Efficacy and Safety of Direct-Acting Antivirals in Kidney Transplantation From HCV-Viremic Donors to Negative Recipients: A Meta-Analysis

Frontiers in Medicine. 2022;9:802686
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Background: With the development of direct-acting antiviral agents (DAAs), the research on kidney transplantation from Hepatitis C virus (HCV)-viremic donors to HCV-negative recipients has grown. The objective of this comprehensive analysis was to evaluate the efficacy and safety of DAAs in kidney transplantation from HCV-viremic donors to negative recipients. Methods: Multiple databases were searched for a systematic and comprehensive up to March 2022. The primary outcomes included the percentage of sustained virological response at week 12 after the end of treatment (SVR12), adverse events (AEs; any grade), and severe adverse events (SAEs) as the endpoints. Publication bias was examined by using the funnel plots and Egger's test. Results: In total, 16 studies with 454 subjects were included in the study and the pooled estimate of SVR12, AEs, and SAEs rates were 100.0% (95% CI: 99.2-100.0), 1.9%(95%CI: 0.0-4.9), and 0.0% (95%CI: 0.0-1.5). Subgroup analysis showed that pooled SVR12 rates were 100.0% (95%CI: 99.6-100.0) for genotype (GT)1a and 96.3% (95%CI: 83.3-100.0) for GT2; 100.0% (95%CI: 98.9-100.0) for DAAs treatments; and 100.0% (95%CI: 98.2-100.0) for prophylaxis subgroup. Egger's tests showed that no publication bias was found in this study. Conclusion: This comprehensive analysis showed the high efficacy and safety of DAAs in kidney transplantation from HCV-viremic donors to HCV-negative recipients. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=246541.

CET Conclusion

Reviewer: Mr Simon Knight, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
This systematic review and meta-analysis summarises the literature on the use of direct-acting antivirals (DAAs) in kidney transplant recipients undergoing transplant from a HCV positive donor. The authors identify 16 studies in 454 recipients. Pooled analysis showed a sustained virological response at week 12 of 100%. Rate of adverse events was found to be 1.9%, with no patients experiencing serious adverse events related to DAAs. The authors conclude that DAAs are highly effective and safe for use in this patient population. Methodology appears sound, with a comprehensive search strategy undertaken by 2 reviewers across a number of databases and comprehensive risk of bias assessment undertaken. Studies were all non-randomised or observational in nature, but assessed to have a relatively low risk of bias overall. Given the non-randomised nature of the included studies, use of a fixed-effects analysis is questionable but given the lack of heterogeneity is unlikely to impact the findings significantly.

Study details

Aims : The aim of this study was to assess the efficacy and safety of direct-acting antiviral agents (DAAs) in renal transplantation from hepatitis C virus (HCV) positive donors to HCV negative recipients.
Interventions : Electronic databases including PubMed, Embase, and Web of Science were searched. Study selection and data extraction were performed by two independent reviewers. The Methodological Index for Non-Randomized Studies (MINORS) was used to assess the methodological quality of the included studies.
Participants : 16 studies were included in the meta-analysis.
Outcomes : The primary endpoint was the percentage of sustained virological response at week 12 post-treatment (SVR12). The secondary endpoints included the percentages of HCV transmission from donors to recipients, adverse events, and severe adverse events (SAEs).
Follow up : N/A


Funding : Non-industry funding
Publication type : Systematic Review
Review registration : PROSPERO - CRD42021246541
Organ : Kidney
Language : English
Author email : huangpeng@njmu.edu.cn
MeSH terms : kidney transplantation