One-Year Outcomes of the Multi-Center StudY to Transplant Hepatitis C-InfeCted kidneys (MYTHIC) Trial

Abstract

Introduction: Transplanting kidneys from hepatitis C virus (HCV) viremic donors into HCV-negative patients (HCV D-RNA-positive/R-negative) has evolved from experimental to "standard-of-care" at many centers. Nevertheless, most data derive from single centers and provide only short-term follow-up.

Methods: The Multicenter Study to Transplant Hepatitis C-Infected Kidneys (MYTHIC) study was a multicenter (7 sites) trial of HCV D-RNA-positive/R-negative kidney transplantation (KT) followed by 8 weeks of glecaprevir/pibrentasvir (G/P) initiated 2 to 5 days post-KT. Prespecified outcomes included probability of KT (vs. matched waitlist comparators) and 1-year safety outcomes, allograft function, and survival.

Results: Among 63 enrolled patients, 1-year cumulative incidence of KT was approximately 3.5-fold greater for the MYTHIC cohort versus 2055 matched United Network for Organ Sharing (UNOS) comparators who did not opt-in to receive a kidney from an HCV-viremic donor (68% vs. 19%, P < 0.0001). Of 30 HCV D-RNA-positive/R-negative KT recipients, all achieved HCV cure. None developed clinically significant liver disease or HCV-related kidney injury. Furthermore, 1-year survival was 93% and 1-year graft function was excellent (median creatinine 1.17; interquartile range [IQR]: 1.02-1.38 mg/dl). There were 4 cases of cytomegalovirus (CMV) disease among 10 CMV-negative patients transplanted with a kidney from an HCV-viremic/CMV-positive donor.

Conclusion: The 1-year findings from this multicenter trial suggest that opting-in for HCV-viremic KT offers can increase probability of KT with excellent 1-year outcomes. Trial Registration: NCT03781726.

Keywords: cytomegalovirus infection; direct-acting antivirals; glecaprevir/pibrentasvir; hepatitis C virus; kidney transplantation; organ allocation.

© 2021 International Society of Nephrology. Published by Elsevier Inc.

Figures

Graphical abstract

Figure 1

Cumulative incidence of KT among patients consented for MYTHIC and matched comparators. We time-matched each MYTHIC focal patient, individually, to UNOS comparators who were (as of follow-up time from waitlisting equal to the index MYTHIC patient’s follow-up time at consent) as follows: alive; active on the wait list; equal with respect to race, diabetes status, blood group, obesity (BMI >35 kg/m2), dialysis status at waitlisting (on vs. off); were within 2 years of age; were (at waitlisting) within 1 year of the focal patient’s time on dialysis; were listed at a center quintile based on standardized transplant ratio (intended to reflect the rate of deceased donor transplantation at that center vs. others); and not willing to consider offers from HCV-viremic donors. The time axis in Figure 1 is time since matching, with the time clock reset to 0 at the time of matching. To avoid immortal time bias, each matched UNOS comparator had follow-up time (since waitlisting) equal to that of their respective index MYTHIC patient; that is, as described in the Restriction, Matching, and Statistical Analysis for the Outcome of Time to Transplantation subsection of the Methods section. BMI, body mass index; HCV, hepatitis C virus; KT, kidney transplantation; MYTHIC, Multicenter Study to Transplant Hepatitis C-Infected Kidneys; UNOS, United Network for Organ Sharing.

Figure 2

Hepatitis C antibody status for each HCV-aviremic recipient of a kidney transplant from an HCV-viremic donor, at 4 time points. Heatmap revealing the HCV antibody status of the 30 recipients of HCV-viremic transplants at the following 4 time points: baseline, start of glecaprevir/pibrentasvir treatment (postoperation day 3), week 4 of treatment (1 month after transplant), and 1 year after kidney transplant. Negative HCV antibody is shaded as blue; positive, red; indeterminate, yellow; missing, gray. The antibody status at 1 year was unknown for the 2 patients who died (black). HCV, hepatitis C virus; KT, kidney transplantation; Rx, treatment.

Figure 3

Post-transplant trends in serum creatinine in 30 HCV-negative recipients of HCV-viremic kidneys. HCV, hepatitis C virus.

Figure 4

CMV outcomes among 10 CMV D+/R− recipients of HCV-viremic donor kidneys in MYTHIC. There were 5 cases of clinically significant CMV viremia >1000 IU/ml among CMV D+/R− recipients. The timeline of disease onset and symptoms experienced is illustrated. CMV, cytomegalovirus; D+/R−, donor-positive/recipient-negative; DAA, direct-acting antiviral; GI, gastrointestinal; SVR-12, sustained virologic response at 12 wk.