Clinical Trials Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 28, 2018; 24(20): 2191-2202
Published online May 28, 2018. doi: 10.3748/wjg.v24.i20.2191
Regulatory polymorphism of CXCL10 rs1439490 in seronegative occult hepatitis C virus infection
Xu Wang, Song Wang, Zhen-Hua Liu, Wen-Qian Qi, Qian Zhang, Yong-Gui Zhang, De-Rong Sun, Yan Xu, Hong-Guang Wang, Zhong-Xie Li, Xian-Ling Cong, Ping Zhao, Chang-Yu Zhou, Jiang-Bin Wang
Xu Wang, Zhen-Hua Liu, Wen-Qian Qi, Qian Zhang, Yong-Gui Zhang, Yan Xu, Ping Zhao, Chang-Yu Zhou, Jiang-Bin Wang, Department of Digestive, China-Japan Union Hospital Affiliated to Jilin University, Changchun 130033, Jilin Province, China
Song Wang, Department of Urology, First Hospital Affiliated to Jilin University, Changchun 130000, Jilin Province, China
De-Rong Sun, Department of Infectious Disease, the Fourth Affiliated University of Harbin Medical University, Harbin 150001, Heilongjiang Province, China
De-Rong Sun, Department of Digestive, the Second People’s Hospital of Daqing City, Daqing 163461, Heilongjiang Province, China
Hong-Guang Wang, Department of Digestive, People’s Hospital of Jilin City, Changchun 132000, Jilin Province, China
Zhong-Xie Li, Department of Digestive, People’s Hospital of Hunchun City, Hunchun 133300, Jilin Province, China
Xian-Ling Cong, Department of Pathology, China-Japan Union Hospital Affiliated to Jilin University, Changchun 130033, Jilin Province, China
Author contributions: Wang X, Wang S, Liu ZH, Qi WQ and Wang JB designed the study; Wang X, Zhang Q and Wang JB collected and analyzed the data; Cong XL advised on histological staining and analysis; Wang S, Sun DR, Wang HG, Li ZX, Zhao P and Zhou CY contributed to sample collection and intellectual input; Wang X and Wang JB drafted and wrote the manuscript; Wang X, Liu ZH, Qi WQ, Xu Y and Zhang YG revised the manuscript critically for intellectual content; all authors provided intellectual input to the study and approved the final version of the manuscript.
Supported by the National Natural Science Foundation of China, No. 81670533; the Jilin Provincial Science & Technology Department, No. 2013 0102088JC; and the Jilin Provincial Development and Reform Commission, No. 2013C028-3.
Institutional review board statement: This study was approved by the Institutional Review Boards of individual centers. All procedures performed in the studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Clinical trial registration statement: Chinese Clinical Trial Registry (Registration number: ChiCTR-ONRC-12002207). The registration information can be found on the following website: http://www.chictr.org.cn/showproj.aspx?proj=7343
Informed consent statement: Written informed consent was obtained from all individual participants included in the study.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Data sharing statement: No additional data are available.
CONSORT 2010 statement: The authors have read the CONSORT 2010 Statement, and the manuscript was prepared and revised according to the CONSORT 2010 Statement.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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/
Correspondence to: Jiang-Bin Wang, MD, PhD, Professor, Department of Digestive, China-Japan Union Hospital Affiliated to Jilin University, No.126 Xiantai Street, Changchun 130033, Jilin Province, China. zrlwangjb@163.com
Telephone: +86-431-84995303 Fax: +86-431-84641026
Received: February 10, 2018
Peer-review started: February 11, 2018
First decision: March 9, 2018
Revised: March 30, 2018
Accepted: May 11, 2018
Article in press: May 11, 2018
Published online: May 28, 2018
Processing time: 106 Days and 18.6 Hours
Abstract
AIM

To examine the relationship between the single nucleotide polymorphism CXCL10 rs1439490 and seronegative occult hepatitis C virus (HCV) infection (OCI).

METHODS

One hundred and three cases of seronegative OCI and 155 cases of seropositive chronic HCV infection (CHC) were diagnosed at five Liver Centers in Northeastern China, from 2012 to 2016. CXCL10 rs1439490, rs1440802, and IL-28B rs12979860 were analyzed by sequencing. Serum CXCL10 was measured by ELISA. Intrahepatic CXCL10 was determined by quantitative PCR and immunohistochemical semi-quantitative scoring. Liver necroinflammation and fibrosis were scored according to the METAVIR system.

RESULTS

CXCL10 rs1439490 G/G was more prevalent in OCI patients (n = 93/103; 90.3%) than in CHC patients (n = 116/155; 74.8%; P = 0.008). OCI patients had lower serum CXCL10 levels than CHC patients (192.91 ± 46.50 pg/mL vs 354.78 ± 102.91 pg/mL, P < 0.0001). Of IL-28B rs12979860 C/C patients, OCI patients with rs1439490 G/G had lower serum and liver levels of CXCL10 and lower levels of liver necroinflammation and fibrosis than non-G/G patients. OCI patients had higher alanine aminotransferase normalization rates after Peg-interferon treatment than CHC patients (P < 0.05) and serum CXCL10 decreased significantly (P < 0.0001). Liver necroinflammation and fibrosis were alleviated in 8 OCI patients after treatment. Multivariate analysis indicated that rs1439490 G/G significantly influenced the occurrence of OCI in HCV infection (OR = 0.31, 95%CI: 0.15-0.66, P = 0.002).

CONCLUSION

CXCL10 rs1439490 G/G is positively associated with OCI in HCV infection and antiviral outcome.

Keywords: Occult hepatitis C virus infection; CXCL10; Single nucleotide polymorphisms; rs1439490

Core tip: We demonstrated that CXCL10 rs1439490 G/G was more prevalent in patients with seronegative occult hepatitis C virus infection (OCI) than in those with seropositive chronic hepatitis C virus (HCV) infection (CHC). Rs1439490 G/G OCI patients had lower serum and liver levels of CXCL10, and lower levels of liver necroinflammation and fibrosis than non-G/G patients. OCI patients had higher alanine aminotransferase normalization rates after Peg-interferon treatment than CHC patients and serum CXCL10 decreased significantly. We, for the first time, showed that CXCL10 rs1439490 G/G may be positively associated with OCI in HCV infection and antiviral outcome.