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