Donor hepatitis C status is not associated with an increased risk of acute rejection in kidney transplantation

Abstract

Introduction: In renal transplantation, donor hepatitis C virus (HCV) status is crucial to consider when selecting a recipient given the high likelihood of transmission. We analyzed the effect of donor HCV status on post-renal transplant rejection and virologic infectious outcomes using electronic health record data from multiple US health care organizations.

Methods: Using real world data from electronic health records of renal transplant recipients, a propensity score-matched case-control study of one-year renal transplant outcomes was conducted on cohorts of HCV-negative recipients who received an organ from an HCV-positive donor (HCV D+/R-) versus from an HCV-negative donor (HCV D-/R-). Donor HCV positivity was defined as new recipient HCV positivity within 30 days post-transplant. Cohorts were matched by major risk factors for rejection including age, gender, race, etiologies of end-stage renal disease, dialysis dependence, donor type, induction immunosuppression, and virologic lab studies. The primary outcome was one-year incidence of rejection. Secondary outcomes included longitudinal measures of liver and kidney function, incidence of non-HCV viremia, and DAA treatment pathways and responses.

Results: Data from 900 renal transplant recipients were analyzed, 450 subjects per group (D+/R-, D-/R-). Mean age at transplant was 57.1 ± 11.9 years, 60 % were male, and 38 % were African American. Kaplan-Meier analysis showed a significantly increased incidence of one-year rejection for HCV D-/R- compared to HCV D+/R- (16.6% vs 22.8 %, p = 0.02). This difference did not persist on a sub-analysis excluding subjects with delayed graft function (DGF) (16.3% vs 19.2 %, p = 0.25). Although mean eGFR was initially higher in HCV D+/R-, there were no significant differences in liver or kidney allograft function at 12 months. There was no significant difference for composite viremia (CMV/EBV/BK; 37.66% vs 31.60 %, p = 0.07). The most common DAA regimen was glecaprevir/pibrentasvir (52.8 %). DAA treatment responses were excellent, with most subjects having a negative viral load by 90 days (mean: 1.7 ± 1.9 log units/mL).

Conclusion: Donor HCV positivity did not negatively impact one-year rejection outcomes post-renal transplantation. Importantly, this effect was not biased by age. Anti-HCV treatment was effective and liver and kidney function were excellent at one-year post-transplant. These data support the continued expansion of the donor pool by utilizing organs from HCV-positive donors in the era of anti-HCV direct-acting antiviral therapies.

Keywords: BK virus; Cytomegalovirus; Epstein-Barr virus; Hepatitis C; Kidney; Rejection.

Fig. 1

Cohort flow diagram. Outline of how cohorts were established and how many patients were included or excluded in each cohort based on specified inclusion/exclusion criteria.

Fig. 2

DAA Treatment diagram. Direct-acting antiviral treatment pathways for the HCV D+/R- cohort captured from the EMR from the same day to 365 days post-renal transplant procedure. N = 158 (52.8 %) patients received a combination of Glecaprevir/Pibrentasvir (111.2 ± 43.2 days on treatment; n = 17 patients had a medication switch), n = 124 (41.8 %) patients received a combination of Sofosbuvir/Velpatasvir (116.8 ± 40.2 days on treatment; n = 4 patients had a medication switch), followed by Elbasvir/Graxoprevir (2.7 %), and Sofosbuvir/Ledipasvir (2.0 %). 154 patients did not have a recorded instance of DAA treatment in their EMR.

Fig. 3

Rejection and viremia one-year post-transplant. (A) Cumulative incidence curve of 1-year renal transplant rejection between HCV D+/R- and HCV D-/R- cohorts. The HCV D-/R- had significantly higher 1-year incidences of renal transplant rejection (16.60% vs 22.82 %, p = 0.02). (B) Cumulative incidence curve of 1-year composite viremia (EBV, CMV, and BK viremia). No significant difference was found between the HCV D+/R- and HCV D-/R- for 1-year incidences of composite viremia (37.66% vs 31.60 %, p = 0.07). (C) Cumulative incidence curve of 1-year EBV viremia. No significant difference was found between the HCV D+/R- and HCV D-/R- for 1-year incidences of EBV viremia (2.03% vs 2.74 %, p = 0.51). (D) Cumulative incidence curve of 1-year CMV viremia. No significant difference was found between the HCV D+/R- and HCV D-/R- for 1-year incidences of CMV viremia (28.43% vs 23.44 %, p = 0.11). (E) Cumulative incidence curve showing no significant difference between the HCV D+/R- and HCV D-/R- cohorts for 1-year incidences of BK viremia (11.67% vs 9.80%, p = 0.11).