Observational Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Jun 6, 2020; 8(11): 2255-2265
Published online Jun 6, 2020. doi: 10.12998/wjcc.v8.i11.2255
Cytokines predict virological response in chronic hepatitis B patients receiving peginterferon alfa-2a therapy
Wen-Kang Fu, Jie Cao, Ning-Ning Mi, Chong-Fei Huang, Long Gao, Jin-Duo Zhang, Ping Yue, Bing Bai, Yan-Yan Lin, Wen-Bo Meng
Wen-Kang Fu, Jie Cao, Ning-Ning Mi, Chong-Fei Huang, Long Gao, Wen-Bo Meng, The First Clinical Medical School, Lanzhou University, Lanzhou 730000, Gansu Province, China
Jie Cao, Laboratory Department of the First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
Jin-Duo Zhang, Ping Yue, Bing Bai, Yan-Yan Lin, Wen-Bo Meng, Special Minimally Invasive Surgery Department, The First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
Wen-Bo Meng, Institute of Genetics, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, Gansu Province, China
Wen-Bo Meng, Institute of Hepatopancreatobiliary of Gansu Province, Lanzhou 730000, Gansu Province, Chinao
Wen-Bo Meng, Key Laboratory of Biotherapy and Regenerative Medicine of Gansu Province, Lanzhou 730000, Gansu Province, China
Author contributions: Fu WK and Cao J designed the study and performed the study; Meng WB and Fu WK wrote the manuscript; Fu WK, Huang CF, and Gao L analyzed and interpreted the results; Yue P and Bai B provided intellectual contribution; all authors have reviewed and approved the final manuscript.
Supported by National Natural Science Foundation of China, No. 81872036; Talent Innovation and Entrepreneurship Plan of Chengguan District of Lanzhou City, No. 2019RCCX0038; Science and Technology Plan of Chengguan District of Lanzhou City, No. 2019JSXC0092.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of The First Hospital of Lanzhou University, Lanzhou, China.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: There are no conflicts of interest to report.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE guidelines, and the manuscript was prepared and revised according to the STROBE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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/
Corresponding author: Wen-Bo Meng, MD, PhD, Chief Doctor, Director, Professor, Special Minimally Invasive Surgery Department, The First Hospital of Lanzhou University, No. 1, Donggang West Road, Lanzhou 730000, Gansu Province, China. mengwb@lzu.edu.cn
Received: March 3, 2020
Peer-review started: March 3, 2020
First decision: April 1, 2020
Revised: April 18, 2020
Accepted: April 28, 2020
Article in press: April 28, 2020
Published online: June 6, 2020
Processing time: 96 Days and 16.6 Hours
ARTICLE HIGHLIGHTS
Research background

Hepatitis B virus (HBV) infection remains a global major public health problem. Chronic hepatitis B (CHB) patients generally have an impaired host immune response, which may be associated with persistently high viral load and subsequent T cell failure. Since peginterferon-alpha-2a (PEG-IFN) has direct antiviral and immunoregulatory effects, it has become one of the first choice drugs for the treatment of CHB. PEG-IFN has the properties of immune regulation, and the host immune status may affect the efficacy of PEG-IFN in the treatment of CHB.

Research motivation

Recently, many studies have shown that cytokines and chemokines may play a potential role in chronic viral hepatitis. We aimed to determine the correlation between cytokine/chemokine expression levels and response to PEG-IFN treatment in patients with CHB.

Research objectives

Our main purpose was to analyze the serum levels of cytokines in CHB patients receiving PEG-IFN treatment and responses to the therapy, and to assess the predictive value of the cytokines for the responses to PEG-IFN.

Research methods

In total, 78 serum samples were prospectively collected with written informed consent from 26 CHB patients undergoing PEG-IFN therapy. A Luminex 200 analyzer and Cytokine Array I reagents were used to quantify 46 cytokines in the serum. The serum HBV DNA levels were assayed using a COBAS Amplicor/COBAS TaqMan HBV test, and HBeAb was measured by enzyme immunoassay.

Research results

A total of 26 patients (17 males and 9 females; mean age, 28.8.3 ± 4.161 years in virological responders group, and 27.82 ± 4.446 years in virological non-responders group) were enrolled in the study. The monokine induced by INF-γ (CXCL9) and serum interferon-inducible protein 10 (IP-10) levels at baseline were higher in the virological responders than in the non-virological responders and decreased during treatment. The CXCL9, IP-10, macrophage inflammatory protein 1d (MIP-1d), and thymus and activation-regulated chemokine (TARC) baseline levels exhibited the expected effects for interferon treatment. The area under the receiver operating characteristic curve values of CXCL9, IP-10, MIP-1d, and TARC for predicting the virological response were 0.787, 0.799, 0.787, and 0.77 (P = 0.01, 0.013, 0.01, and 0.021), respectively.

Research conclusions

In conclusion, our results suggest that MIP-1d, CXCL9, CXCL6, IP-10, and TARC have predictive significance in interferon therapy. Cytokines are fundamental molecules in the complex signaling network of cell-mediated immunity. Analyses of the changes in cytokine expression patterns during treatment can help to understand the pathogenesis of CHB and predict treatment responses.

Research perspectives

Further large and long-term follow-up studies are required to determine the predictive value of cytokines in CHB patients receiving PEG-IFN treatment. Besides, the differences in these factors between the response and non-response groups and their specific biological roles in HBV infection require further investigation.