Direct-Acting Antiviral Prophylaxis in Kidney Transplantation From Hepatitis C Virus-Infected Donors to Noninfected Recipients: An Open-Label Nonrandomized Trial

Abstract

Background: Given the high mortality rate for patients with end-stage kidney disease receiving dialysis and the efficacy and safety of hepatitis C virus (HCV) treatments, discarded kidneys from HCV-infected donors may be a neglected public health resource.

Objective: To determine the tolerability and feasibility of using direct-acting antivirals (DAAs) as prophylaxis before and after kidney transplantation from HCV-infected donors to non-HCV-infected recipients (that is, HCV D+/R- transplantation).

Design: Open-label nonrandomized trial. (ClinicalTrials.gov: NCT02781649).

Setting: Single center.

Participants: 10 HCV D+/R- kidney transplant candidates older than 50 years with no available living donors.

Intervention: Transplantation of kidneys from deceased donors aged 13 to 50 years with positive HCV RNA and HCV antibody test results. All recipients received a dose of grazoprevir (GZR), 100 mg, and elbasvir (EBR), 50 mg, immediately before transplantation. Recipients of kidneys from donors with genotype 1 infection continued receiving GZR-EBR for 12 weeks after transplantation; those receiving organs from donors with genotype 2 or 3 infection had sofosbuvir, 400 mg, added to GZR-EBR for 12 weeks of triple therapy.

Measurements: The primary safety outcome was the incidence of adverse events related to GZR-EBR treatment. The primary efficacy outcome was the proportion of recipients with an HCV RNA level below the lower limit of quantification 12 weeks after prophylaxis.

Results: Among 10 HCV D+/R- transplant recipients, no treatment-related adverse events occurred, and HCV RNA was not detected in any recipient 12 weeks after treatment.

Limitation: Nonrandomized study design and a small number of patients.

Conclusion: Pre- and posttransplantation HCV treatment was safe and prevented chronic HCV infection in HCV D+/R- kidney transplant recipients. If confirmed in larger studies, this strategy should markedly expand organ options and reduce mortality for kidney transplant candidates without HCV infection.

Primary funding source: Merck Sharp & Dohme.

Figure 1. Pre- and Post-transplant HCV RNA Among HCV-uninfected Recipients of HCV+ Donor KT

HCV plasma RNA log₁₀ IU/mL pre-transplant, during DAA treatment on post-operative day 1, post transplant weeks 1, 2, 4, 8 and 12 and after DAA treatment on follow-up weeks 4, 8, and 12. Lower limit of quantification is 15 IU/mL.

Figure 2. Post-transplant Liver Function Tests Among HCV-uninfected Recipients of HCV+ Donor KT

(A) ALT values and (B) AST values measured at baseline and during post-transplant follow up. *Missing for one patient

Figure 3. Pre- and Post-Transplant HCV-specific CD8+ T cell Responses among Among HCV-uninfected Recipients of HCV+ Donor KT

The number of positive peptide pools identified for each recipient pre-transplant and at follow-up week 8 post-transplant are shown. T cell responses were measured by IFN-γ ELISpot using a matrix of 6 peptide pools containing overlapping peptides of optimal cytotoxic T lymphocyte HCV epitopes. Pools with > 50 spot forming cells/million PBMC were considered positive.