Kidney transplantation from donors with active hepatitis C virus (HCV) viremia into HCV seronegative recipients expands the donor pool but raises questions about optimal prophylactic direct‑acting antiviral (DAA) strategies. The ideal duration of DAA prophylaxis after transplantation remains undefined. This retrospective analysis reports outcomes following a fixed 28‑day course of sofosbuvir/velpatasvir (SOF/VEL) initiated postoperatively in a Veterans Affairs kidney transplant cohort.
Investigators performed a retrospective review of all HCV seronegative adults who received a kidney from an HCV nucleic acid test (NAT) positive deceased donor at the VA Portland Medical Center between September 2017 and March 2025. All included recipients were treated with a 28‑day postoperative prophylaxis regimen of SOF/VEL.
The primary outcome was sustained virologic response measured 12 weeks after completion of prophylaxis (initial SVR12). Secondary outcomes assessed at 1 year included overall HCV treatment success rate (including retreatment when prophylaxis failed), biopsy‑proven acute rejection (BPAR), delayed graft function (DGF), estimated glomerular filtration rate (eGFR), liver enzyme abnormalities, cytomegalovirus (CMV) and BK virus viremia, adverse events attributed to DAA, and all‑cause mortality.
Initial SVR12 was defined as undetectable HCV RNA 12 weeks after finishing the 28‑day prophylaxis course. Patients with transient or persistent viremia after prophylaxis could have prophylaxis extended or receive full HCV treatment; overall SVR reflects achievement of virologic cure after any subsequent therapy.
Fifty patients met inclusion criteria. Mean age was 62.8 ± 10.9 years and 92% were male. Mean Estimated Post Transplant Survival (EPTS) score was 63.7 ± 29.2 and mean Kidney Donor Profile Index (KDPI) was 59.8 ± 19.6.
Initial SVR12 after completion of the 28‑day SOF/VEL prophylaxis was achieved in 46 of 50 patients (92%). Two of the patients who achieved initial SVR12 had their SOF/VEL prophylaxis extended to 12 weeks because of transient viremia prior to documented SVR12. Four patients (8%) failed the 4‑week prophylaxis regimen; these patients subsequently received HCV treatment and all achieved SVR, yielding a 100% overall SVR rate in the cohort.
Clinical outcomes and complications observed at 1 year were: delayed graft function (DGF) in 16% of patients, biopsy‑proven acute rejection (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 m2. No adverse events were attributed to the DAA regimen. One‑year all‑cause mortality was 2% (1 of 50), and the single death was reported as unrelated to HCV infection or DAA therapy.
On comparative analysis reported in the abstract, recipients who failed prophylaxis were older and had higher EPTS scores compared with those who did not fail. Mean age in the prophylaxis‑failure group was 72.3 ± 4.0 versus 62.0 ± 11.0 years in the success group (p = 0.030). Mean EPTS was 86.5 ± 19.1 in the failure group versus 61.8 ± 29.3 in the success group (p = 0.041). The abstract does not report other multivariable analyses or additional predictors.
No adverse events were attributed to SOF/VEL in this cohort according to the abstract. Two patients required an extended course of SOF/VEL to 12 weeks for transient viremia and were counted among the initial SVR12 successes. Overall, after retreatment for the four prophylaxis failures, the cohort achieved 100% SVR. One patient died within one year (2%), and that death was unrelated to HCV or DAA therapy.
In this single‑center Veterans Affairs retrospective cohort of 50 HCV seronegative kidney recipients from HCV NAT‑positive deceased donors, a 4‑week postoperative SOF/VEL prophylaxis regimen combined with HCV RNA surveillance and prompt treatment of failures was associated with a 92% initial SVR12 rate and 100% overall SVR after retreatment. Rates of DGF, BPAR, CMV and BK viremia, and 1‑year eGFR are reported, and no DAA‑attributable adverse events were recorded. Older age and higher EPTS scores correlated with prophylaxis failure in this sample. Detailed protocol elements such as monitoring cadence, exact virologic thresholds, and specific retreatment regimens were not provided in the abstract.