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
Abstract
BACKGROUND

Patients with hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF) present a complex and poor prognosis. Systemic inflammation plays an important role in its pathogenesis, and 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.

AIM

To determine the impact of serum IL-6 on outcome of patients with HBV-ACLF.

METHODS

We performed a retrospective study of 412 HBV-ACLF patients. The findings were analyzed with regard to mortality and the serum IL-6 level at baseline, as well as dynamic changes of serum IL-6 within 4 wk.

RESULTS

The serum IL-6 level was associated with mortality. Within 4 wk, deceased patients had significantly higher levels of IL-6 at baseline than surviving patients [17.9 (7.3-57.6) vs 10.4 (4.7-22.3), P = 0.011]. 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). The odds ratios calculated using univariate and multivariate logistic regression were 2.10 (95% confidence interval [CI]: 1.26-3.51, P = 0.005) and 2.11 (95%CI: 1.15-3.90, P = 0.017), respectively. 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).

CONCLUSION

A high level of serum IL-6 is an independent risk factor for mortality in patients with HBV-ACLF. Furthermore, a sustained high level or dynamic elevated level of serum IL-6 indicates a higher mortality.

Keywords: Hepatitis B virus, Liver failure, Prognosis, Interleukin-6

Core tip: To triage and prognosticate the outcome is vital for management of patients with hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF). Interleukin-6 (IL-6) is related with the physiology and pathology of the liver. We found that a high level of serum IL-6 was an independent risk factor for mortality in patients with HBV-ACLF. HBV-ACLF patients with high levels of IL-6 showed a high mortality, especially in those with persistent high levels within 4 wk, indicating that IL-6 is an index of prognosis for HBV-ACLF.