Article Text

other Versions

Inhibition of hepatitis C entry: too soon to dismiss while many are still being denied treatment
  1. Susan L Uprichard1,
  2. Bruno Sainz2
  1. 1Department of Medicine, Loyola University Medical Center, Maywood, Illinois, USA
  2. 2Department of Preventative Medicine, Public Health and Microbiology, Autónoma University of Madrid, Madrid, Spain
  1. Correspondence to Dr Susan L Uprichard, Department of Medicine, Loyola University Medical Center, Maywood, IL 60153, USA; suprichard{at}

Statistics from

Recently in Gut, Xiao et al1 detailed an extensive analysis of synergistic inhibition of HCV achieved in various in vitro and in vivo models systems when HCV entry inhibitors were combined with different direct acting antivirals (DAA) and host-targeted antiviral. However, a follow-up commentary by Pawlotsky suggested that ‘there is no unmet clinical need’ for the treatment of HCV that cannot be addressed by the HCV drugs currently approved or in late-stage clinical development.2 Here, we comment on the original study and subsequent commentary.

Consistent with the Xiao et al study, we have reported that blocking the HCV entry factor Neimann-Pick-C1-like-1 (NPC1L1) with the Food and Drug Administration (FDA)-approved drug ezetimibe synergistically inhibits chronic HCV infection in vitro when combined with interferon3 and, as we present in figure 1, with HCV DAAs that block intracellular viral production. Importantly, we also showed that the synergy achieved was dependent on blocking cell-free virus entry as well as blocking HCV cell-to-cell spread.3 While blocking …

View Full Text

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.