• ANTIVIRAL THERAPY
• HEPATITIS C

Recently in Gut, Xiao et al 1 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 …