Retrospective Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 28, 2016; 22(44): 9813-9821
Published online Nov 28, 2016. doi: 10.3748/wjg.v22.i44.9813
IFIT1 polymorphisms predict interferon-α treatment efficiency for hepatitis B virus infection
Dong-Ying Xie, Shi-Ming Wang, Jing-Min Yang, Liang-Hui Wang, Hong-Yan Chen, Cong Huai, Jia Shang, Qing Mao, Chun-Liang Lei, Guang-Han Luo, Ji Qian, Da-Ru Lu
Dong-Ying Xie, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510000, Guangdong Province, China
Shi-Ming Wang, Jing-Min Yang, Liang-Hui Wang, Hong-Yan Chen, Cong Huai, Ji Qian, Da-Ru Lu, State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200438, China
Jia Shang, Henan Provincial People’s Hospital, Zhengzhou 450000, Henan Province, China
Qing Mao, The First Affiliated Hospital of Third Military Medical University, Chongqing 404100, China
Chun-Liang Lei, The Eighth People’s Hospital of Guangzhou, Guangzhou 510000, Guangdong Province, China
Guang-Han Luo, The First Affiliated Hospital of Guangxi Medical University, Nanning 530000, Guangxi Zhuang Autonomous Region, China
Author contributions: Xie DY and Wang SM contributed equally to this work; Xie DY, Wang SM and Yang JM conceived and designed the study; Lu DR designed and supervised the study; Wang SM analyzed the data and drafted the manuscript; Wang SM, Yang JM and Wang LH conducted the experiments and interpreted the data; Xie DY, Shang J, Mao Q, Lei CL and Luo GH collected the patients and offered material supports; Chen HY, Huai C and Qian J provided analytical oversight and revision suggestions; all authors have read and approved the final version to be published.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University.
Informed consent statement: All study participants provided informed written consent prior to study enrollment.
Conflict-of-interest statement: All authors declare no conflict of interest.
Data sharing statement: No additional data are available.
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: Da-Ru Lu, PhD, Professor, State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, Institute of Genetics, School of Life Sciences, Fudan University, Life Science Building, Jiangwan Campus of Fudan University, No. 2005 Songhu Road, Shanghai 200438, China. darulu@hotmail.com
Telephone: +86-21-51630619 Fax: +86-21-51630619
Received: June 24, 2016
Peer-review started: June 24, 2016
First decision: July 29, 2016
Revised: August 19, 2016
Accepted: September 8, 2016
Article in press: September 8, 2016
Published online: November 28, 2016
Processing time: 155 Days and 8.8 Hours
Abstract
AIM

To investigate the association between interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) polymorphisms and interferon-α (IFNα) treatment efficiency among Chinese hepatitis B virus (HBV) infection patients.

METHODS

Two hundred and twenty five newly diagnosed chronic hepatitis B (CHB) patients were enrolled in the study. All of these patients received IFNα treatment for a course of 48 wk, and were followed up for 24 wk after the treatment was end. Clinical information about virological response, hepatitis B e antigen (HBeAg) seroconversion rate and combined response at the end of the treatment, as well as the sustained response by the time of following up 24 wk after the treatment, was collected. Four tag-single nucleotide polymorphisms (SNPs) of IFIT1 were selected and assessed for their association with these clinical outcomes.

RESULTS

At the end of the treatment, HBeAg seroconversion was observed in 27.1% patients. Thirty-six point nine percent patients achieved virological response, and 15.6% patients exhibited combined response. Sustained response was obtained in 26.2% patients. The main HBV genotype of the study was genotype B. Patients who infected with HBV genotype B or C showed better treatment efficiency, no matter which clinical outcome was considered. Among the four SNPs assessed, rs303218 (A > G) was found to be significantly associated with the end point virological response when assuming additive model [OR = 0.64 (95%CI: 0.42-0.96), P = 0.032]. Patients who carried rs303218 GG genotype had a rather higher rate of achieving virological response (response rate: 52%, OR = 0.40, 95%CI: 0.18-0.91; P = 0.028) when compared to those had AA genotype (response rate: 27%). The most significant interaction was observed in patients who had relative lower baseline aspartate transaminase. No association between SNPs and HBeAg seroconversion, combined response or sustained response was observed.

CONCLUSION

IFIT1 involves in the regulation of IFNα treatment for CHB and its polymorphism rs303218 can predict the end point virological response. The finding requires further validation.

Keywords: Virological response; Hepatitis B virus infection; IFIT1; Interferon-α therapy; Polymorphism

Core tip: Interferon-α (IFNα) is the first line treatment for chronic hepatitis B virus (HBV) infection (CHB). However, its efficiency differs and biomarkers for predicting responses of IFNα are needed. The current study performed an epidemiologic study to investigate the association between Interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) polymorphisms and clinical responses of IFNα treatment in newly diagnosed chronic HBV infection patients among Chinese population. We identified that IFIT1 polymorphism rs303218 could be a predictor for the end point virological response of IFNα therapy. The finding may provide insight to the potential role of IFIT1 in the individualized treatment of CHB in the future.