Expanded Experience with Ultra-Short Duration Pangenotypic Direct Acting Anti-Viral (DAA) Prophylaxis to Prevent Virus Transmission from Hepatitis C Viremic (HCV) Donors to Hepatitis C Negative Kidney Transplant Recipients (KT)
I. Yakubu, D. Kumar, A. Sharma, M. Levy, L. Kamal, G. Gupta
Virginia Commonwealth University, Richmond, VA
Meeting: 2022 American Transplant Congress
Abstract number: 554
Keywords: Hepatitis C, Kidney transplantation
Topic: Clinical Science » Infection Disease » 27 - Non-Organ Specific: Viral Hepatitis
Session Information
Session Time: 5:30pm-7:00pm
Presentation Time: 5:40pm-5:50pm
Location: Hynes Room 312
*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.
To cite this abstract in AMA style:
Yakubu I, Kumar D, Sharma A, Levy M, Kamal L, Gupta G. Expanded Experience with Ultra-Short Duration Pangenotypic Direct Acting Anti-Viral (DAA) Prophylaxis to Prevent Virus Transmission from Hepatitis C Viremic (HCV) Donors to Hepatitis C Negative Kidney Transplant Recipients (KT) [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/expanded-experience-with-ultra-short-duration-pangenotypic-direct-acting-anti-viral-daa-prophylaxis-to-prevent-virus-transmission-from-hepatitis-c-viremic-hcv-donors-to-hepatitis-c-negative-kidney/. Accessed October 9, 2024.« Back to 2022 American Transplant Congress