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.

Utilization of increased risk for transmission of infectious disease donor organs in solid organ transplantation: Retrospective analysis of disease transmission and safety.

The inadequate supply of transplantable organs necessitates new approaches to organ availability. Serologies and nucleic acid testing (NAT) for hepatitis C virus (HCV), hepatitis B virus (HBV), and human immunodeficiency virus (HIV) are used in microbiologic screening of potential organ donors. Organs from donors considered at "high risk" (Centers for Disease Control and Prevention, CDC 1994) or "increased risk" (U.S. Public Health Service, PHS 2013) for transmission of viral infection to recipients may provide an expanded source of organs for transplantation. We review a single-center experience with 257 adult organ recipients of organs from donors meeting either CDC 1994 or PHS 2013 risk criteria between 2011 and 2016. Tracking these transplants required modification of the Transplant Center electronic database to identify all recipients of increased-risk donor (IRD) organs, documentation of informed consent, and microbiologic testing data. No transmissions of HIV, HBV, or HCV were identified by NAT or clinically. Nine patients developed positive serologic assays for one of the tested viruses; all recipients were retested and remain negative by NAT. Notably, post-transplant HBV core serologies reverted to negative on re-testing; these positive serologies are likely false positives caused by receipt of blood products. Use of IRD organs can be performed safely with appropriate informed consent and rigorous pre- and post-transplant microbiological testing.

Donor-Derived Infections: Monitoring of Posttransplant Infections and Safety Lessons From the Opioid Epidemic.

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 interventions 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 undiagnosed 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.