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Restoration of natural killer cell activity by interferon‐free direct‐acting antiviral combination therapy in chronic hepatitis C patients
Author(s) -
Nakamura Ikuo,
Furuichi Yoshihiro,
Sugimoto Katsutoshi
Publication year - 2018
Publication title -
hepatology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.123
H-Index - 75
eISSN - 1872-034X
pISSN - 1386-6346
DOI - 10.1111/hepr.13186
Subject(s) - daclatasvir , medicine , ombitasvir , gastroenterology , combination therapy , interferon , ledipasvir , immunology , ribavirin , hepatitis c virus , virus
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 CD56 dim NK and CD56 bright 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 CD56 dim 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 CD56 dim NK cells. Additionally, our results might imply that DAAs therapy could reduce the risk of hepatocarcinogenesis by restoring innate immune responses.