*Purpose: To mitigate the organ shortage and underutilization of hepatitis C-infected deceased donor (HCV D+) organs, we evaluated the use of HCV D+ kidneys in HCV-uninfected recipients (HCV R-) with a short-course (2 weeks) of direct-acting antiviral (DAA) prophylaxis in a pilot trial (NCT04575896).

*Methods: HCV-negative kidney transplant candidates ≥ 18 years old were eligible. HCV D+ were ≤ 60 years old with a reactive HCV nucleic acid test, and terminal creatinine ≤ 5.0 mg/dL. Donor HCV genotype was determined post-transplant. DAA prophylaxis included one dose of glecaprevir/pibrenstavir pre-transplant and daily dosing for 2 weeks post-transplant. Recipient HCV RNA was measured post-transplant on treatment days 1, 4, 7, and week 2. Recipient HCV RNA was also measured post treatment at weeks 1, 2, 4, and 12.

*Results: Since 11/2020, we have performed 10 HCV D+/R- kidney transplants. Median donor age was 40, median KDPI 71; drug overdose was the cause of donor death in most (Table 1). Donor HCV RNA range was 629 to 1.1 X 10⁷ IU/mL (median 1.31 X 10⁶) with genotypes 1a (n=4), 2 (n=2), and 3 (n=4). One recipient had a grade 3 hyperbilirubinema possibly related to DAAs. Three recipients had no quantifiable HCV viremia post-transplant; seven had quantifiable low-level HCV viremia in the early posttransplant period. All ten recipients completed 2 weeks of DAAs and all ten recipients had an undetectable HCV RNA 12 weeks following completion of treatment. There was one graft failure 4.5 months post-transplant related to interstitial scarring.

*Conclusions: This pilot study provides proof-of-concept that 2-week DAA prophylaxis in HCV D+/R- kidney transplantation is well-tolerated and prevents transmission of HCV to the recipient.

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