Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 28, 2018; 24(40): 4554-4564
Published online Oct 28, 2018. doi: 10.3748/wjg.v24.i40.4554
Recovery of natural killer cells is mainly in post-treatment period in chronic hepatitis C patients treated with sofosbuvir plus ledipasvir
Xiao-Xiao Wang, Bi-Fen Luo, Han-Ji Jiang, Xu Cong, Qian Jin, Dan-Li Ma, Lai Wei, Bo Feng
Xiao-Xiao Wang, Bi-Fen Luo, Han-Ji Jiang, Xu Cong, Qian Jin, Dan-Li Ma, Lai Wei, Bo Feng, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Peking University People’s Hospital, Beijing 100044, China
Author contributions: Wang XX, Luo BF, Wei L and Feng B designed the study, performed data analysis, and wrote and edited the manuscript; Luo BF, Jiang HJ, Jin Q and Ma DL enrolled the patients; Wang XX, Jiang HJ, and Cong X performed sample testing; all authors reviewed and approved the manuscript.
Supported by the National S&T Major Projects for Infectious Diseases Control, No. 2017ZX10302201-004-001.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of Peking University People’s Hospital.
Conflict-of-interest statement: To the best of our knowledge, no conflict of interest exists.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Bo Feng, PhD, Chief Doctor, Professor, Research Fellow, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Peking University People’s Hospital, No. 11, Xizhimen South Street, Beijing 100044, China. fengbo@pkuph.edu.cn
Telephone: +86-10-88325980 Fax: +86-10-66515490
Received: July 27, 2018
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
Abstract
AIM

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).

METHODS

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.

RESULTS

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.

CONCLUSION

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.

Keywords: Direct-acting antivirals therapy, Hepatitis C virus, Natural killer cells, Natural killer subsets

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.