Published online Oct 28, 2018. doi: 10.3748/wjg.v24.i40.4554
Peer-review started: July 27, 2018
First decision: August 27, 2018
Revised: September 2, 2018
Accepted: October 5, 2018
Article in press: October 5, 2018
Published online: October 28, 2018
To investigate how natural killer (NK) cells are affected in the elimination of hepatitis C virus (HCV) by sofosbuvir/ledipasvir, two highly effective direct-acting antivirals (DAAs).
Thirteen treatment-naïve and treatment-experienced chronic hepatitis C (CHC) patients were treated with sofosbuvir/ledipasvir, and NK cells were detected at baseline, weeks 2, 4, 8 and 12 during therapy, and week post of treatment (Pt)-12 and 24 after the end of therapy by multicolor flow cytometry and compared with those from 13 healthy controls.
All patients achieved sustained virological response. There was a significant decline in CD56bright NK cell frequencies at week 8 (P = 0.002) and week 12 (P = 0.003), which were altered to the level comparable to healthy controls at week Pt-12, but no difference was observed in the frequency of CD56dim NK cells. Compared with healthy controls, the expression levels of NKG2A, NKp30 and CD94 on NK cells from CHC patients at baseline were higher. NKG2A, NKp30 and CD94 started to recover at week 12 and reached the levels similar to those of healthy controls at week Pt-12 or Pt-24. Before treatment, patients have higher interferon (IFN)-γ and perforin levels than healthy controls, and IFN-γ started to recover at week 8 and reached the normalized level at week Pt-12.
NK cells of CHC patients can be affected by DAAs, and phenotypes and function of NK cells recover not at early stage but mainly after the end of sofosbuvir/ledipasvir treatment.
Core tip: In our study, we observed the dynamic changes of natural killer (NK) cell subsets, phenotypes and functional parameters during and after direct-acting antivirals (DAAs) treatment and investigated the effect of sofosbuvir/ledipasvir therapy on innate immunity in genotype 1b hepatitis C virus (HCV)-infected patients. We illustrated that NK cells of chronic hepatitis C patients can be affected by DAAs and phenotypes and function of NK cells recovered not at early stage but mainly after the end of sofosbuvir/ledipasvir treatment. These findings may provide an explanation for HCV reinfection or liver carcinogenesis after HCV elimination.