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

Area of Science:

• Nephrology
• Hepatology
• Pharmacology

Background:

• Direct-acting antivirals (DAAs) have transformed hepatitis C virus (HCV) treatment.
• Patients with chronic kidney disease (CKD) present unique challenges for HCV management.
• Evidence for DAA efficacy and safety in advanced CKD stages is crucial for guideline updates.

Purpose of the Study:

• To systematically review direct-acting antiviral (DAA) regimens for hepatitis C virus (HCV) infection.
• To evaluate DAA effectiveness and safety in patients with advanced CKD (stages G4-G5 nondialysis, G5 dialysis) and kidney transplant recipients (KTRs).
• To inform the 2022 Kidney Disease: Improving Global Outcomes (KDIGO) guideline update.

Main Methods:

• Systematic literature review of studies published up to February 1, 2022, and conference abstracts from 2019-2021.
• Included studies focused on HCV-infected patients with CKD G4-G5ND, G5D, and KTRs treated with DAAs.
• Outcomes assessed included sustained virologic response (SVR12), serious adverse events (SAEs), treatment discontinuation, and mortality.

Main Results:

• Over 106 studies were reviewed, covering CKD G4-G5ND, G5D, and KTR populations.
• The majority of DAA regimens achieved high SVR12 rates (≥93%) across all patient groups.
• Evidence indicated a low risk of SAEs and treatment discontinuation due to adverse events, with significantly lower mortality risk observed in KTRs treated with DAAs.

Conclusions:

• Combination DAA regimens demonstrate high efficacy in achieving sustained virologic response in patients with advanced CKD, on dialysis, and post-kidney transplant.
• DAA therapy is generally safe in these complex patient populations, with a low incidence of serious adverse events and treatment discontinuations.
• DAA treatment is associated with reduced mortality risk, particularly in kidney transplant recipients.