCV shortens the time between infection and detection by available testing. A group of experts was selected to develop recommendations for the use of NAT in the HIV/HBV/HCV screening of potential organ donors. The rapid turnaround times needed for donor testing and the risk of death while awaiting transplantation make organ donor screening different from screening blood‐or tissue donors. In donors with no identified risk factors, there is insufficient evidence to recommend routine NAT, as the benefits of NAT may not outweigh the disadvantages of NAT especially when false‐positive results can lead to loss of donor organs. For donors with identified behavioral risk factors, NAT should be considered to reduce the risk of transmission and increase organ utilization. Informed consent balancing the risks of donor‐derived infection against the risk of remaining on the waiting list should be obtained at the time of candidate listing and again at the time of organ offer. In conclusion, there is insufficient evidence to recommend universal prospective screening of organ donors for HIV, HCV and HBV using current NAT platforms. Further study of viral screening modalities may reduce disease transmission risk without excessive donor loss.     

Organs from deceased donors with false‐positive HIV screening tests: An unexpected benefit of the HOPE act

Organs from deceased donors with suspected false‐positive HIV screening tests were generally discarded due to the chance that the test was truly positive. However, the HIV Organ Policy Equity (HOPE) Act now facilitates use of such organs for transplantation to HIV‐infected (HIV+) individuals. In the HOPE in Action trial, donors without a known HIV infection who unexpectedly tested positive for anti‐HIV antibody (Ab) or HIV nucleic acid test (NAT) were classified as suspected false‐positive donors. Between March 2016 and March 2018, 10 suspected false‐positive donors had organs recovered for transplant for 21 HIV + recipients (14 single‐kidney, 1 double‐kidney, 5 liver, 1 simultaneous liver‐kidney). Median donor age was 24 years; cause of death was trauma (n = 5), stroke (n = 4), and anoxia (n = 1); three donors were labeled Public Health Service increased infectious risk. Median kidney donor profile index was 30.5 (IQR 22‐58). Eight donors were HIV Ab+/NAT‐; two were HIV Ab‐/NAT+. All 10 suspected false‐positive donors were confirmed to be HIV‐noninfected. Given the false‐positive rates of approved assays used to screen > 20 000 deceased donors annually, we estimate 50‐100 HIV false‐positive donors per year. Organ transplantation from suspected HIV false‐positive donors is an unexpected benefit of the HOPE Act that provides another novel organ source.     

Immediate administration of antiviral therapy after transplantation of hepatitis C‐infected livers into uninfected recipients: Implications for therapeutic planning

The practice of transplanting hepatitis C (HCV)‐infected livers into HCV‐uninfected recipients has not previously been recommended in transplant guidelines, in part because of concerns over uncontrolled HCV infection of the allograft. Direct‐acting antivirals (DAAs) provide an opportunity to treat donor‐derived HCV‐infection and should be administered early in the posttransplant period. However, evidence on the safety and efficacy of an immediate DAA treatment approach, including how to manage logistical barriers surrounding timely DAA procurement, are required prior to broader use of HCV‐positive donor organs. We report the results of a trial in which 14 HCV‐negative patients underwent successful liver transplantation from HCV‐positive donors. Nine patients received viremic (nucleic acid testing [NAT]‐positive) livers and started a 12‐week course of oral glecaprevir‐pibrentasvir within 5 days of transplant. Five patients received livers from HCV antibody‐positive nonviremic donors and were followed using a reactive approach. Survival in NAT‐positive recipients is 100% at a median follow‐up of 46 weeks. An immediate treatment approach for HCV NAT‐positive liver transplantation into uninfected recipients is safe and efficacious. Securing payer approval for DAAs early in the posttransplant course could enable need‐based allocation of HCV‐positive donor organs irrespective of candidate HCV status, while averting chronic HCV allograft infection.     

Estimated Benefits of Transplantation of Kidneys from Donors at Increased Risk for HIV or Hepatitis C Infection

Kidneys from organ donors who have behaviors that place them at increased risk for infection with human immunodeficiency virus (HIV) or hepatitis C virus (HCV) are often discarded, even if viral screening tests are negative. This study compared policies that would either 'Discard' or 'Transplant' kidneys from Centers for Disease Control classified increased-risk donors (CDC-IRDs) using a decision analytic Markov model of renal failure treatment modalities. Base-case CDC-IRDs were current injection drug users (IDUs) with negative antibody and nucleic acid testing (NAT) for HIV and HCV, comprising 5% of kidney donors. Compared to a CDC-IRD kidney 'Discard' policy, the 'Transplant' policy resulted in higher patient survival, a greater number of quality-adjusted life-years (QALYs) (5.6 vs. 5.1 years per patient), more kidney transplants (990 vs. 740 transplants per 1000 patients) and lower cost of care ($60 000 vs. $71 000 per QALY). The total number of viral infections was lower with the 'Transplant' policy (13.1 vs. 14.8 infections per 1000 patients over 20 years), because the 'Discard' policy led to more time on hemodialysis, with a higher HCV incidence. We recommend that kidneys from NAT-negative CDC-IRDs be considered for transplantation since the practice is estimated to be beneficial from both the societal and individual patient perspective.     

Transplantation of high‐risk donor organs: a survey of US solid organ transplant center practices as reported by transplant infectious diseases physicians

Abstract: Public Health Service (PHS) guidelines developed in 1994 provide guidance to minimize the risk of HIV transmission and to monitor recipients following the transplantation of “high‐risk” organs. There are no data on current practices or opinions of these policies by transplant infectious diseases (TID) physicians. An electronic survey was sent to all US solid organ transplatation centers with identified TID expertise as self‐reported to the American Society of Transplantation and Infectious Diseases Society of America. A total of 108 surveys were sent in December 2007 and 32 responses were received (30%). Thirty‐three percent of centers obtain only verbal, 52% verbal and written, and 14% do not obtain any special consent from recipients of organs from high‐risk donors (ROHRD). Post‐solid organ transplantation serologies for HIV, hepatitis B (HBV), and hepatitis C virus (HCV) are obtained at 40% of centers in ROHRD only, 20% in all recipients, and not performed in 40%; post‐solid organ transplantation nucleic acid testing (NAT) testing is carried out in 36–45% of centers in ROHRD, 11% in all recipients, and not performed in approximately 50% of centers. Only 22.7% of respondents believed current guidelines accurately represent what they consider to be high‐risk donors. There is significant variability in the acceptance and management of ROHRD in the US. Most TID experts do not feel that the current PHS guidelines accurately define high‐risk donors.     

Prevalence and Estimated Incidence of Blood-Borne Viral Pathogen Infection in Organ and Tissue Donors from Northern Alberta

To determine the potential safety benefit of introducing nucleic acid testing (NAT) in tissue and organ donors, the risk of virus transmission was examined in a Canadian population. Anonymous data on Northern Alberta tissue and organ donors from 1998 to 2004 were used to determine the seroprevalence and estimate the seroincidence and residual risk of HIV, HBV, HCV and HTLV infection. Of the 3372 donors identified, 71.1% were surgical bone, 13.2% were living organ and 15.6% were deceased organ/tissue donors. Seroprevalence was: HIV 0.00%, HBV 0.09%, HCV 0.48% and HTLV 0.03%. Incidence (/100,000 p-yrs) and residual risks (/100,000 donors) could only be estimated for HBV (24.2 and 3.9) and HCV (11.2 and 2.2). Risk estimates were higher for deceased donors than surgical bone donors. HCV had the highest prevalence and HBV had the highest estimated incidence. HIV and HTLV risks were extremely low precluding accurate quantification. In this region of low overall viral prevalence, HCV NAT would be most effective in deceased organ donors. In surgical bone donors the cost of implementing NAT is high without significant added safety benefit.     

Hepatitis C–associated focal proliferative glomerulonephritis in an aviremic recipient of a hepatitis C–positive antibody donor liver

Shortage of organs for liver transplantation (LT) and the availability of highly efficient pan-genotypic direct-acting antivirals (DAAs) against hepatitis C virus (HCV) have allowed the use of livers from HCV-positive antibody/negative nucleic acid test donors (dHCV Ab+/NAT−) into aviremic HCV recipients over the last few years. We report the case of a patient who received an LT from an HCV Ab+/NAT− donor and, after HCV viremic conversion, developed a nephrotic syndrome due to a focal proliferative glomerulonephritis early after LT. Patient's renal function and proteinuria resolved after successful treatment with DAAs. Renal and hepatic function remain normal over 24 months of follow-up. This case restates the success of LT using livers from dHCV Ab+/NAT− in aviremic recipients in the context of DAAs while illustrating the risk for potential complications associated with the HCV transmission and reinforcing the importance of early initiation of anti-HCV therapy.     

Pancreas transplantation from hepatitis C viremic donors to uninfected recipients

Despite utilization of hepatitis C viremic organs for hepatitis C naïve recipients (HCV D+/R-) in other solid organ transplants, HCV viremic pancreata remain an unexplored source of donor organs. This study reports the first series of HCV D+/R- pancreas transplants. HCV D+/R- had shorter waitlist times compared to HCV D-/R-, waiting a mean of 16 days from listing for HCV-positive organs. HCV D+/R- had a lower match allocation sequence than HCV D-/R-, and this correlated with receipt of organs with a lower Pancreas Donor Risk Index (PDRI) score. All HCV D+/R- had excellent graft function with a mean follow-up of 438 days and had undetectable HCV RNA levels by a mean of 23 days after initiation of HCV-directed therapy. The rates of infectious complications, reoperation, readmission, rejection, and length of stay were not impacted by donor HCV status. A national review of potential ideal pancreas donors found that 37% of ideal HCV-negative pancreas allografts were transplanted, compared to only 5% of ideal HCV-positive pancreas allografts. The results of the current study demonstrate the safety of accepting HCV-positive pancreata for HCV-naïve recipients and advocates for increased utilization of ideal HCV-positive pancreas allografts.     

Transplantation of hepatitis C virus (HCV) antibody positive,nucleic acid test negative donor kidneys to HCV negative patients frequently results in seroconversion but not HCV viremia

Anecdotal reports have suggested that transplantation of hepatitis C virus (HCV) antibody positive (Ab+)/nucleic acid test negative (NAT?) donor kidneys into HCV negative recipients is not associated with HCV transmission. We reviewed our center's outcomes of 32 HCV negative patients who received kidney allografts from 25 donors who were HCV Ab+/NAT?. The mean recipient age was 56.9 ± 12.1 years and the mean donor age was 41.5 ± 14 years, with a median Kidney Donor Profile Index (KDPI) of 68%. Twelve donors (48%) met Public Health Service (PHS) increased risk status. All patients received antithymocyte globulin induction followed by tacrolimus, mycophenolate mofetil, and steroid maintenance immunosuppression. With a mean follow‐up posttransplant of 10 ± 2.7 months, 1‐ and 3‐ month serum creatinine levels were 1.7 ± 0.8 and 1.3 ± 0.4, respectively, and patient and graft survival rates were 100% and 97%, respectively. Fourteen patients (44%) seroconverted and became HCV Ab+ posttransplant. However, all 32 patients were HCV RNA negative at 1‐ and 3‐ months posttransplant, and 27 and 8 patients tested at 6‐ and 12‐months posttransplant, respectively, remain HCV RNA negative. In conclusion, transplantation of HCV Ab+/NAT? kidneys to HCV negative recipients frequently causes HCV Ab seroconversion but not HCV viremia.     

Risk of Window Period Hepatitis‐C Infection in High Infectious Risk Donors: Systematic Review and Meta‐Analysis

The OPTN classifies high infectious risk donors (HRDs) based on criteria originally intended to identify people at risk for HIV infection. These donors are sometimes referred to as ‘CDC high risk donors’ in reference to the CDC‐published guidelines adopted by the OPTN. However, these guidelines are also being used to identify deceased donors at increased risk of window period (WP) hepatitis C virus (HCV) infection, although not designed for this purpose. The actual risk of WP HCV infection in HRDs is unknown. We performed a systematic review of 3476 abstracts and identified 37 eligible estimates of HCV incidence in HRD populations in the United States/Canada. Pooled HCV incidence was derived and used to estimate the risk of WP infection for each HRD category. Risks ranged from 0.26 to 300.6 per 10 000 donors based on WP for ELISA and 0.027 to 32.4 based on nucleic acid testing (NAT). Injection drug users were at highest risk (32.4 per 10 000 donors by NAT WP), followed by commercial sex workers and donors exhibiting high risk sexual behavior (12.3 per 10 000), men who have sex with men (3.5 per 10 000), incarcerated donors (0.8 per 10 000), donors exposed to HIV infected blood (0.4 per 10 000) and hemophiliacs (0.027 per 10 000). NAT reduced WP risk by approximately 10‐fold in each category.     

Liver,simultaneous liver-kidney,and kidney transplantation from hepatitis C-positive donors in hepatitis C-negative recipients: A single-center study

Transplantation of organs from hepatitis C virus (HCV)-antibody (Ab) and -nucleic acid test (NAT) positive donors into HCV-negative recipients has been proposed to expand the donor pool and shorten waiting times. Data on early single-center outcomes are lacking. Nineteen liver (LT, including seven simultaneous liver-kidney [SLKT]) and 17 kidney transplant (KT) recipients received organs from HCV (+) donors; of these, 13 were HCV NAT (+) in each group. All patients who received organs from HCV NAT (+) donors developed HCV viremia post-transplant except for 2 KT recipients. Patients were treated with a variety of direct-acting antiviral regimens, with high rates of sustained virologic response among those with at least 12 weeks of follow-up past the end of treatment: 12/13 (92%) and 8/8 (100%) among LT/SLKT, and KT recipients. Median time to treatment start was 42 days (interquartile range [IQR] 35-118 days) and 40 days (IQR 26-73) post-LT/SLKT and KT, respectively. One death occurred in a SLKT recipient unrelated to HCV or its treatment. There was no significant increase in rejection, proteinuria, or changes in immunosuppression in any group. Organs from HCV-viremic donors can be utilized for HCV-uninfected recipients with good short-term outcomes.     

Viral Nucleic Acid Testing (NAT) and OPO-Level Disposition of High-Risk Donor Organs

The use of Public Health Service/Centers for Disease Control and Prevention (PHS/CDC) high-risk donor (HRD) organs remains controversial, especially in light of a recent high-profile case of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) transmission. Nucleic acid testing (NAT), while more expensive and time consuming, reduces infectious risk by shortening the period between infection and detectability. The purpose of this study was to characterize HRDs and disposition of their organs by organ procurement organization (OPO), to measure NAT practices by OPO and to examine associations between NAT practices and use of HRD organs. We analyzed 29 950 deceased donors (2574 HRDs) reported to UNOS since July 1, 2004 and May 8, 2008. We then surveyed all OPO clinical directors about their use of NAT, average time to receive NAT results, locations where NAT is performed and percentage of the time NAT results are available for allocation decisions. In total, 51.7% of OPOs always perform HIV NAT, while 24.1% never do. A similar pattern is seen for HCV NAT performance, while the majority (65.6%) never perform HBV NAT. AIDS prevalence in an OPO service area is not associated with NAT practice. OPOs that perform HIV NAT are less likely to export organs outside of their region. The wide variation of current practice and the possibility that NAT would improve organ utilization support consideration for a national policy.     

The American Society of Transplantation Consensus Conference on the Use of Hepatitis C Viremic Donors in Solid Organ Transplantation

The availability of direct‐acting antiviral agents for the treatment of hepatitis C virus (HCV) infection has resulted in a profound shift in the approach to the management of this infection. These changes have affected the practice of solid organ transplantation by altering the framework by which patients with end‐stage organ disease are managed and receive organ transplants. The high level of safety and efficacy of these medications in patients with chronic HCV infection provides the opportunity to explore their use in the setting of transplanting organs from HCV‐viremic patients into non–HCV‐viremic recipients. Because these organs are frequently discarded and typically come from younger donors, this approach has the potential to save lives on the solid organ transplant waitlist. Therefore, an urgent need exists for prospective research protocols that study the risk versus benefit of using organs for hepatitis C–infected donors. In response to this rapidly changing practice and the need for scientific study and consensus, the American Society of Transplantation convened a meeting of experts to review current data and develop the framework for the study of using HCV viremic organs in solid organ transplantation.