古市　好宏
   Department   School of Medicine(Tokyo Women's Medical University Adachi Medical Center), School of Medicine
   Position   Associate Professor
Article types Original article
Language English
Peer review Peer reviewed
Title Restoration of natural killer cell activity by interferon-free direct-acting antiviral combination therapy in chronic hepatitis C patients.
Journal Formal name：Hepatology research : the official journal of the Japan Society of Hepatology
Abbreviation：Hepatol Res
ISSN code：13866346/13866346
Domestic / ForeginForegin
Volume, Issue, Page 48(11),pp.855-861
Author and coauthor Nakamura Ikuo, Furuichi Yoshihiro, Sugimoto Katsutoshi
Publication date 2018/10
Summary AIM:Interferon-free direct-acting antiviral (DAA) therapy is an effective treatment for chronic hepatitis C (CH(C)) patients. Activity of natural killer (NK) cells was reported to be impaired in patients with hepatitis C virus infection. The aim of this study was to examine whether DAA therapy could restore NK activity in patients with CH(C).METHODS:Direct-acting antiviral therapy was given to 31 CH(C) patients as asunaprevir/daclatasvir (ASV/DCV) (n = 15), ledipasvir/sofosbuvir (n = 7), ombitasvir/paritaprevir/ritonavir (n = 6), or elbasvir/grazoprevir (n = 3). Prior to therapy (0M), at the completion of the therapy (EOT), and at 24 weeks after completion (AFTER), NK activity and the frequency of CD56dim NK and CD56bright NK cells in peripheral blood were estimated by Cr release assay and flow cytometry. Statistical analysis was carried out by anova and the Mann-Whitney U-test.RESULTS:In one of the ASV/DCV-treated patients, treatment was stopped 12 weeks after initiation of therapy because of viral breakthrough. The anova showed that NK activity significantly improved at EOT (vs. 0M, P < 0.01) and at AFTER (vs. 0M, P < 0.001) in 30 patients with sustained virologic response. It also showed that the frequency of CD56dim NK cells was significantly increased at EOT and at AFTER (vs. 0M, P < 0.05). In addition, the NK activity ratio (AFTER/0M) had no significant difference between patient groups with higher and lower Fibrosis-4 scores.CONCLUSION:Direct-acting antiviral therapy in CH(C) patients could improve NK activity by increasing the frequency of CD56dim NK cells. Additionally, our results might imply that DAAs therapy could reduce the risk of hepatocarcinogenesis by restoring innate immune responses.
DOI 10.1111/hepr.13186
PMID 29732688