Outcomes After 4‐Week Course of Sofosbuvir/Velpatasvir Therapy in Hepatitis C Seronegative Recipients of Kidneys From Hepatitis C Viremic Deceased Donors

ABSTRACT Background Kidney transplantation from hepatitis C virus (HCV) viremic deceased donors into HCV seronegative recipients helps to expand the donor pool. The optimal duration of direct acting antiviral (DAA) prophylaxis remains undefined. Methods We performed a retrospective review of all HCV seronegative adults who received a kidney transplant from an HCV nucleic acid test (NAT) positive deceased donor at the VA Portland Medical Center between September 2017 and March 2025 and were treated with sofosbuvir/velpatasvir (SOF/VEL) prophylaxis for 28 days postoperatively. The primary outcome was sustained virologic response 12 weeks after completion of prophylaxis (initial SVR12). Secondary outcomes at 1 year included HCV treatment success rate, biopsy proven acute rejection (BPAR), delayed graft function (DGF), eGFR, liver enzyme abnormalities, CMV and BK viremia, adverse events, and all‐cause mortality. Results Fifty patients were included. The mean age was 62.8 ± 10.9 years, 92% were male, mean EPTS was 63.7 ± 29.2 and mean KDPI was 59.8 ± 19.6. Initial SVR12 after completion of prophylaxis was achieved in 46/50 (92%), out of which 2 patients had their SOF/VEL prophylaxis extended to 12 weeks because of transient viremia. Four patients (8%) failed prophylaxis and required HCV treatment with all achieving SVR (100% overall SVR). DGF occurred in 16%, BPAR in 12%, CMV viremia in 18%, and BK viremia in 16%. Mean 1‐year eGFR was 57.7 ± 18.7 mL/min/1.73 m 2 . No DAA attributable adverse events were recorded. One‐year all‐cause mortality was 2% (1/50) and was unrelated to HCV or DAA. Older age (72.3 ± 4.0 vs. 62.0 ± 11.0 years, p = 0.030) and higher Estimated Post Transplant Survival (EPTS) scores (86.5 ± 19.1 vs. 61.8 ± 29.3, p = 0.041) correlated significantly with prophylaxis failure. Conclusion A 4‐week SOF/VEL prophylaxis regimen coupled with HCV RNA surveillance and treatment appears to be safe and effective in a Veterans Affairs population.