Retrospective Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 14, 2020; 26(30): 4479-4488
Published online Aug 14, 2020. doi: 10.3748/wjg.v26.i30.4479
High levels of serum interleukin-6 increase mortality of hepatitis B virus-associated acute-on-chronic liver failure
Chao Zhou, Ning Zhang, Ting-Ting He, Yao Wang, Li-Fu Wang, Yong-Qiang Sun, Jing Jing, Jing-Jing Zhang, Shuang-Nan Fu, Xuan Wang, Xiao-Xiao Liang, Xin Li, Man Gong, Jun Li
Chao Zhou, Ning Zhang, Ting-Ting He, Yao Wang, Li-Fu Wang, Yong-Qiang Sun, Jing Jing, Jing-Jing Zhang, Shuang-Nan Fu, Xuan Wang, Xiao-Xiao Liang, Xin Li, Man Gong, Jun Li, Department of Integrative Medicine, 5th Medical Center of Chinese PLA General Hospital, Beijing 100039, China
Author contributions: Gong M, Li J, and Wang LF conceptualized the study; Zhou C, Zhang N, Sun YQ, Wang Y, and He TT collected the data; Zhou C, Jing J, and Li X performed statistical analysis; Zhang JJ, Wang X, Fu SN, and Liang XX were involved in drafting of the manuscript; all authors revised the manuscript for important intellectual content and approved the final version of the manuscript.
Supported by National Thirteen Five-year Science and Technology Major Project of China, No. 2018ZX10725506-002; and National Twelve Five-year Science and Technology Major Project of China, No. 2012ZX10005-005.
Institutional review board statement: The study was reviewed and approved by the ethics committee of the 302 Military Hospital of China (2012 Aug 22).
Informed consent statement: The need for written informed consent was waived by the ethics committee for this study.
Conflict-of-interest statement: We have no financial relationships to disclose.
Data sharing statement: No additional data are available.
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: Man Gong, MD, Associate Professor, Department of Integrative Medicine, 5th Medical Center of Chinese PLA General Hospital, No. 100 the 4th Ring Road, Beijing 100039, China. gongman302@163.com
Received: April 22, 2020
Peer-review started: April 22, 2020
First decision: June 13, 2020
Revised: June 24, 2020
Accepted: July 16, 2020
Article in press: July 16, 2020
Published online: August 14, 2020
Processing time: 114 Days and 5.3 Hours
ARTICLE HIGHLIGHTS
Research background

Hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF) has a complex and poor prognosis. Interleukin-6 (IL-6) as a pro-inflammatory cytokine is related with severe liver impairment and also plays a role in promoting liver regeneration. Whether serum IL-6 influences HBV-ACLF prognosis has not been studied.

Research motivation

HBV-ACLF is a potentially reversible disease under the condition of intensive care and treatment, therefore, an index used to triage and prognosticate the outcome will promote timely and more appropriate management of the patients.

Research objectives

This study was conducted to determine the impact of serum IL-6 on outcome of patients with HBV-ACLF.

Research methods

We analyzed 412 HBV-ACLF qualified cases from the dataset of National Twelve Five-Year Science and Technology Major Project of China “Study on HBV-ACLF Treated with Integrated Traditional Chinese Medicine and Western Medicine”. The levels of serum IL-6 at baseline and 4 wk were detected and the impact of IL-6 on short-term mortality of patients with HBV-ACLF were analyzed.

Research results

Patients with high IL-6 levels (> 11.8 pg/mL) had a higher mortality within 4 wk than those with low IL-6 levels (≤ 11.8 pg/mL) (24.2% vs 13.2%, P = 0.004; odds ratio [OR] = 2.11, 95% confidence interval [CI]: 1.15-3.90, P = 0.017). The mortality between weeks 5 and 8 in patients with high IL-6 levels at 4 wk was 15.0%, which was significantly higher than the 6.6% mortality rate in patients with low IL-6 levels at 4 wk (hazard ratio = 2.39, 95%CI: 1.05-5.41, P = 0.037). The mortality was 5.0% in patients with high IL-6 levels at baseline and low IL-6 levels at 4 wk, 7.5% in patients with low IL-6 levels both at baseline and at 4 wk, 11.5% in patients with low IL-6 levels at baseline and high IL-6 levels at 4 wk, and 16.7% in patients with high IL-6 levels both at baseline and at 4 wk. The increasing trend of the mortality rate with the dynamic changes of IL-6 was significant (P for trend = 0.023).

Research conclusions

Our study demonstrated that a high level of serum IL-6 increases mortality risk in patients with HBV-ACLF.

Research perspectives

Our results suggest that IL-6 could be a promising candidate to predict mortality in patients with HBV-ACLF, as well as dynamic changes of IL-6. Further prospective studies are required to validate and confirm the predictive value of IL-6.