Donor Derived Cell Free DNA in Recipients of Hepatitis C Viremic Donors as a Possible Marker of a Pro-Inflammatory State Causing Graft Injury

Abstract

Since the highly effective Direct-Acting Antiviral (DAA) therapies have been available for treatment of HCV, transplant centers have begun using organs from HCV infected donors followed by treatment with DAAs. Epidemiological studies have shown that HCV may be associated with an increase atherosclerosis and it has been hypothesized that this is caused by activation of an immunological or inflammatory response. HCV infection of endothelial cells may promote endothelial dysfunction and early atherogenesis. The question arises, could acute HCV that is treated expeditiously, cause an inflammatory response leading to rejection or CAV in the heart transplant population. We plan to compare all recipients at our institution enrolled in the Surveillance HeartCare Outcomes Registry (S.H.O.R.E.) for increased donor derived cell free DNA (dd-cf DNA). They will be placed in 3 population categories: 1) Recipients of Non HCV donors, 2)Recipients of NAT positive donors and 3) Recipients of Antibody positive, NAT negative donors. After solid organ transplantation, donor-derived cell-free DNA circulates in the recipient's blood, and accounts for only a small fraction of total cfDNA (recipient plus donor-derived). During graft injury high amounts of donor-derived cell-free DNA (dd-cfDNA) are shed into the blood stream. HeartCare assesses heart health by measuring both immune activity and dd-cfDNA. The recommended threshold for Cell injury is greater than 0.2 % dd-cf DNA. We will compare populations by episodes of rejection, type of rejection and CAV at one year. At our institution there are currently 6 recipients of donor hearts that were HCV NAT positive and 3 recipients of HCV antibody positive but NAT negative. Participants will receive HeartCare at routinely scheduled intervals of every other month starting at month 4 for the first year and then quarterly out to 5 years post-transplant. We will compare populations by episodes of rejection, type of rejection and CAV at one year.