Managing hepatitis C therapy failures and chronic kidney disease

Expert Rev Clin Pharmacol. 2018 Nov;11(11):1135-1142. doi: 10.1080/17512433.2018.1534202. Epub 2018 Oct 15.

Abstract

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.

Keywords: Chronic kidney disease; DAA failures; direct-acting antivirals; hepatitis C virus.

Publication types

  • Review

MeSH terms

  • Aminoisobutyric Acids
  • Antiviral Agents / administration & dosage*
  • Antiviral Agents / adverse effects
  • Antiviral Agents / pharmacology
  • Benzimidazoles / administration & dosage
  • Benzofurans / administration & dosage
  • Cardiovascular Diseases / physiopathology
  • Cyclopropanes
  • Drug Combinations
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Imidazoles / administration & dosage
  • Lactams, Macrocyclic
  • Leucine / analogs & derivatives
  • Proline / analogs & derivatives
  • Pyrrolidines
  • Quinoxalines / administration & dosage
  • Randomized Controlled Trials as Topic
  • Renal Insufficiency, Chronic / etiology*
  • Renal Insufficiency, Chronic / physiopathology
  • Sulfonamides / administration & dosage
  • Treatment Failure

Substances

  • Aminoisobutyric Acids
  • Antiviral Agents
  • Benzimidazoles
  • Benzofurans
  • Cyclopropanes
  • Drug Combinations
  • Imidazoles
  • Lactams, Macrocyclic
  • Pyrrolidines
  • Quinoxalines
  • Sulfonamides
  • elbasvir-grazoprevir drug combination
  • pibrentasvir
  • Proline
  • Leucine
  • glecaprevir