Preemptive Treatment With Elbasvir and Grazoprevir for Hepatitis C-Viremic Donor to Uninfected Recipient Kidney Transplantation

Abstract

Introduction: Long wait times for kidney transplants have prompted investigation into strategies to decrease the discarding of potentially viable organs. Recent reports suggest that kidneys from hepatitis C virus (HCV)-infected donors may be transplanted into HCV-naive donors followed by direct-acting antiviral therapy.

Methods: This was a pilot clinical trial to transplant kidneys from HCV-infected donors into HCV-naive recipients with preemptive use of elbasvir and grazoprevir for 12 weeks. The primary outcome was sustained virologic response 12 weeks after completion of therapy. Secondary outcomes were safety, quality of life, and early viral kinetics.

Results: A total of 33 patients were screened, and 8 underwent kidney transplantation from a HCV-viremic donors from August 2017 to March 2019. The median donor kidney donor profile index was 31% (range, 29%-65%), and patients who underwent transplantation waited a median of 6.5 months (range, 1-19 months). None had detectable HCV viremia beyond 2 weeks post-transplantation, and all achieved sustained virologic response 12 weeks after therapy (SVR12). There were no study-related severe adverse events. One patient experienced early graft loss due to venous thrombosis, whereas the remaining 7 patients had excellent allograft function at 6 months.

Conclusion: Preemptive elbasvir and grazoprevir eliminated HCV infection in HCV-naive patients who received a kidney transplant from an HCV-infected donor.

Keywords: direct-acting antivirals; hepatitis C virus; kidney transplantation; organ allocation.

Graphical abstract

Figure 1

Flow of patients from enrollment to transplantation. HCV, hepatitis C virus.

Figure 2

Hepatitis C–virus (HCV) RNA levels among recipients of HCV-viremic kidneys. Detectable but unquantifiable HCV RNA is shown as 14 IU/ml, as the lower limit of quantification for our assay was 15 IU/ml. End of treatment occurred on day 84 post-treatment (PT). Twelve weeks post-treatment occurred on day 168.

Figure 3

Post-transplantation kidney function among recipients of hepatitis C–virus (HCV)−viremic kidneys. Serum creatinine values for recipients at each study visit. The clinical course of the recipient who had renal vein thrombosis is show in in Supplementary Figure S1 and is not represented here.

Figure 4

(a) Research and Development (RAND) Corporation 36-Item Short Form Health Survey (SF-36) quality-of-life individual domain scores for recipients of hepatitis C virus (HCV)−viremic kidneys at baseline and 6 months post-transplantation (n = 7). Quality of life was assessed using the SF-36 at the screening and week 12 sustained virologic response (SVR12) visits. Recipient 3, who had renal vein thrombosis and underwent retransplantation, is not represented here. (b) SF-36 quality of life summary scores for recipients of HCV-viremic kidneys at baseline and 6 months post-transplantation (n = 7). Quality of life was assessed using the SF-36 at the screening and week 12 sustained virologic response (SVR12) visits. The SF-36 summary scores are calculated based on the 8 physical and mental domains. Recipient 3, who had renal vein thrombosis and underwent retransplantation, is not represented here.