*Purpose: Previous studies have shown that HCV D+/R- kidney transplantation is feasible using 8-12 weeks of DAAs. Utilization of abbreviated regimens may obviate the need for insurance approval and delay in therapy. We have previously shown very low transmission rates with a prophylactic peri-operative 7-day DAA (Sofusbuvir/Velpatasvir; SOF/VEL) regimen for ‘kidney-only’ transplants. Ezetimibe, a cholesterol lowering drug, has been shown to restrict HCV entry in hepatocytes in a humanized mouse model. Two published studies suggest that ezetimibe may be synergistic in reduction of HCV transmission from donors to recipients. Here we report our extended experience on 115 D+/R- kidney transplants with or without the addition of ezetimibe to the prophylactic regimen to investigate this effect.

*Methods: Data were collected via an Ethics Board approved prospective registry (REFORMHEPC). Inclusion criteria included: a) De-novo transplant; b) cPRA ≤50%; c) absence of synthetic liver dysfunction; and c) absence of active viral hepatitis. The primary outcome was donor HCV transmission at 90 days post-transplant. Patients were screened with HCV NAT at Day 7, 14, 28 and 90 post-transplant. All subjects received an initial dose of sofosbuvir/velpatasvir (SOF/VEL) +/- ezetimibe on day 0 ≤6 hours prior to transplant and then daily for a total of 7 days. Immunosuppression included induction with rabbit anti-thymocyte globulin followed by maintenance tacrolimus, mycophenolate and steroids. The protocol mandated initiation of full-course DAA therapy in case of 2 consecutive positive NAT tests.

*Results: A total of 115 D+/R- transplants (mean age=56 yrs) were included from May 2019-August 2021. The distribution of patients across the two groups was Group 1 (7 days prophylaxis with SOF/VEL alone; N=32) and Group 2 (7d prophylaxis with SOF/VEL plus ezetimibe; N=83). Patients enrolled in the two groups were demographically similar. Five patients (5/115; 4.3%; 95%CI:2%-10%) developed HCV viremia [1/32 (3%) in group 1, and 4/83 (4.8%) in group 2]. The donor genotypes (GT) are as follows: 3/5 (60%) GT3; 1/5 (20%) GT1b; 1/5 (20%) GT2b. All 5 patients with HCV transmission achieved SVR with 12 weeks of Glecapravir/Pibrentasvir therapy.

*Conclusions: Our data suggests that 7-days ultra-short duration pan-genotypic SOF/VEL prophylaxis was safe and largely effective in preventing donor-derived HCV transmission and has the potential of resulting in significant cost-savings by avoiding longer DAA therapy in a large majority of D+/R- KT. The addition of ezetimibe did not appear to provide any additional benefit in preventing HCV viral transmission.

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