EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Objectives: The inadequate supply of transplantable organs necessitates new approaches to donor screening while avoiding transmission of infections. Donor-derived infections are well described. Multiple changes have occurred in donor management and organ utilization, including increased recognition of and therapies for viral infections, the emergence of multidrug antimicrobial-resistant organisms, and identification of some uncommon viral infections transmitted with allografts to clusters of recipients. Donor evaluation has been impacted by substance use-associated deaths and routine use of serologies and nucleic acid testing for hepatitis C virus, hepatitis B virus, and human immunodeficiency virus. Improved assays are needed to prevent infectious transmissions.
Materials and Methods: The MGH Transplant Center reviewed experience with recipients of organs from donors meeting donor risk criteria and tracked all recipients for possible exposures to hepatitis C virus, hepatitis B virus, and human immunodeficiency virus. This required development of an electronic database to document microbiologic testing data.
Results: Database enhancements allowed tracking of serologic testing. Among our organ recipients, no transmissions of the studied viruses were identified by nucleic acid testing or clinically. Multiple patients had positive serologic assays for tested viruses; all recipients were retested, and appropriate inter-ventions were introduced if the test was confirmed. Some false-positive serologies resulted from recent hepatitis B virus vaccination, receipt of blood products, or transmission of donor B cells with tissues.
Conclusions: Organ transplant from donors meeting donor risk criteria for disease transmission can be performed safely with appropriate informed consent and rigorous pre- and posttransplant microbiological testing. Enhanced compliance with vaccination for hepatitis B virus should be tracked. New sequencing technologies developed for investigation of undiag-nosed infections and in xenotransplantation may inform future directions for donor screening. Such tools may increase the safe utilization of organs from donors who have potential risk for transmission of infection to recipients.

Key words : Hepatitis B virus, Hepatitis C virus, Human immunodeficiency virus, Infectious disease transmission, Metagenomic sequencing

Organ transplant is the therapy of choice for end-stage organ failure. Unexpected transmission of infection from donors to recipients is uncommon, but such events are incompletely reported and investigated.^1,2 The impact of such infections is amplified by the immunosuppressive drugs used to prevent immunological graft rejection. In immunosuppressed hosts, for example, the transmission of infection due to West Nile virus manifests more often as invasive neurological disease versus the same infection in normal hosts.^3-6 Certain infections are expected complications of transplant, including cytomegalovirus, BK polyomavirus, or Epstein-Barr virus. Others are unexpected and may be associated with significant morbidity in recipients. Such unexpected infections occur in less than 0.2% to 1.7% of solid-organ transplant recipients.^7-12

In the past decade, improved diagnostic assays and the availability of effective therapies for hepatitis C virus (HCV), hepatitis B virus (HBV), and human immunodeficiency virus (HIV) have facilitated use of organs from individuals considered to meet donor risk criteria for transmission of HIV, HBV, and HCV, notably from those dying from complications of drug intoxication.^13,14 The use of organs from donors infected with HCV, for example, is further complicated by delays in transfer of data relevant to donor viral loads and genotype of virus because such data are often available only after transplant. Testing both before and after transplant allows detection of unexpected transmissions, notably those occurring in the window period of viral infection before seroconversion develops.^1,15-18 Over the same period, the availability of improved microbiologic diagnostic assays such as meta-genomic sequencing tools have started to contribute to successful detection of less common pathogens associated with organ transplant.

Given the regulatory mandates for screening of organ recipients for common viral infections and the high incidence of opioid-associated deaths in the regional pool of deceased organ donors, we have reviewed our single-center experience with testing and documentation of HIV, HCV, and HBV testing.

Materials and Methods

This study was conducted by the Massachusetts General Hospital Transplant Center as a quality initiative and to address national regulatory requirements for recipient screening. Recent US Organ Procurement and Transplant Network Policies 15.2 and 15.3 require all transplant recipients to have pretransplant and posttransplant infectious disease testing performed at specific intervals according to the following protocols. (1) Upon transplant admission and prior to vascular anastomosis, patients must be tested for HIV antibody/antigen, HBV surface antigen (HBVsAg), HBV surface and core antibody (HBVsAb, HBVcAb), and HCV antibody; also, nucleic acid testing (NAT) for HIV, HBV, and HCV is required. (2) The NAT assays for HIV, HCV, and HBV must be performed between 28 and 56 days after transplant. (3) For liver transplant patients, the NAT assay for HBV must be performed between 11 and 13 months after liver transplant.

Regulatory review includes assessment of transplant programs for compliance at site surveys. To achieve compliance with these policies, the Massachusetts General Hospital Transplant Center Compliance Program worked with the team in Transplant Infectious Disease for the development of clinical protocols, including appropriate referrals for data review for any positive assay results. The institutional database team assisted with creation of admission order sets and database tracking reports to assist clinical teams. Subsequently, and according to staff education regarding the new procedures, the Transplant Center’s Quality and Compliance Team instituted an auditing/tracking process to ensure compliance.

Data on regional organ procurement from deceased donors with substance toxicity or opioid toxicity were obtained from New England Donor Services for the same time periods.

In 2016, over 40% of deceased donor organs procured in United Network for Organ Sharing region 1 (New England) were designated as meeting Public Health Service Donor Risk Criteria for infectious disease transmission, compared with ~20% nationally. In 2020, the rate of opioid-associated deaths among organ donors remained at 27% compared with 16% nationally. These donors tended to be young, first-time intravenous users of heroin. At the same time, organ shortages and patient acuity in wait-listed patients in US Region 1 (New England) are among the highest in the nation. Thus, the impetus to optimize use of donors was great in this region.

Assessment of compliance with admission serology and NAT testing in the most recent year (March 2021 to May 2022) included 365 transplant recipients, of which 92% had complete serological and NAT testing on admission or prior to anastomosis. Of these, 5 patients tested positive for HBVsAg, but subsequent repeat testing showed negative results, reflecting recent HBV vaccination. One patient had a false-positive HBV NAT assay result, and 2 patients had false-positive test results for HIV antibody/antigen.

However, 1 patient had a positive HIV antibody/antigen test result that was confirmed, and this patient is now on antiretroviral therapy after successful transplant. Regulatory-compliant posttransplant NAT retesting was completed in the correct timeframe and also provided valuable information. Retesting was completed in 68% of recipients within 28 to 56 days, with some false-positive results from NAT assays for HBV (n = 1), HCV (n = 1), and HBVcAb (n = 2). Two patients were confirmed positive for HBVcAb and treated for HBV infections after confirmation by NAT.

Of 1636 patients awaiting transplant, the program identified 846 patients who were nonimmune and required revaccination for HBV and an additional 118 patients (7%) who required primary vaccination. These patients have been scheduled. The rates of wait-listed patients requiring vaccination varied in proportion to program size.

Organs from donors considered to pose a potential risk for infectious disease transmission can be transplanted safely with appropriate informed consent and rigorous pretransplant and posttransplant microbiological testing. Our experience has also improved pretransplant vaccination compliance for HBV. Presently, although donor screening may be limited by inherent deficiencies in medical histories and occasional false-negative serologic testing, testing has been successful in most recipients. Donor and recipient screening might be improved in a variety of ways, including laboratory proficiency testing and test validation, faster communication of assay data, and greater flexibility in the screening process to reflect new epidemiology (eg, SARS-CoV-2), regional variability of endemic pathogens, and the donors’ epidemiologic histories (travel and immigration). Further investigation of the effects of donor characteristics (brain death, transfusion, colloid resuscitation, timing) and sample management relative to procurement is needed. In addition, the value of new technologies such as whole-genome sequencing in the detection of novel pathogens needs to be explored. Among the greatest challenges are data management and the need to develop databases capable of tracking microbiologic data for transplant candidates and informing transplant professionals regarding gaps in vaccinations and unexpected exposures. Standardized algorithms are required for real-time discrimination of true and false-positive assays and to facilitate referrals for expert patient management. All of these goals must be achieved with sensitivity to cost, clinical effectiveness, and effect on the available organ supply.

Volume: 20 Issue: 8 August 2022 - Supplement - 4

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