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Sci Rep. 2017 Jul 19;7(1):5866. doi: 10.1038/s41598-017-06192-1.

A Practical Model Evaluating Antiviral Cytokines by Natural Killer Cells in Treatment Naïve Patients with Chronic Hepatitis B Virus Infection.

Li X1, Gu Y1, Guo X2,3,4, Gu L5, Zhou L1, Wu X1, Wang X2,3,6, Stamataki Z7, Huang Y8,9.

Author information

1
Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
2
Department of Statistical Science, School of Mathematics, Sun Yat-Sen University, Guangzhou, China.
3
Southern China Center for Statistical Science, Sun Yat-Sen University, Guangzhou, China.
4
Department of Ophthalmology, University of Melbourne, Melbourne, Australia.
5
Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
6
Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
7
Institute for Immunology and Immunotherapy and NIHR Biomedical Research Centre, University of Birmingham, Birmingham, United Kingdom.
8
Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. huangyh53@mail.sysu.edu.cn.
9
Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. huangyh53@mail.sysu.edu.cn.

Abstract

Natural killer (NK) cells play a major role in anti-viral immunity as first line defense during hepatitis B infection, particularly in untreated patients whose T cells functions are profoundly impaired. Cytokine interferon (IFN)-γ and tumor necrosis factor (TNF)-α produced by NK cells are important anti-viral factors. However, there is lack of a quantifiable model to evaluate cytokine responses by NK cells. In this study, almost half of the patients (47.9%) beyond treatment criteria had high cytokine activity, although it was lower than those recommended for antiviral therapy (78.2%). Moreover, we developed a model that low levels of HBsAg, HBcAb, and albumin and high fibrosis values predicted strong antiviral cytokine production by NK cells. Based on the cut-off score (0.361) obtained from the multivariable model, patients with 67%, 8%, 92%, and 74% in immune-active (IA), immune-tolerant (IT), immune-inactive (IC), and grey zone (GZ), respectively, showed active antiviral cytokines produced by NK cells. These results suggest that those who possess activated cytokine responses beyond the current treatment criteria may have potential implications for the timing of antiviral therapy to achieve better virus control.

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