Retrospective Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 7, 2016; 22(41): 9186-9195
Published online Nov 7, 2016. doi: 10.3748/wjg.v22.i41.9186
Impact of IL28B and OAS gene family polymorphisms on interferon treatment response in Caucasian children chronically infected with hepatitis B virus
Krzysztof Domagalski, Małgorzata Pawłowska, Agnieszka Zaleśna, Małgorzata Pilarczyk, Paweł Rajewski, Waldemar Halota, Andrzej Tretyn
Krzysztof Domagalski, Centre for Modern Interdisciplinary Technologies, Nicolaus Copernicus University, 87-100 Toruń, Poland
Małgorzata Pawłowska, Małgorzata Pilarczyk, Waldemar Halota, Department of Paediatric Infectious Diseases and Hepatology, Faculty of Medicine, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University Torun, 85-030 Bydgoszcz, Poland
Agnieszka Zaleśna, Paweł Rajewski, Provincial Infectious Diseases Hospital in Bydgoszcz, 85-030 Bydgoszcz, Poland
Andrzej Tretyn, Department of Plant Physiology and Biotechnology, Nicolaus Copernicus University, 87-100 Toruń, Poland
Author contributions: Domagalski K and Pawłowska M designed the research; Domagalski K and Zaleśna A performed the research; Zaleśna A, Pilarczyk M and Rajewski P collected the data; Pawłowska M, Halota W and Tretyn A reviewed this article; Domagalski K analysed the data and wrote the paper; and all authors have read and approved the final version to be published.
Institutional review board statement: The study was reviewed and approved by the NCU Bioethics Committee at Collegium Medicum NCU.
Informed consent statement: The patients’ legal guardians and all patients older than 16 signed a written informed consent.
Conflict-of-interest statement: The authors declare that they have no conflicts 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: Małgorzata Pawłowska, MD, PhD, Department of Paediatric Infectious Diseases and Hepatology, Faculty of Medicine, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University Torun, Floriana 12, 85-030 Bydgoszcz, Poland. mpawlowska@cm.umk.pl
Telephone: +48-523-255605 Fax: +48-523-255650
Received: June 27, 2016
Peer-review started: June 27, 2016
First decision: August 8, 2016
Revised: August 31, 2016
Accepted: September 28, 2016
Article in press: September 28, 2016
Published online: November 7, 2016
Abstract
AIM

To investigate the impact of IL28B and OAS gene polymorphisms on interferon treatment responses in children with chronic hepatitis B.

METHODS

We enrolled 52 children (between the ages of 4 and 18) with hepatitis B e antigen-negative chronic hepatitis B (CHB), who were treated with pegylated interferon alfa for 48 wk. Single nucleotide polymorphisms in the OAS1 (rs1131476), OAS2 (rs1293747), OAS3 (rs2072136), OASL (rs10849829) and IL28B (rs12979860, rs12980275 and rs8099917) genes were studied to examine their associations with responses to IFN treatment in paediatric patients. We adopted two criteria for the therapeutic response, achieving an hepatitis B virus (HBV) DNA level < 2000 IU/mL and normalization of ALT activity (< 40 IU/L). To perform the analyses, we compared the patients in terms of achieving a partial response (PR) and a complete response (CR) upon measurement at the 24-wk post-treatment follow-up.

RESULTS

The PR and CR rates were 80.8% and 42.3%, respectively. Factors such as age, gender and liver histology had no impact on the type of response (partial or complete). A statistically significant relationship between higher baseline HBV DNA and ALT activity levels and lower rates of PR and CR was shown (P < 0.05). The allele association analysis revealed that only the IL-28B rs12979860 (C vs T) and IL28B rs12980275 (A vs G) markers significantly affected the achievement of PR (P = 0.021, OR = 3.3, 95%CI: 1.2-9.2 and P = 0.014, OR = 3.7, 95%CI: 1.3-10.1, respectively). However, in the genotype analysis, only IL-28B rs12980275 was significantly associated with PR (AA vs AG-GG, P = 0.014, OR = 10.9, 95%CI: 1.3-93.9). The association analysis for CR showed that the TT genotype of IL28B rs12979860 was present only in the no-CR group (P = 0.033) and the AA genotype of OASL rs10849829 was significantly more frequent in the no-CR group (P = 0.044, OR = 0.26, 95%CI: 0.07-0.88). The haplotype analysis revealed significant associations between PR and CR and OAS haplotype (P = 0.0002 and P = 0.001, respectively), but no association with IL28B haplotype was observed.

CONCLUSION

IL28B and OAS polymorphisms are associated with different clinical outcomes in CHB children treated with interferon.

Keywords: Chronic hepatitis B, IL28B, OAS, Single-nucleotide polymorphisms, IFN therapy, Children

Core tip: The limited efficacy and side effects associated with IFN treatment limit its clinical use in paediatric patients with chronic hepatitis B (CHB). Therefore, pretreatment predictors are required to identify those patients at highest risk for treatment response failure. OAS and IL28B are well-known IFN-induced antiviral pathway players; however, the impact of host-related genetic variability in the IL28B and OAS genes on response rates to IFN therapy in CHB paediatric patients has not been studied. The results of our study show an association between IL28B rs12979860, OASL rs10849829 and OAS haplotypes and final IFN-treatment response in Caucasian CHB children.