Purpose: Hepatitis C virus (HCV) infection in kidney transplant recipients (KTRs) is common and can impact on patient and graft survival rates. The efficacy and safety of direct-acting antivirals (DAAs) to treat genotype-4 HCV-infected KTRs have not been fully established.
Methods: A prospective, single-arm, single-center study was conducted at Mansoura Urology/Nephrology Center (Mansoura University, Egypt). 114 HCV RNA(+) genotype 4 KTRs were enrolled in this study after a hepatology consultation and consented to start treatment with interferon-free DAAs. A sofosbuvir-based regimen was given to 109 recipients that had creatinine clearance (Crcl) of > 30 mL/min/1.73 m2. Ritonavir-boosted paritaprevir/ombitasvir was prescribed to five recipients with Crcl < 30 mL/min/1.73 m2.
Results: The mean age of the cohort was 45.2 ± 11.2 years; most were male. The mean duration with a transplant was 14.2 ± 3.5 years, with different immunosuppressive regimens, mostly based on calcineurin inhibitors. A rapid virological response (RVR), i.e., clearance of viral load, was achieved in 100% at 4 weeks after starting treatment. All patients had a sustained virological response (SVR) at 12 and 24 weeks posttreatment, with one exception. During DAA therapy serum creatinine increased in 12 patients. In three, this was concomitant with elevated calcineurin inhibitor and sirolimus trough levels. Graft biopsies were performed in 8 of these 12 patients: these revealed an acute rejection in 4 cases (acute cellular rejection grade-1A: n = 2, and grade-1B: n = 2). The rejection episodes occurred at 4-6 weeks after starting treatment.
Conclusion: DAAs were highly efficacious and safely treated genotype-4 HCV-infected KTRs and had no significant adverse effects on graft function/survival.
Keywords: Direct antiviral agents (DAA); Drug interactions; HCV infection; Kidney transplantation; Sofosbuvir.