Transplantation of Kidneys from HCV Viremic Donors in the United States: A Missed Opportunity to Inform Clinical Decision Making and Health Policy

In this issue of JASN, Potluri and colleagues¹ report a marked increase in the availability and use of kidneys from HCV viremic deceased donors for transplantation as a result of the opioid epidemic and the advent of direct-acting antivirals (DAAs). Historically, transplantation of these kidneys was restricted to HCV-positive waitlist candidates and most were either not retrieved or discarded. DAAs now allow consideration of using kidneys from HCV viremic donors in both HCV-positive and HCV-negative waitlist candidates.

The study used national data collected by the Organ Procurement and Transplant Network (OPTN) between December 2015 and March 2019 and reported a nearly six-fold increase in the number of waitlist candidates willing to accept a kidney from a donor with any evidence of HCV infection, including a doubling of patients willing to accept a HCV viremic donor kidney. As a result, transplantation of kidneys from HCV viremic donors in HCV-negative patients now outpaces their use in HCV-positive patients. Although the nonuse of kidneys from HCV viremic donors remained higher than that of kidneys from HCV seronegative donors, discard rates declined and fewer kidneys with otherwise favorable donor characteristics were discarded. Of note, the utilization of such kidneys varied geographically and in several regions there were no transplants involving HCV viremic donors in HCV-negative recipients. This variation in part reflects the geography of the opioid epidemic, but also indicates variation in acceptance of viremic kidneys by the transplant community.

The increased acceptance and utilization occurred despite limited information about the long-term safety and efficacy of DAAs in the transplant setting, especially in facilitating transplantation for HCV-negative patients. The potential to use kidneys from HCV viremic donors in HCV-negative patients was demonstrated in two small studies involving a total only 20 patients.^2,3 Both studies reported sustained viral remission after DAA treatment but did not report long-term outcomes.

In contrast to the robust information regarding kidney utilization, this study provides limited information about the long-term safety of such transplants. The outcomes of 103 HCV-negative recipients of an HCV viremic donor kidney with at least 12 months of available follow-up, were compared with those among a rigorously matched cohort of recipients of HCV nonviremic donor kidneys. The authors found no difference in patient or allograft survival, and no difference in eGFR or reported acute rejection events. The eGFR of transplants using HCV viremic donors was similar in patients with and without serological evidence of HCV infection, suggesting that recipient serostatus does not affect the function of transplants from HCV viremic donors.

The promising short-term outcomes led the authors to challenge the continued inclusion of HCV donor infection in the calculation of the Kidney Donor Profile Index, an equation that predicts the risk of allograft failure that is used to determine the allocation of deceased donor kidneys. The authors believe that donor HCV status no may longer represent a negative prognostic factor for transplant failure in the era of DAAs. Given the absence of information about long-term patient and allograft survival, and the likely careful selection of HCV-negative recipients, it is premature to alter established allocation policy on the basis of this report.

Although the study provides important information to support the continued transplantation of kidneys from viremic donors in recipients with and without preexisting HCV infection, many critical questions, including the timing, duration, efficacy, and complications of DAA use in the transplant setting remain that cannot be addressed because of the limitations of OPTN data. Information regarding the donor HCV genotype, viral load, presence and effect of DAA resistance–associated substitutions, patient selection criteria, DAA and immunosuppressant regimens, and major complications including fibrosing cholestatic hepatitis is critical to inform the expanded use of kidneys from HCV viremic donors that the authors advocate for. Although requirements for additional data collection are often met with resistance, this information could have been added at minimal cost to the OPTN.

The study also raises new questions regarding the optimal allocation of HCV viremic kidneys. Specifically, should these kidneys be preferentially allocated to patients with preexisting HCV infection to minimize the overall health care costs of DAA treatment? Related to this issue is the optimal timing of treatment of HCV-positive waitlisted transplant candidates. Because of the increased utilization of HCV viremic kidneys in HCV-negative candidates, existing recommendations to defer HCV treatment in clinically stable HCV-positive candidates until after transplantation may warrant reconsideration if this approach fails to provide these patients with more rapid access to transplantation from a viremic donor. Given the large geographic variation in the utilization of HCV donors, such management decisions may vary between regions. This issue will also not be fully informed without additional data collection. Because HCV status is currently not collected at time of waitlisting, the timing of transplantation in HCV-positive candidates with a kidney from a donor with or without viremia may be difficult to predict.

The current uncoordinated approach to HCV transplantation in the United States provides an opportunity to reflect on the strengths and weaknesses of the transplant system. Recognizing the potential to significantly increase the supply of deceased donor kidneys in the DAA era, the American Society of Transplantation (AST) provided recommendations for the transplantation of organs from HCV-infected donors.⁴ The ability to rapidly bring together experts and key stakeholders to inform best practice is a strength of the transplant community. Unfortunately, the recommendations did not lead to a coordinated collaborative approach for using HCV-infected donor organs. The current report is unable to determine how many transplants involving HCV viremic donors in HCV-negative recipients were performed in an institutional review board approved study as recommended by the AST. In the absence of a government-funded multicenter study, as mandated by the HIV Organ Policy Equity Act of 2013 for the use of organs from HIV-infected donors, or an industry partner, the community lacks mechanisms for centers to collaborative to test innovative therapies (such as DAAs) in the real-world setting. Such collaborations should be enabled by the existence of a world leading transplant registry. To date, the OPTN registry has been underutilized to advance clinical innovations and this functionality should be developed. The report of Potluri and colleagues¹ reveals the depth of patient trust in their care providers to provide them with best evidence-based advice regarding their transplant options. It is our responsibility to ensure we maximize the information obtained from their experience to better inform decision making for future patients.

Disclosures

Dr. Gill and Dr. Formica have no disclosures. Dr. Levitsky is a speaker for Gilead.