Mentored research in solid organ transplantation: outcomes using organs from Hepatitis C virus infected donors for uninfected recipients

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PROJECT SUMMARY Solid organ transplantation using kidneys, hearts or lungs extends life and improves quality of life for patients with end-stage organ disease. Unfortunately, the US waiting list exceeds 120,000 people. Many patients on the kidney transplant wait-list must wait over 5 years for an organ. For the elderly and some other patient groups, death on the waiting list is more likely than transplant. Substantial health deterioration or death on the waiting list are common outcomes for patients in need of a heart or lung transplant. Yet, over 800 kidneys and hundreds of viable hearts and lungs from deceased donors with hepatitis C virus (HCV) were discarded in 2016; hundreds more organs were never procured because of the perception that no center will accept them. The reluctance to transplant HCV-infected organs stems from historical studies showing elevated rates of allograft rejection. HCVinfection may carry other inflammatory consequences, includingglomerular injury to the kidney allograft, vasculopathy, or susceptibility to other infections. Additionally, HCV-infection carries social stigma, which may contribute to reluctance from patients to accept the organs. In this context, new direct acting antivirals (DAAs) with cure rates of >95% and few side effects have transformed HCV treatment and prompted some transplant clinicians to view discarded HCV-infected organs as a valuable opportunity for waitlisted patients with and without pre-existing HCV. However, it is unknown if DAAs will fully mitigate the risks of donor- derived HCV. As a result, transplant leaders have asserted the need for high quality studies to assess outcomes when HCV-infected organs are transplanted into HCV-negative recipients. Dr. Reese's research group leads a series of highly innovative trials and related scientific studies to better characterize outcomes for recipients of HCV-infected organs. These endeavors have created substantial opportunities for direct patient contact and the experience of leading important analyses of patient outcomes for Dr. Reese's mentees. The overarching goal is to characterize immunologic, infectious, allograft function and quality of life outcomes of HCV-negative recipients of HCV-infected organs. Specifically, we will determine if, compared to recipients of HCV-negative organs, recipients of HCV-infected organs experience a higher risk of the outcomes of 1) organ rejection and donor specific antibody and 2) cytomegalovirus infection. We will also determine if recipients of HCV-infected kidneys have non-inferior allograft function compared to recipients of HCV-negative kidneys. Finally, will also describe the experience and concerns of HCV-infected organ recipients and caregivers using mixed-methods. These aims provide not only training opportunities for the mentor, but also valuable training and research experiences for mentees at all levels. The opportunities for mentee involvement in the POR being proposed and direct patient contact make this project ideal for K-24 support.