HCV-Positive Donor Kidneys Safe For Use in HCV-Negative Recipients, Study Finds

Donor hepatitis C virus (HCV) positivity does not negatively impact 1-year rejection and mortality outcomes following renal transplantation in HCV-negative recipients, according to findings from a recent study.1

The retrospective, propensity score-matched case-control study leveraged data from the TriNetX US Collaborative Network and found donor HCV status did not significantly impact post-transplant outcomes, suggesting these organs can be used safely in HCV-negative transplant recipients to expand the donor pool.1

Renal transplantation is considered to be the optimal treatment option for patients with end-stage renal disease, but the demand for transplantation far exceeds the number of donor kidneys available. With this discrepancy projected to grow in coming years, research has focused on ways to expand the donor pool, including transplanting HCV-positive donor kidneys to HCV-negative recipients.1 The advent of direct-acting antivirals (DAAs) has made HCV a much more treatable disease than it was in the era of interferon treatment, with cure rates now exceeding 95%.2

“Currently, data are limited on short-term outcomes related to renal graft rejection in HCV-negative renal transplant recipients who receive a kidney from an HCV-positive donor,” Michael Kueht, MD, an assistant professor of transplant surgery at the University of Texas Medical Branch, and colleagues wrote.1 “Also, there are limited data regarding potential secondary immunologic consequences on common non-HCV viral infections and recipient liver function.”

To address these gaps in research, investigators examined electronic health record data from the TriNetX US Collaborative Network for patients ≥ 18 years of age at the time of their renal transplant between January 2016 and August 2022. Those with any instance of diagnosed transplant status or other organ transplant procedure any time before or up to 1 year after the renal transplant procedure were excluded from the present analysis, as were those with HCV infection or HCV RNA positivity any time prior to transplantation.1

All renal transplant recipients were documented as being HCV-negative at the time of transplant. They were then divided into 2 groups: an experimental cohort representing those who received a renal transplant from an HCV-positive donor (HCV D+/R-) and a control cohort representing those who received a renal transplant from an HCV-negative donor (HCV D-/R-).1

Investigators used 1:1 propensity score matching with greedy nearest neighbor matching and a caliper distance of 0.1 pooled standard deviations of the logit to create balanced cohorts within the database. 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.1

The primary outcome was the 1-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.1

In total, there were 453 HCV D+/R- patients and 23,818 HCV D-/R- patients. After matching, there were 450 patients in each cohort. The mean age at the time of transplant was 57.1 ± 11.9 years, 60% of patients were male, and 38% were African American.1

Upon analysis, the HCV D-/R- cohort had a significantly greater incidence of 1-year rejection (16.6% vs 22.8 %; P = .02) than the HCV D+/R- cohort (hazard ratio [HR], 0.69; 95 % CI, 0.511–0.933). However, in a subanalysis excluding all instances of delayed graft function (n = 822), this difference was no longer apparent (16.3% vs 19.2%; P = .25).1

Of note, no difference was observed for 1-year mortality between the HCV D+/R- and HCV D-/R- cohorts (7.4% vs 6.54%; P = .62). Although mean eGFR was initially significantly increased in the HCV D+/R- cohort, investigators did not observe a difference at 12 months post-transplant (59.1 ± 19.8 vs 55.5 ± 20.2 mL/min; P = 0.08).1

Additionally, investigators did not observe a significant difference in non-HCV virologic outcomes for EBV viremia (2% vs 2.7 %; P = .51); CMV viremia (28.4% vs 23.4%; P = .11); BK viremia (11.7% vs 9.8%; P = .11); or composite non-HCV viremia (11.7% vs 9.80%; P = .1).1

The most common DAA regimen was glecaprevir/pibrentasvir (52.8%). Of the HCV D+/R- patients who had a DAA treatment pathway, 94.65% achieved sustained virologic response 12 weeks after DAA completion.1

“Although allografts from HCV-positive donors are being utilized at more centers, reluctance persists due to concerns over post-transplant outcomes. These data support the continued expansion of the donor pool by utilizing organs from HCV-positive donors for HCV-negative recipients,” investigators concluded.1

References

1. Johnson JC, Engebretsen T, Mujtaba M, et al. Donor hepatitis C status is not associated with an increased risk of acute rejection in kidney transplantation. Surgery in Practice and Science. https://doi.org/10.1016/j.sipas.2024.100236
2. World Health Organization. Hepatitis C. April 9, 2024. Accessed January 24, 2025. https://www.who.int/news-room/fact-sheets/detail/hepatitis-c