Observational Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 21, 2020; 26(31): 4703-4717
Published online Aug 21, 2020. doi: 10.3748/wjg.v26.i31.4703
Mucosal-associated invariant T cells in hepatitis B virus-related liver failure
Hong Xue, Han Li, Lin-Ling Ju, Xu-Dong Han, Tiao-Chun Cheng, Xi Luo, Lin Chen, Jian-Guo Shao, Yong-Jun She, Zhao-Lian Bian
Hong Xue, Department of Liver Diseases, Nantong Third People’s Hospital, Nantong University, Nantong 226006, Jiangsu Province, China
Han Li, Tiao-Chun Cheng, Medical School of Nantong University, Nantong 226006, Jiangsu Province, China
Lin-Ling Ju, Xi Luo, Lin Chen, Jian-Guo Shao, Zhao-Lian Bian, Nantong Institute of Liver Diseases, Nantong Third People’s Hospital, Nantong University, Nantong 226006, Jiangsu Province, China
Xu-Dong Han, Department of Critical Care Medicine, Nantong Third People’s Hospital, Nantong University, Nantong 226006, Jiangsu Province, China
Jian-Guo Shao, Zhao-Lian Bian, Department of Gastroenterology and Hepatology, Nantong Third People’s Hospital, Nantong University, Nantong 226006, Jiangsu Province, China
Yong-Jun She, Department of Anesthesiology, Nantong Third People’s Hospital, Nantong University, Nantong 226006, Jiangsu Province, China
Author contributions: Xue H, Li H and Ju L-L contributed equally to this work; Xue H and Ju L-L performed the flow cytometry analysis; Li H and Cheng T-C wrote the manuscript; Luo X and Chen L performed the statistical analysis; Han X-D, Shao J-G and She Y-J revised the manuscript; Bian Z-L designed the study and revised the manuscript.
Supported by National Natural Science Foundation of China, No. 81600449; Nantong Science and Technology Bureau, No. MS22018007, No. MSZ18130, and No. JCZ18036; Six Peak Talents in Jiangsu Province, No. YY-177; Project of Jiangsu Province Youth Medical Talent Development, No. QNRC2016400; and Project of Nantong Youth Medical Talent Development, No. 05.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of Nantong Third People’s Hospital Affiliated to Nantong University, Nantong, China.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: There are no conflicts of interest to report.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
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: Zhao-Lian Bian, MD, PhD, Associate Professor, Department of Gastroenterology and Hepatology, Nantong Third People’s Hospital, Nantong University, No. 60 Middle Qingnian Road, Nantong 226006, Jiangsu Province, China. bianzhaolian1998@163.com
Received: March 2, 2020
Peer-review started: March 2, 2020
First decision: April 25, 2020
Revised: May 21, 2020
Accepted: July 30, 2020
Article in press: July 30, 2020
Published online: August 21, 2020
Processing time: 171 Days and 10 Hours
Abstract
BACKGROUND

Liver failure has high mortality and poor prognosis, and establishing new reliable markers for predicting its prognosis is necessary. Mucosal-associated invariant T (MAIT) cells are a novel population of innate-like lymphocytes involved in inflammatory liver disease, and their potential role in liver failure remains unclear.

AIM

To investigate alteration of circulating MAIT cells and assess its prognostic value in patients with hepatitis B virus (HBV)-related liver failure.

METHODS

We recruited 55 patients with HBV-related liver failure, 48 patients with chronic hepatitis B and 40 healthy controls (HCs) from Nantong Third People’s Hospital Affiliated to Nantong University. Peripheral blood mononuclear cells were isolated, and the percentage and number of circulating MAIT cells were detected by flow cytometry. Plasma levels of interleukin (IL)-7, IL-12p70, IL-18 and interferon-α were measured by Luminex assay.

RESULTS

Circulating MAIT cells were significantly decreased in HBV-related liver failure patients (percentage: 2.00 ± 1.22 vs 5.19 ± 1.27%, P < 0.0001; number: 5.47 ± 4.93 vs 84.43 ± 19.59, P < 0.0001) compared with HCs. More importantly, there was a significant reduction of MAIT cells in patients with middle/late-stage compared with early-stage liver failure. Circulating MAIT cells partially recovered after disease improvement, both in percentage (4.01 ± 1.21 vs 2.04 ± 0.95%, P < 0.0001) and in cell count (17.24 ± 8.56 vs 7.41 ± 4.99, P < 0.0001). The proportion (2.29 ± 1.01 vs 1.58 ± 1.38%, P < 0.05) and number (7.30 ± 5.70 vs 2.94 ± 1.47, P < 0.001) of circulating MAIT cells were significantly higher in the survival group than in the dead/liver transplantation group, and the Kaplan–Meier curve showed that lower expression of circulating MAIT cells (both percentage and cell count) predicted poor overall survival (P < 0.01). Also, the levels of IL-12 (20.26 ± 5.42 pg/mL vs 17.76 ± 2.79 pg/mL, P = 0.01) and IL-18 (1470.05 ± 1525.38 pg/mL vs 362.99 ± 109.64 pg/mL, P < 0.0001) were dramatically increased in HBV-related liver failure patients compared with HCs.

CONCLUSION

Circulating MAIT cells may play an important role in the process of HBV-related liver failure and can be an important prognostic marker.

Keywords: Mucosal-associated invariant T cells; Chronic hepatitis B; Liver failure; Prognosis; Hepatitis B virus

Core tip: Our data showed that lower expression of circulating mucosal-associated invariant T cells indicates poor prognosis of hepatitis B virus-related liver failure. We conclude that mucosal-associated invariant T cells are a new reliable marker for predicting the prognosis for hepatitis B virus-related liver failure patients and helpful for clinical decision-making.