Managing hepatitis C therapy failures and chronic kidney disease

Area of Science:

• Hepatology
• Infectious Diseases
• Nephrology

Background:

• Hepatitis C virus (HCV) infection causes significant liver and extra-hepatic morbidity, including chronic kidney disease (CKD) and cardiovascular (CV) disease.
• Direct-acting antiviral agents (DAAs) have revolutionized HCV treatment with high efficacy, safety, and short durations.
• Difficult-to-treat populations, such as those with advanced CKD or prior DAA failure, still require effective therapeutic strategies.

Purpose of the Study:

• To review current DAA regimens for treating HCV in challenging patient populations.
• To highlight the efficacy of specific DAA combinations in patients with advanced CKD.
• To discuss treatment options for patients who have previously failed DAA therapy.

Main Methods:

• Review of multicenter phase-3 trials (C-SURFER, EXPEDITION-4) for HCV treatment in advanced CKD.
• Analysis of randomized clinical trials (POLARIS 1-4) for DAA-experienced patients.
• Evaluation of the impact of resistance-associated substitutions (RASs) on DAA treatment outcomes.

Main Results:

• Elbasvir/grazoprevir and glecaprevir/pibrentasvir demonstrated high efficacy in patients with advanced CKD.
• Baseline RASs had minimal impact on treatment outcomes in these CKD patient groups.
• Sofosbuvir/velpatasvir/voxaliprevir is recommended for DAA-naïve patients experiencing treatment failure.

Conclusions:

• Newer DAA regimens are highly effective for HCV in patients with advanced CKD.
• Treatment outcomes for HCV are minimally affected by baseline RASs in advanced CKD.
• Clinicians should consider RAS testing when initiating DAA therapy, especially for DAA-experienced patients.