Kidney Transplantation From Hepatitis C Virus-Infected Donors to Uninfected Recipients: A Systematic Review for the KDIGO 2022 Hepatitis C Clinical Practice Guideline Update

Abstract

Rationale & objective: Direct-acting antiviral (DAA) treatment of hepatitis C virus (HCV) infection in patients with chronic kidney disease (CKD) has made transplantation of kidneys from HCV-infected donors to uninfected recipients (D+/R-) feasible. To facilitate an update to the 2018 KDIGO guideline for patients with CKD and HCV, we conducted a systematic review of HCV D+/R-kidney transplantation coupled with DAA treatment.

Study design: Systematic review and meta-analysis.

Setting & study populations: We included studies of HCV D+/R-kidney transplantations that used any DAA protocol.

Selection criteria for studies: Based on a search of PubMed, Embase, Cochrane, CINAHL, and ClinicalTrials.gov through February 1, 2022, conferences from 2019 to 2021, and the 2018 KDIGO HCV guideline we identified single-group (D+/R-) or comparative studies of D+/R-versus D-/R-kidney transplantation.

Data extraction: Conducted in SRDR-Plus with review by a second researcher.

Analytical approach: Maximum likelihood meta-analyses; the certainty of evidence was assessed per GRADE (Grading of Recommendations Assessment, Development and Evaluation).

Results: We identified 16 studies (N=557). A sustained viral response at 12 weeks after treatment (SVR12) was observed in 97.7% (95% CI, 96.3%-98.8%). Ultrashort duration treatment (≤8 days) resulted in viremia requiring standard-course DAA treatment in some patients, all of whom achieved SVR12 after 1 or rarely 2 DAA courses. Serious adverse events from DAA treatment were rare after D+/R-transplantation (0.4% [95% CI, 0.1%-2.8%]). At≥1 year after D+/R-transplantation, recipient death occurred in 2.1% (95% CI, 0.9-3.7) and allograft survival was 97.6% (95% CI, 95.7%-98.9%). Estimated glomerular filtration rate 1 year after transplantation ranged from 46 to 74mL/min/1.73m².

Limitations: Analyses were generally based on low-certainty evidence. Uncertainty exists about the long-term safety and efficacy of D+/R-transplantation. Few studies investigated ultrashort treatment courses.

Conclusions: Kidney transplantation from HCV-infected donors to uninfected recipients followed by DAA treatment appears to be safe and associated with excellent 1-year clinical outcomes.

Plain-language summary: Due to the high efficacy of direct-acting antivirals (DAA), the use of kidneys from HCV-infected deceased donors may increase rates of kidney transplantation. We conducted a systematic review for the 2022 KDIGO Clinical Practice Guideline on Hepatitis C to evaluate the safety and efficacy of kidney transplantation from HCV-infected donors to uninfected recipients (D+/R-) followed by DAA therapy. Sixteen studies comprising 557 patients revealed high rates of sustained viral response, low rates of adverse events, and excellent patient and allograft survival 1 year after transplantation. Kidney transplantation from HCV-infected deceased donors to uninfected recipients treated with DAA appears safe and effective. Future studies should investigate shorter treatment durations, monitor safety, and obtain longer-term efficacy data.

Keywords: Chronic kidney disease; direct-acting antivirals; hepatitis C; kidney transplantation systematic review; meta-analysis.