Pre- and post-transplant treatment with direct-acting antiviral medications appears safe and may prevent chronic hepatitis C virus (HCV) infection in HCV-negative patients receiving a kidney from an HCV-positive donor, a small study found.
Researchers studied 10 HCV-negative recipients of 10 HCV-positive donor kidneys in an open-label, nonrandomized trial to determine the tolerability and feasibility of using prophylaxis with direct-acting antiviral therapy before and after transplant.
All transplant recipients received 100 mg of grazoprevir and 50 mg of elbasvir immediately before transplant and continued receiving this combination for 12 weeks. Recipients who received organs from donors with HCV genotype 2 or 3 infection also received 400 mg of sofosbuvir for 12 weeks of triple therapy. The primary safety outcome was incidence of adverse events related to direct-acting antiviral treatment, and the primary efficacy outcome was the proportion of recipients who had an HCV RNA level below the lower limit of quantification 12 weeks after prophylaxis. Results of the study, which was funded by Merck Sharp & Dohme Corp., were published March 6 by Annals of Internal Medicine.
Results of HCV antibody screening and qualitative HCV nucleic acid testing were positive in all 10 donors. Among the nine donors with detectable viral loads, median HCV load was 62,400 IU/mL (range, 104 to 4,645,289 IU/mL). Donor HCV genotypes were 1a (n=3), mixed 1a–3 (n=1), and 2 (n=2); in four cases, HCV genotype could not be determined because of insufficient HCV RNA levels.
Seven recipients completed treatment with only grazoprevir-elbasvir daily for 12 weeks, because their donors were infected with wild-type HCV genotype 1a or because genotype was unknown due to an insufficient HCV RNA level. Because no patients received a kidney infected with HCV genotype 1a with NS5a RAS, adding ribavirin to treatment was not necessary. Three recipients had sofosbuvir added to their grazoprevir-elbasvir regimen after their donors' HCV infection was identified as non-genotype 1 or 4. None of the recipients required a delay in sofosbuvir treatment or modification in sofosbuvir dosage. Among the 10 organ recipients, no treatment-related adverse events occurred, and HCV RNA was not detected in any recipient 12 weeks after treatment.
The researchers wrote, “If confirmed in larger studies, this approach should markedly expand organ options and reduce mortality for kidney transplant candidates without HCV infection.”