Zhang Y, Tian XL, Li JQ, Wu DS, Li Q, Chen B. Mitochondrial dysfunction affects hepatic immune and metabolic remodeling in patients with hepatitis B virus-related acute-on-chronic liver failure. World J Gastroenterol 2024; 30(8): 881-900 [PMID: 38516248 DOI: 10.3748/wjg.v30.i8.881]
Corresponding Author of This Article
Bin Chen, PhD, Chief Physician, Department of Hepatology, Institute of Hepatology, The First Affiliated Hospital of Hunan University of Chinese Medicine, No. 95 Middle Shaoshan Road, Yuhua District, Changsha 410021, Hunan Province, China. chenbin0410@126.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Observational Study
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Zhang Y, Tian XL, Li JQ, Wu DS, Li Q, Chen B. Mitochondrial dysfunction affects hepatic immune and metabolic remodeling in patients with hepatitis B virus-related acute-on-chronic liver failure. World J Gastroenterol 2024; 30(8): 881-900 [PMID: 38516248 DOI: 10.3748/wjg.v30.i8.881]
Yu Zhang, Xiao-Ling Tian, Bin Chen, Department of Hepatology, Institute of Hepatology, The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha 410021, Hunan Province, China
Jie-Qun Li, Qiang Li, Department of Liver Transplant, Transplant Medical Research Center, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China
Dong-Sheng Wu, Department of Surgery, The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha 410021, Hunan Province, China
Author contributions: Zhang Y and Tian XL performed experiments, analysed data and wrote the paper; Wu DS and Li Q performed experiments and analysed data; Li JQ and Chen B designed experiments, performed experiments and edited the paper.
Supported bythe Domestic First-class Construction Disciplines of the Hunan University of Chinese Medicine; Postgraduate Research Innovation Program of Hunan Province, No. CX20220771; and Clinical MedTech Innovation Project of Hunan Province, No. 2021SK51415.
Institutional review board statement: The study protocol was approved by the Ethics Committee of the First Hospital of Hunan University of Chinese Medicine (No. HN-LL-SWST-15), and written informed consent was obtained from all participants.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors declare no conflicts of interest that pertain to this work.
Data sharing statement: All data generated or analyzed during this study are included in this published article.
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.
Corresponding author: Bin Chen, PhD, Chief Physician, Department of Hepatology, Institute of Hepatology, The First Affiliated Hospital of Hunan University of Chinese Medicine, No. 95 Middle Shaoshan Road, Yuhua District, Changsha 410021, Hunan Province, China. chenbin0410@126.com
Received: October 8, 2023 Peer-review started: October 8, 2023 First decision: December 8, 2023 Revised: December 15, 2023 Accepted: January 23, 2024 Article in press: January 23, 2024 Published online: February 28, 2024 Processing time: 141 Days and 10.7 Hours
ARTICLE HIGHLIGHTS
Research background
Immune dysregulation and metabolic derangement have been recognized as key factors that contribute to the progression of hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF).
Research motivation
Currently, the mechanisms underlying immune and metabolic derangement in patients with advanced HBV-ACLF are unclear.
Research objectives
To identify the bioenergetic alterations in the liver of patients with HBV-ACLF causing hepatic immune dysregulation and metabolic disorders.
Research methods
This study evaluated the mitochondrial ultrastructure, metabolic characteristics, and immune microenvironment of the liver of the subjects.
Research results
There was extensive hepatocyte necrosis, immune cell infiltration, and ductular reaction in the liver of patients with ACLF. Hypoxia significantly changed the ultrastructure of mitochondria as evidenced by mitochondrial swelling and ridge destruction. Mitochondrial oxidative phosphorylation decreased, while anaerobic glycolysis was enhanced in patients with HBV-ACLF. Circulating monocyte-derived macrophages widely infiltrated the liver of patients with HBV-ACLF. Patients with ACLF had a high abundance of CD68+ HLA-DR+ macrophages and elevated levels of both interleukin-1β and transforming growth factor-β1 in their livers. The abundance of CD206+ CD163+ macrophages and expression of interleukin-10 decreased.
Research conclusions
Bioenergetic alteration driven by hypoxia and mitochondrial dysfunction affects hepatic immune and metabolic remodeling, leading to advanced HBV-ACLF.
Research perspectives
Regulating liver metabolism reprogramming and promoting the polarization of alternatively activated macrophages may attenuate liver inflammation and promote tissue repair. This provides insights to treatment strategies that are worth exploring.
