A Systematic Review of Direct-Acting Antivirals for Hepatitis C in Advanced CKD

Ethan M Balk; Gaelen P Adam; Michel Jadoul; Paul Martin; Craig E Gordon

doi:10.1016/j.ekir.2022.11.008

A Systematic Review of Direct-Acting Antivirals for Hepatitis C in Advanced CKD

Kidney Int Rep. 2022 Dec 1;8(2):240-253. doi: 10.1016/j.ekir.2022.11.008. eCollection 2023 Feb.

Authors

Ethan M Balk¹, Gaelen P Adam¹, Michel Jadoul², Paul Martin³, Craig E Gordon⁴

Affiliations

¹ Brown Center for Evidence Synthesis in Health, Brown School of Public Health, Brown University, Providence, Rhode Island, USA.
² Department of Nephrology, Cliniques universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium.
³ Division of Digestive Health and Liver Diseases, University of Miami School of Medicine, Miami, Florida, USA.
⁴ Division of Nephrology, Department of Medicine, Tufts University School of Medicine, Boston, Massachussetts, USA.

Abstract

Introduction: Direct-acting antivirals (DAAs) have improved treatment of hepatitis C virus (HCV) infection in patients with chronic kidney disease (CKD). To facilitate the 2022 update of the Kidney Disease: Improving Global Outcomes (KDIGO) guideline for CKD patients with HCV, we systematically reviewed DAA regimens in patients with CKD stages G4 and G5 nondialysis (G4-G5ND), CKD stage G5 on dialysis (G5D), and kidney transplant recipients (KTRs).

Methods: We conducted a systematic review by searching PubMed, Embase, Cochrane, CINAHL, and ClinicalTrials.gov through February 1, 2022, and conferences from 2019 to 2021. Studies of HCV-infected patients with CKD G4-G5ND, G5D, and KTRs treated with specified DAA regimens were included. Outcomes included death at 6 months or later, sustained virologic response at 12 weeks (SVR12), serious adverse events (SAEs) attributed to DAA, and treatment discontinuation because of adverse events. Maximum likelihood meta-analyses were determined; certainty of evidence was assessed per GRADE (Grading of Recommendations Assessment, Development, and Evaluation).

Results: We identified 106 eligible studies (22 reported on CKD G4-G5ND, 69 on CKD G5D, and 29 on KTRs). In each population, the majority of DAA regimens achieved SVR12 ≥ 93%. We found generally low quality of evidence of low risk of SAEs (mostly 0%, up to 2.9%) and low risk of discontinuation because of adverse events (mostly 0%-5%). Across 3 unadjusted observational studies in KTRs, the risk of death after DAA treatment was substantially lower than without treatment (summary odds ratio, 0.16; 95% CI, 0.04-0.61).

Conclusion: Combination DAA regimens are safe and highly effective in patients with advanced CKD, on dialysis, and with kidney transplants.

Keywords: chronic kidney disease; dialysis; direct-acting antivirals; hepatitis C; kidney transplant recipient; systematic review.