Managing hepatitis C therapy failures and chronic kidney disease.

INTRODUCTION: Hepatitis C virus (HCV) infection leads to important morbidity and mortality through liver disease and extra-hepatic manifestations. Recent evidence suggests the role of HCV in developing chronic kidney disease (CKD); also, HCV adversely affects cardiovascular (CV) disease both in the general population and in patients with CKD. Areas covered: All-oral, interferon-free direct-acting antiviral agents (DAAs) are currently available; anti-HCV regimens based on DAAs are provided with high efficacy and safety and short treatment duration. However, some difficult-to-treat populations still exist including patients with CKD and those who failed previous DAA regimen. Expert commentary: Two DAAs regimens (elbasvir/grazoprevir and glecaprevir/pibrentasvir) are now recommended for the treatment of HCV in patients with advanced CKD, these combinations have shown great efficacy, according to two multicenter phase-3 trials (C-SURFER and EXPEDITION-4). These trials reported a minimal impact of baseline resistance-associated substitutions (RASs) on treatment outcomes. The sofosbuvir/velpatasvir/voxaliprevir combination has been recommended as the first-line option for DAAs failures, on the basis of the results given by two randomized clinical trials involving patients who had been previously received DAA-containing regimens (POLARIS 1-4 studies). It has been suggested that clinicians should consider RASs upon the introduction of DAA-based antiviral therapy.