Detection Is Protection: Adherence to Mandated HCV Testing After Liver Transplant

In March 2021, the Organ Procurement and Transplant Network (OPTN) mandated testing of hepatitis B virus, hepatitis C virus (HCV), and HIV for all transplant recipients at 4–8 wk posttransplant. The policy change removed terms that label an organ donor "increased risk" and promoted standardized early identification and treatment for hepatitis B virus, HCV, and HIV with a goal of increasing the number of organ transplants while minimizing the risk of viral transmission. Uniform and universal testing and reporting in place of unreliable for-cause testing enhances care and allows clarity on donor-derived viral infections, although adherence to this mandated universal testing has not been well established. This update has laid the foundation for examining the risk of donor-derived HCV transmission, particularly from liver donors whose nucleic acid test (NAT) is negative at the time of transplantation. Okumura et al1 evaluated adherence to the recently mandated test reporting for HCV as well as patient and graft outcomes among liver transplant (LT) recipients from donors who are HCV NAT negative and either HCV seropositive or seronegative. The authors specifically evaluated deceased donor LT recipients, who had previously tested negative for HCV NAT and antibody (Ab), from March 2021 to March 2023 using the OPTN database. In addition to adherence to mandated reporting of HCV testing, the authors evaluated incident HCV viremia, hospital length of stay, allograft rejection episodes, graft survival, and recipient survival. The authors found that among these 7447 LT recipients, adherence to HCV results reporting within 6 mo was complete in the majority of HCV Ab positive, NAT negative (85.3%) and HCV Ab negative, and NAT negative LT recipients (77.1%). Donor-derived HCV infection was rare (<1.3%) in both groups, but more common in recipients with HCV Ab positive, NAT negative donors (1.3%, 5/380) compared with HCV Ab negative, NAT negative donors (0.07%, 5/7067). As highlighted by the authors, this is the most robust data available regarding risk of transmission in these scenarios; most other studies are single center, and with small numbers. Rejection episodes, graft survival, and recipient survival were similar between the 2 groups at 1-y follow-up. Recipients of HCV Ab positive, NAT negative donor allografts trended toward a shorter length of index hospital stay at 9 versus 10 d and a lower Model for End-Stage Liver Disease score at transplant of 25 versus 26, suggesting that allografts from HCV seropositive, NAT negative deceased donors may offer an earlier path to LT. These study findings demonstrate the utility of a universal testing and reporting structure to evaluate donor-derived HCV infection. Adherence to mandated testing and reporting is critical for early detection and optimization of recipient outcomes, but remains incomplete in 14% and 23% of these cohorts. Adherence to mandated HCV results reporting was higher in the HCV Ab positive, NAT negative group compared with the HCV Ab negative, NAT negative group perhaps related to a perception of increased risk when a donor is HCV seropositive. Consistent with prior evaluations in the modern era, short- and medium-term outcomes including allograft rejection, graft survival, and patient survival are not appreciably different among these recipients.2 Advances in diagnostic testing with widely available reverse transcription polymerase chain reaction for HCV RNA has narrowed the window period for detection of HCV to 1–2 wk after infection and reduced the risk of disease transmission events; however, the risk is not eliminated. This is particularly true in the case of donors who are HCV Ab positive, NAT negative where very recent risk behavior(s) or false negative NAT results incurs increased risk for donor-derived HCV infection. Fortunately, in the era of direct-acting antiviral therapy, early identification of donor-derived HCV infection can result in HCV cure for nearly all patients.3 The landscape for HCV has undergone tectonic shifts in the past decade, especially as it relates to solid organ transplantation and continued vigilance will be needed to follow this evolution. Adherence to posttransplant HCV testing and reporting is particularly important considering reports suggesting emerging resistance and pan resistant strains of HCV.4 Additionally, more organ transplant programs are starting to use organs from donors who are hepatitis B surface antigen and/or DNA positive, for which careful posttransplant monitoring is needed both for patient care and understanding of risk of transmission and outcomes; this mandated testing should enhance safety and outcomes for these recipients as well.5 While the OPTN database facilitates data tracking on a national level for all transplant events, there is a significant rate of missing data which makes risk of donor-derived HCV infection in this study unreliable. The database also relies on HCV testing be entered into in the database, potentially underestimating the number of recipients tested. The timing of posttransplant HCV testing in LT recipients was not available which limits the true assessment of adherence and early detection. This also impacts the possibility of a positive HCV test representing a donor-derived infection as opposed to a newly acquired recipient infection; however, granular donor and recipient characteristics including risk factors for new HCV infection and previous HCV therapy are not available in the OPTN database. Ongoing efforts to monitor and improve adherence to mandated recipient testing are essential to understand the utilization of donor organs and optimize recipient outcomes. Studies that integrate donor and recipient risk, adherence to recipient testing, subsequent treatment and response to treatment can facilitate necessary shifts in the efforts of the transplant community and transplant policy as the understanding of transplant-associated infectious diseases evolves. Finally, because of risk associated with chronic viral infection, allograft fibrosis along with long-term graft and recipient survival warrant further evaluation in the case of HCV seropositive donors. Testing and reporting for donor-derived viral transmission remains critical to minimizing risk, clarifying informed consent, enlarging the organ donor pool, and optimizing transplant outcomes. Okumura et al1 provide valuable insights on adherence to OPTN testing mandates and risk of donor-derived HCV transmission. Future efforts to increase adherence to testing and reporting will be necessary for the transplant community to remain dynamic in risk assessment amidst an ever-evolving transplant landscape.