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©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
Analysis of the effects of donor and recipient hepatitis C infection on kidney transplant outcomes in the United States
Qing Yuan, Shanjuan Hong, Gregory Leya, Eve Roth, Georgios Tsoulfas, WW Williams, Joren C Madsen, Nahel Elias
Qing Yuan, Department of Urology, Chinese PLA General Hospital, Beijing 100853, China
Qing Yuan, Shanjuan Hong, Gregory Leya, Eve Roth, WW Williams, Joren C Madsen, Nahel Elias, Transplant Center and Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA 02114, United States
Georgios Tsoulfas, Department of Surgery, Aristototle University of Thessaloniki, Thessaloniki 541 24, Greece
WW Williams, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, United States
Joren C Madsen, Division of Cardiac Surgery, Massachusetts General Hospital, Boston, MA 02114, United States
Nahel Elias, Division of Transplant Surgery, Massachusetts General Hospital, Boston, MA 02114, United States
Author contributions: Yuan Q and Elias N contributed to study conception and design; Acquisition of data: Elias N contributed to analysis and interpretation of data; Yuan Q, Hong S, Leya G, Roth E, Tsoulfas G, Williams WW and Elias N contributed to analysis and interpretation of data; Yuan Q, Hong S, Leya G, Roth E, Tsoulfas G, Williams WW and Elias N contributed to drafting of manuscript; all authors have read and approve the final manuscript.
Institutional review board statement: The above referenced project does not meet the criteria for human subject research as defined by Mass General Brigham Human Research Office policies and Health and Human Services regulations set forth in 45 CFR 46. Based on the information you provided this activity is not human subjects research because it does not involve human subjects. The project does not require IRB approval.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Nahel Elias, MD, Assistant Professor, Surgeon, Transplant Center and Center for Transplantation Sciences, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, United States. elias.nahel@mgh.harvard.edu
Received: September 21, 2022
Peer-review started: September 21, 2022
First decision: October 24, 2022
Revised: November 7, 2022
Accepted: December 21, 2022
Article in press: December 21, 2022
Published online: February 18, 2023
ARTICLE HIGHLIGHTS
Research background
While Hepatitis C virus infection (HCV+) kidneys have traditionally been discarded rather than transplanted into HCV- recipients, the introduction of direct-acting antivirals (DAAs) in 2013 revolutionized HCV treatment by consistently achieving sustained virologic responses, opening the door for transplantation of HCV+ organs.
Research motivation
As HCV+ rates in kidney donors and transplant recipients rise, the introduction of DAA may effect transplant outcomes.
Research objectives
To analyze the effects of HCV+ in donors, recipients, or both, on deceased-donor (DD) kidney transplantation (KT) outcomes, and the impact of DAAs on those effects.
Research methods
The Organ Procurement and Transplantation Network data of adult first solitary DD-KT recipients 1994-2019 were allocated into four groups by donor and recipient HCV+ status. We performed patient survival (PS) and death-censored graft survival (DCGS) pairwise comparisons after propensity score matching to assess the effects of HCV+ in donors and/or recipients, stratifying our study by DAA era to evaluate potential effect modification.
Research results
Pre-DAA, for HCV+ recipients, receiving an HCV+ kidney was associated with 1.28-fold higher mortality (HR 1.151.281.42) and 1.22-fold higher death-censored graft failure (HR 1.081.221.39) compared to receiving an HCV- kidney and the absolute risk difference was 3.3% (95%CI: 1.8%-4.7%) for PS and 3.1% (95%CI: 1.2%-5%) for DCGS at 3 years. The HCV dual-infection (donor plus recipient) group had worse PS (0.56-fold) and DCGS (0.71-fold) than the dual-uninfected. Donor HCV+ derived worse post-transplant outcomes than recipient HCV+ (PS 0.36-fold, DCGS 0.34-fold). In the DAA era, the risk associated with HCV+ in donors and/or recipients was no longer statistically significant, except for impaired PS in the dual-infected vs dual-uninfected (0.43-fold).
Research conclusions
Prior to DAA introduction, donor HCV+ negatively influenced kidney transplant outcomes in all recipients, while recipient infection only relatively impaired outcomes for uninfected donors. These adverse effects disappeared with the introduction of DAA.
Research perspectives
Given comparable outcomes across all four patient cohorts in the DAA era, a new allocation algorithm, eliminating HCV+ kidneys’ negative influence on the KDRI, is urgently needed to improve utilization and allocation of this under-utilized resource.
