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©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
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
BACKGROUND
Chronic hepatitis B virus infection remains a major global public health problem. Peginterferon-alpha-2a (PEG-IFN) has direct antiviral and immunoregulatory effects, and it has become one of the first choice drugs for the treatment of chronic hepatitis B (CHB). Cytokines play an important role in immunity, and they directly inhibit viral replication and indirectly determine the predominant pattern of the host immune response.
AIM
To determine the correlation between cytokine/chemokine expression levels and response to PEG-IFN treatment in patients with CHB.
METHODS
Forty-six kinds of cytokines were analyzed before PEG-IFN therapy and at 24 wk during therapy in 26 CHB patients.
RESULTS
The monokine induced by INF-γ (CXCL9) and serum interferon-inducible protein 10 ( IP-10) levels at baseline were higher in virological responders than in non-virological responders (NRs) and decreased during treatment, whereas the NRs did not exhibit significant changes. The macrophage inflammatory protein 1d (MIP-1d) levels at baseline and during treatment were significantly higher in the virological responders than in the NRs, while thymus and activation-regulated chemokine (TARC) levels at baseline and during treatment were significantly lower in the virological responders than in the NRs. The CXCL9, IP-10, MIP-1d, and 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 virological responses were 0.787, 0.799, 0.787, and 0.77 (P = 0.01, 0.013, 0.01, and 0.021), respectively.
CONCLUSION
We found that cytokine levels before and during treatment may represent potential biomarkers to select CHB patients who can respond to PEG-IFN. Therefore, cytokines can be used as an indicator of antiviral drug selection before CHB treatment.
Core tip: Analyses of the changes in cytokine expression patterns during treatment can help to understand the pathogenesis of chronic hepatitis B and predict treatment responses. We found that macrophage inflammatory protein 1d, CXCL9, CXCL6, interferon-inducible protein 10, and thymus and activation-regulated chemokine have predictive significance in interferon therapy. Therefore, further large and long-term follow-up studies are needed to determine the predictive value of cytokines in chronic hepatitis B patients receiving peginterferon-alpha-2a treatment. In addition, the differences in these factors between the response and non-response groups and their specific biological roles in hepatitis B virus infection require further investigation.
