Basic Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 14, 2016; 22(18): 4529-4537
Published online May 14, 2016. doi: 10.3748/wjg.v22.i18.4529
Elevated serum interleukin-38 level at baseline predicts virological response in telbivudine-treated patients with chronic hepatitis B
Hong-Juan Wang, Yan-Fang Jiang, Xin-Rui Wang, Man-Li Zhang, Pu-Jun Gao
Hong-Juan Wang, Xin-Rui Wang, Pu-Jun Gao, Department of Hepatology, First Hospital of Jilin University, Changchun 130021, Jilin Province, China
Hong-Juan Wang, Yan-Fang Jiang, Xin-Rui Wang, Man-Li Zhang, Department of Central Laboratory, the Second Part of First Hospital of Jilin University, Changchun 130021, Jilin Province, China
Yan-Fang Jiang, Key Laboratory of Zoonosis Research, Ministry of Education, Jilin University, Changchun 130021, Jilin Province, China
Man-Li Zhang, Department of Hepatology and Gastroenterology, the Second Part of First Hospital of Jilin University, Changchun 130021, Jilin Province, China
Author contributions: Wang HJ, Jiang YF and Gao PJ contributed equally to this work; Jiang YF, Gao PJ and Wang HJ designed the research; Wang HJ, Wang XR and Zhang ML performed the research; Wang HJ, Jiang YF and Gao PJ analyzed the data and wrote the paper.
Institutional review board statement: The study was reviewed and approved by the First Hospital of Jilin University Institutional Review Board.
Conflict-of-interest statement: The authors declare no financial or commercial 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: Pu-Jun Gao, MD, PhD, Department of Hepatology, First Hospital of Jilin University, 71 Xinmin Street, Changchun 130021, Jilin Province, China. pujun-gao@163.com
Telephone: +86-431-88785116 Fax: +86-431-84808391
Received: December 26, 2015
Peer-review started: December 28, 2015
First decision: January 13, 2016
Revised: February 3, 2016
Accepted: March 1, 2016
Article in press: March 2, 2016
Published online: May 14, 2016
Processing time: 130 Days and 7.9 Hours
Abstract

AIM: To investigate serum interleukin (IL)-38 level and its clinical role in predicting virological response (VR) to telbivudine (LdT) in patients with chronic hepatitis B (CHB).

METHODS: The study participants were divided into two groups; one group consisted of 43 healthy controls (HCs) and the other group consisted of 46 patients with hepatitis B e antigen-positive CHB. All patients were administered 600 mg of oral LdT daily for 52 wk, and they visited physicians every 12 wk for physical examination and laboratory tests. Serum IL-38 levels were determined using ELISA. The concentrations of serum Th1- and Th2-type cytokines were measured using the cytometric bead array (CBA) method.

RESULTS: Serum levels of IL-38 at baseline in all patients were higher than those in HCs [306.97 (123.26-492.79) pg/mL vs 184.50 (135.56-292.16) pg/mL, P = 0.019]; the levels returned to normal after the first 12 wk of treatment with LdT [175.51 (103.90-331.91) pg/mL vs 184.50 (135.56-292.16) pg/mL, P > 0.05]. Serum IL-38 levels at baseline were positively associated with serum aspartate aminotransferase levels in patients with CHB (r = 0.311, P = 0.036). Higher levels of serum IL-38 at baseline were associated with a greater probability of VR to LdT treatment at 24 wk (48.15% vs 15.79%, P = 0.023) and 52 wk (66.67% vs 36.84%, P = 0.044). The levels of serum IL-38 in patients with primary non-response at week 12 after treatment initiation were lower than those in patients with primary response [64.44 (49.85-172.08) pg/mL vs 190.54 (121.35-355.28) pg/mL, P = 0.036]. Serum IL-38 levels were correlated with serum IL-6 and IL-12 levels in patients with CHB during treatment with LdT.

CONCLUSION: Elevated serum IL-38 levels in untreated CHB patients reflect ongoing liver injury. Higher serum IL-38 levels before treatment indicate a greater probability of VR to LdT treatment.

Keywords: Alanine aminotransferase; Aspartate aminotransferase; Interleukin-6; Interleukin-12; Interleukin-38; Chronic hepatitis B; Primary non-response; Virological response

Core tip: This is the first study detailing kinetic changes in serum interleukin-38 (IL-38) levels during chronic hepatitis B (CHB). Higher pretreatment serum IL-38 levels are associated with a greater probability of virological response to telbivudine treatment. Elevated levels of serum IL-38 in untreated patients with CHB reflect ongoing liver injury, which is an indirect indicator of vigorous endogenous clearance of hepatitis B virus infection. Our findings suggest that clear signs of viral clearance at baseline may predict a favorable response to treatment of CHB using nucleoside analogs.