Use Of Such Organs Research Articles

COVID-19 seropositive donors yield comparable post-lung transplant outcomes.

Recent reports have suggested that coronavirus disease 2019 (COVID-19) infection can cause pneumonitis even in the absence of clinical symptoms and COVID-19 associated pulmonary inflammation can persist resulting in long-term fibrosis. This single-center study utilized standardized immunological testing to determine whether lungs from COVID-19 seropositive donors, indicative of past COVID-19 infection, can be safely used for clinical transplantation. The study included 90 consecutive lung transplant procedures incorporating donor serological testing for past COVID-19 infection. Donors were negative for active COVID-19 infection and met institutional criteria to be used for lung transplantation. The outcomes of lung transplant recipients were compared between donors with and without serological evidence of past COVID-19 infection. No significant difference was found in post-transplant survival rates between recipients of lungs obtained from donors with serological evidence compared to those without. Additionally, there were no significant differences in primary graft dysfunction grade 3 rates or other post-transplant clinical parameters, such as operative time, ischemic time, extracorporeal membrane oxygenation use, intensive care unit stay, and hospital stay. Our findings suggest that lungs from COVID-19 seropositive donors, but not active COVID-19 infection are safe and feasible for transplantation, yielding comparable post-transplant outcomes to donors who are negative COVID-19 antibodies. This study supports the utilization of lungs from donors with historic COVID-19 infection as long as they meet current transplant criteria, potentially addressing the concerns related to the use of such organs.

Use of Hepatitis C Virus Antibody-Positive Donor Livers in Hepatitis C Nonviremic Liver Transplant Recipients

Given the shortage of available liver grafts, transplantation (LTx) of hepatitis C virus antibody-positive, nucleic acid test-negative (HCV Ab+/NAT-) livers into nonviremic HCV recipients can expand the donor pool. Having previously described the sentinel experience of HCV Ab+/NAT- allografts in nonviremic recipients, we report the growth and extended follow-up of this program for 55 patients compared with recipients of Public Health Services (PHS) increased-risk donor HCV Ab-/NAT- allografts. A prospective review of all HCV nonviremic LTx patients receiving HCV Ab+/NAT- organs between March 2016 and August 2018 was performed. All HCV Ab+/NAT- organ recipients underwent HCV testing at 3 months and 1-year post-LTx to determine HCV transmission. Fifty-five HCV nonviremic candidates received HCV Ab+/NAT- organs; 64% male, median age 59 years (range 36 to 69 years) and median Model for End-Stage Liver Disease score of 22.5. Two recipients were excluded due to death before HCV testing. The HCV disease transmission occurred in 5 recipients (9%). Of these, 4 (80%) underwent anti-HCV treatment with eradication of virus. No patient found to be negative at 3 months seroconverted at 1-year follow-up. No patients who received PHS increased-risk donor HCV Ab-/NAT- organs had viremia develop (0 of 57) and there was no difference in graft and renal function, complications, or survival between HCV Ab+/NAT- recipients and PHS increased-risk donor HCV Ab-/NAT- recipients. We report the largest experience with LTx from HCV Ab+/NAT- donors into 55 seronegative recipients with a HCV transmission rate of 9% with no late conversions at 1 year and no difference in function or graft loss compared with PHS increased-risk donor HCV Ab-/NAT- recipients. Due to availability of safe and effective HCV therapies, the use of such organs should be strongly considered to increase the donor organ pool.

Transplanting organs from hepatitis B positive donors: Is it safe? Is it ethical?

Liver transplant centres throughout the USA face a huge shortage of liver organs for their wait-listed patients. Various types of innovations are being considered for expansion of this donor pool. Organs that were previously deemed to be high risk are now being considered for transplantation. For the last 25years, hepatitis B core antibody (anti-HBc+) organs have been used for liver transplantation. While the initial transplantations did reveal a high incidence of de novo hepatitis (DNH) in the recipients, the medical knowledge and experience have evolved and this risk has been markedly decreased. In this paper, medical literature evaluating the safety of such organ transplants has been reviewed. There is strong evidence to suggest that using anti-HBc+ organs with appropriate prophylaxis after transplant is a safe practice with good patient and graft survivals. In the second half of the paper, we discuss whether it is ethical to use anti-HBc+ organs. We argue that the use of such organs is in compliance with the principles of medical ethics and that society at large benefits from the use of these organs. Hence, we recommend that the use of such organs is both safe and ethical and this practice should be continued in the future.

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 24years; 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>20000 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.

Hepatitis C transmission from seropositive, nonviremic donors to non-hepatitis C liver transplant recipients.

In this prospective cohort of non-HCV liver recipients receiving grafts from HCV antibody-positive/NAT-negative donors, the incidence of HCV transmission was 16%, with the highest risk conferred by donors who died of drug overdose; given the availability of safe and highly effective antiviral therapies, use of such organs could be considered to expand the donor pool. (Hepatology 2018;67:1673-1682).

Expanding access to transplantation with hepatitis C-positive donors: A new perspective on an old issue.

With the need for organs far exceeding supply, donors previously exposed to hepatitis B (HBV) and hepatitis C (HCV) viral infections should be considered for transplantation. Although many centers have protocols for transplanting organs from HBV core antibody-positive (HBcAb+) donors into select recipients, in the era of direct-acting antivirals (DAAs), a new focus should be placed on HCV-positive donors. The transmission rate from HCV antibody-positive (HCVAb+) nucleic acid testing negative (HCV NAT-) donors is expected to be very low, and we encourage use of such organs in HCV recipients provided a normal biopsy, appropriate counseling, and careful post-transplant monitoring. While transmission of HCV from HCV NAT+ donors is universal, the success of DAA in obtaining a sustained viral response in post-transplant recipients should make the use of these organs more appealing. We herein provide information to help guide the use of organs from HCV donors.

Resource implications of expanding the use of donation after circulatory determination of death in liver transplantation

In the United Kingdom, liver transplantation using donation after circulatory determination of death (DCDD) organs has increased steadily over the last few years and now accounts for 20% of UK transplant activity. The procurement of DCDD livers is actively promoted as a means of increasing the donor pool and bridging the evolving disparity between the wait-list length and the number of transplants performed. The objective of this retrospective study of a cohort of patients who were matched for age, liver disease etiology, and Model for End-Stage Liver Disease score was to determine whether differences in perioperative costs and resource utilization are associated with the use of such organs. Our results showed an increased prevalence of reperfusion syndrome in the DCDD cohort (P < 0.001), a prolonged heparin effect (P = 0.01), a greater incidence of hyperfibrinolysis (P = 0.002), longer periods of postoperative ventilator use (P = 0.03) and vasopressor support (P = 0.002), and a prolonged length of stay in the intensive therapy unit (ITU; P = 0.02). The peak posttransplant aspartate aminotransferase level was higher in the DCDD group (P = 0.007), and there was significantly more graft failure at 12 months (P = 0.03). In conclusion, we have demonstrated different perioperative and early postoperative courses for DCDD and donation after brain death (DBD) liver transplants. The overall quality of DCDD grafts is poorer; as a result, the length of the ITU stay and the need for multiorgan support are increased, and this has significant financial and resource implications. We believe that these implications require a careful real-life consideration of benefits. It is essential for DCDD not to be seen as a like-for-like alternative to DBD and for every effort to be continued to be made to increase the number of donations from brain-dead patients as a first resort.

Transplantation of solid organs procured from influenza A H1N1 infected donors

Following the influenza A H1N1 (swine flu) pandemic, there remains little evidence informing the safety of transplanting organs from donors suspected or diagnosed with H1N1. Limited guidelines from the major transplant societies leave the use of such organs at the discretion of individual transplant centres, and practice varies considerably both nationally and internationally. We present the largest published series of outcome following transplantation of organs from H1N1 positive donors and demonstrate that these organs can be transplanted safely and with good short-term outcome. We discuss our local policy for treatment of recipients with Oseltamivir.

Donors Positive for Hepatitis B Core Antibodies in Nonliver Transplantations

We reviewed available, particularly epidemiological data regarding transplantation of organs from donors positive for hepatitis B core antibodies (HBcAb) to evaluate the possibility of transmitting the disease. For nonhepatic organs, the risk is low: higher for lung but lower for kidneys and heart, according to the quantity of lymphoid tissue. The use of such organs is increasing owing to the worldwide organ shortage. Unfortunately, even if the use of HBcAb-positive donors does not seem to affect patient or graft survival, the United Network for Organ Sharing and United States Renal Data System registries do not have data on hepatitis B incidence after transplantation. Cohort data suggest that the use of such donors is safe if one follows suggested guidelines. In particular, recipients with no evidence of HBsAb should receive prophylaxis with either lamivudine or HB immunoglobulin. Our data show a 15%–20% incidence of HBcAb-positive donors, as in other European countries. The 1-year graft outcomes are good, with a 3% seroconversion rate to HB surface antigen.

Heavy metal bioaccumulation by the organs of Phragmites australis (common reed) and their potential use as contamination indicators

The concentrations of heavy metals in the roots, rhizomes, stems and leaves of the aquatic macrophyte Phragmites australis (common reed), and in the corresponding water and sediment samples from the mouth area of the Imera Meridionale River (Sicily, Italy), were investigated to ascertain whether plant organs are characterized by differential accumulation, and to test the suitability of the various organs for heavy metal biomonitoring of water and soil. Heavy metals considered were Cd, Cr, Cu, Hg, Mn, Ni, Pb, Zn. Results showed that belowground organs were the primary areas of metal accumulation. In particular, metal concentrations in plant organs decreased in the order of root > rhizome ≥ leaf > stem. All four organs showed significant differences in concentration for Cr, Hg, Mn, Zn, thus suggesting low mobility from roots to rhizomes and to aboveground organs. Although the organs followed different decreasing trends of metal concentration, the trend Mn > Zn > Pb > Cu was found in each plant organ. Mn showed the highest concentrations in all organs whereas the lowest concentrations regarded Cd and Cr in the belowground and aboveground organs, respectively. The toxic threshold was exceeded by Cr in roots, rhizomes and leaves, Mn in roots and leaves, Ni in roots. The highest average concentrations were found as follows: Cd, Hg, Pb, Zn in root, Cr, Mn, Ni in sediment, Cu in water. Positive linear relationships were found between heavy metal concentrations in all plant organs and those in water and sediment, thus indicating the potential use of such organs for pollution monitoring of water and sediment. Advantages of using plant species as biomonitors, especially Phragmites australis , were also discussed.

Transmission of human immunodeficiency virus and hepatitis C virus through liver transplantation

In November 2007, a liver transplant recipient was confirmed to have human immunodeficiency virus (HIV) and hepatitis C (HCV) infection after the organ procurement agency notified our institution that the donor has been HIV and HCV positive. We reviewed medical records and the collected blood sample results for HIV and HCV testing. A 66 year old female with nonalcoholic steatohepatitis cirrhosis underwent liver transplantation. The donor was a male who had sex with men who received multiple blood transfusions during resuscitation. Preoperative testing for HIV and HCV antibodies were negative for both donor and recipient. Ten months later, HIV and HCV were identified with nucleic acid testing in the recipient and in the stored donor sera. This is the first reported case of HIV transmission from solid organ transplantation in 20 years, and the first ever reported case of simultaneously transmitted HIV and HCV. The current case represents a high risk donor with newly-acquired HIV and HCV who transmitted the diseases during the window period of the infections. In this era of organ shortages one option would be avoidance of any high-risk donor organs. Another option would be to continue the use of such organs with appropriate informed consent, acknowledging the limitations of current screening tests for HIV and HCV. This report should serve as a wake-up call to the transplant community to consider revamping organ donor screening for HIV and HCV using nucleic acid testing as well as reconsidering the ongoing use of high-risk donors.

Poorer Outcomes for Recipients of Heart Allografts From HCV-Positive Donors

OVER THE PAST 30 YEARS, ORGAN TRANSPLANTAtion has evolved from an interesting experiment in human immunobiology to the most practical means of rehabilitating patients with end-stage dysfunction. At the same time, the requirement for chronic antirejection therapy, the presence of chronic or relapsing viral infection, and environmental exposures to a variety of opportunistic pathogens, have created a pathophysiological state and set of vulnerabilities rarely seen before. It has been estimated that 75% or more of organ transplant patients will have evidence of microbial replication and invasion in the first year posttransplant. Several principles have emerged from this experience. First, allograft rejection and invasive infection are closely linked, creating the need for a “therapeutic prescription” that has 2 components: an immunosuppressive program to prevent and treat rejection, and an antimicrobial strategy to make this safe. Changes in the immunosuppressive regimen should result in appropriate changes to the antimicrobial program. Second, bidirectional linkages between different processes are the rule, not the exception. Thus, hepatitis C virus (HCV) replication will increase the level of replication of cytomegalovirus (CMV) and vice versa, whereas CMV infection increases the incidence of Epstein-Barr virus–associated lymphoproliferative disease by a factor of 7 to 10. Third, perhaps the most important linkage is that in which viruses and allograft injury interact. The observation by Gasink and colleagues reported in this issue of JAMA that receipt of heart allografts from HCV-seropositive donors is associated with a poorer posttransplant survival is both expected and important. Expected because other viruses, such as CMV, appear to have this effect. Important because the chronic shortage of donors has resulted in attempts to expand the guidelines for accepting allografts, and there has been the hope that organs from HCV-positive donors could be used, particularly for critically ill organ recipients. The results of this study suggest that with current immunosuppressive therapy and antiviral prescription, the use of HCV-positive heart donors is not without hazard, even for HCV-positive recipients; that is, superinfection with HCV occurs, is clinically important, and cannot be generally recommended with current regimens of therapy. The question that emerges is whether special regimens can be developed that would allow the use of such organs with greater safety. In the meantime, the use of hearts from HCVpositive donors should be restricted to the critically ill who would not survive without an immediate transplant; whether such an approach is appropriate for other organs remains to be seen. The traditional view of the pathogenesis of allograft injury is that the triggering of a given pathway results in a unique histopathology. If a different pathway is involved, then the end result is a different histopathology that is recognizable. This so-called silo hypothesis was thought to provide insight into the pathogenesis of different clinical states. Compelling evidence now suggests that this view of pathogenesis is incorrect; rather than separate silos for each process, multiple paths exist that provide entrance into a final common pathway. Thus, such widely disparate processes as ischemia-reperfusion injury, immunologic injury, and certain infections (including HCV, CMV, and presumably other viruses such as human herpesvirus 6 and Epstein-Barr virus) can produce comparable histopathologic findings. The pattern of cytokine, chemokine, and growth factor release associated with each of these processes appears to be quite similar, thus explaining the final common pathway hypothesis. Similarly, the possibility of additive or synergistic effects due to multiple processes occurring simultaneously does not appear unreasonable. In addition, identification and control of these concomitant processes could improve the outcome in certain patients at risk for HCV-mediated processes. The clinical effect of HCV for patients undergoing organ transplantation can be divided into 2 general categories: the direct causation of acute and chronic liver injury, and the

Response to 'Viral Hepatitis Guidelines for Transplant Recipients'

Response to 'Viral Hepatitis Guidelines for Transplant Recipients'

Expanding the heart donor base

As increasing numbers of patients become eligible for heart transplantation, a large undersupply of suitable donor organs has developed. By matching recipient risk with donor risk, an effective expansion of the donor pool can occur while patient outcomes are maintained and organ wastage is minimized. As the safety of extended criteria is tested, the use of such organs can become more commonplace for certain recipients who might otherwise be excluded from transplantation. Future developments in organ preservation may allow for further use of marginal donor hearts.

Hepatitis C virus and organ transplantation.

Hepatitis C virus (HCV) is both the leading cause of cirrhosis and hepatic failure leading to liver transplantation and a cause of chronic hepatitis in approximately 10% of all transplant recipients. Beginning 5-10 years or more posttransplant, HCV causes progressive liver disease in a significant fraction of infected individuals and contributes to an increased incidence of opportunistic infection and hepatocellular carcinoma. The existence of multiple genotypes of HCV with differing biologic behaviors and the generation of antigenic diversity of the virus (quasispecies) during the course of infection, limit the capacity of the immune system to generate protective immunity. Antiviral therapy with interferon-alpha is effective in only a minority of transplant patients, and since allografts from HCV infected donors are quite efficient in transmitting the virus, great attention is paid to the appropriate use of organs from HCV-positive donors. At present, these organs should be particularly targeted for patients in emergent need of lifesaving heart, liver, or lung transplants. Issues requiring further investigation include the impact of viral superinfection on HCV-infected recipients of organs from HCV-infected donors and the use of such organs in seronegative patients who are older, diabetic, or highly sensitized, for whom quality of life issues may outweigh the long-term impact of HCV infection.

Policies in Europe on "marginal quality" donor livers

SummaryShortage of donor livers has led several liver transplant centres to widen their definition of liver donor suitability. We have assessed the function of liver grafts from "marginal" donors and attitudes to use of such organs. Over an 18-month period, livers used in 30 of 213 consecutive liver transplantations in Birmingham, UK, came from marginal donors (history of alcoholism, abnormal liver function test results, drug overdose that included paracetamol, advanced cardiovascular disease, sepsis, lengthy hypotension [systolic blood pressure <80 mm Hg for >1 h], high-dose inotropic drug use). 16 of these donors had been refused by other UK liver transplant centres, 11 on medical grounds. The controls were grafts retrieved from "good" donors (n=183) during the same period. All 30 grafts showed satisfactory early function but had greater day 1 (p=0·004) and peak serum aspartate aminotransferase (p=0·0008) values than control grafts. Graft and patient survival at 1 year in the two groups was similar (72% vs 73% and 80% vs 82%, respectively). To assess attitudes to marginal donor livers, a questionnaire outlining the details of these 30 donors was sent to the 80 centres in the European Liver Transplant Group, and 60 replied. Median immediate refusal rate of the marginal donors was 7/30 (range 0-18) and median outright acceptance rate was only 11/30 (1-26). Larger centres were less selective, with a significantly lower refusal rate (p=0·03).These results indicate that, because of existing liver donor criteria within Europe, usable donor livers are being unnecessarily refused on medical grounds.

AN APPROACH TO ORGAN SALVAGE FROM NON-HEARTBEATING CADAVER DONORS UNDER EXISTING LEGAL AND ETHICAL REQUIREMENTS FOR TRANSPLANTATION

Effective utilization of nonheartbeating cadaver donor organs is limited by the time required to obtain the necessary family consent prior to organ retrieval (a delay of at least 4-6 hr); this exceeds by far the maximum tolerance of kidneys to warm ischemia. Measures that could theoretically permit use of such organs include: (1) rapid in situ flush cooling; (2) continued in situ kidney cooling until permission for donation is secured; and (3) cell-membrane stabilization of vital organs, with only minimal invasion of the donor body. These measures were tested experimentally in dogs. Hemorrhagic shock was produced in mongrel dogs. One hour after cessation of heartbeat, a rapid perfusion tube was placed into the femoral artery; it was advanced, and its balloon was inflated in the aorta above the renal vessels. The kidneys were then flushed in situ with 1000 cc of cold preservation solution containing a calmodulin inhibitor, trifluoperazine. Two other catheters were inserted percutaneously into the peritoneal cavity for continuous intraperitoneal cold perfusion. Core temperatures of 4 degrees C were maintained in situ in the kidneys for 5 hr. Six hours after cardiac arrest, the kidneys were removed and preserved ex vivo at 4 degrees C for 24 hr, and were then transplanted into their respective hosts (n = 11), where they sustained life uneventfully. This method requires a 2-inch incision in the groin of the prospective donor, and two small stab wounds of the abdomen; i.e., semi-invasive procedures which are commonly performed in emergency rooms. The perfused body could then be released to the family if donation is denied. The recently documented increased willingness of the public to donate organs when the termination of life support is not an issue, and court decisions that have authorized the performance of nondeforming diagnostic procedures in cadavers without consent, suggest that the salvage of transplantable semi-invasive procedures described in this study may be useful in helping to alleviate the current shortage of transplantable organs. This technique can provide the time needed for families to consider the option of organ donation from nonheartbeating cadaver donors in an unhurried and unpressured manner, while preserving the viability of vital organs during the decision-making process.

Fetal organ and xenograft transplantation

The use of anencephalic fetuses and neonates as organ donors is technically feasible, and xenografts may be. Several ethical questions emerge, however, involving the appropriate use of such organs and what alterations, if any, in obstetric and neonatal management may be acceptable to increase the availability and likelihood of success of such organs.