Treg/Th17 Cell Balance in Patients with Hepatitis B Virus-Related Acute-on-Chronic Liver Failure at Different Disease Stages

• Published in: BioMed research international Vol. 2021; pp. 9140602 - 13
• Main Authors: Tan, Nian-Hua, Chen, Bin, Peng, Jie, Du, Shan
• Format: Journal Article
• Language: English
• Published: United States Hindawi 2021; Hindawi Limited
• Subjects: Acute-On-Chronic Liver Failure - immunology; Acute-On-Chronic Liver Failure - pathology; Acute-On-Chronic Liver Failure - virology; Adult; Biomarkers; Biomedical research; Blood; C-reactive protein; CD25 antigen; CD4 antigen; China; Correlation; Creatinine; Cytokines; Effector cells; Failure; Female; Flow cytometry; Foxp3 protein; Gene expression; Growth factors; Helper cells; Hepatitis; Hepatitis B; Hepatitis B virus - immunology; Hepatitis B, Chronic - immunology; Hepatitis B, Chronic - pathology; Hepatitis B, Chronic - virology; Herbal medicine; Hospitals; Humans; Infections; Inflammation; Inflammatory response; Interleukin 10; Interleukin 23; Interleukins - immunology; Laboratories; Lipopolysaccharides; Liver; Liver diseases; Liver failure; Lymphocytes T; Male; Middle Aged; Nuclear Receptor Subfamily 1, Group F, Member 3 - immunology; Pathogenesis; Patients; Peripheral blood; Procalcitonin; Risk analysis; Risk factors; Software; T-Lymphocytes, Regulatory - immunology; Th17 Cells - immunology; Transcription factors; Transforming growth factor-b; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Viruses; China; United States > US
• ISSN: 2314-6133; 2314-6141
• DOI: 10.1155/2021/9140602

Background. T-helper 17 (Th17) and CD4+CD25+ T-regulatory (Treg) cells play important roles in the pathogenesis of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). This study is aimed at investigating shifts in Treg/Th17 balance in the peripheral blood of HBV-ACLF patients at different disease stages. Methods. Sixty HBV-ACLF patients, admitted to the First Hospital of Hunan University of Chinese Medicine, China, including early-stage (n=20), middle-stage (n=20), and late-stage patients (n=20), were enrolled in the study. In addition, 20 patients with chronic hepatitis B and 20 healthy volunteers were also included in the study as controls. Flow cytometry, cytometric bead array, and quantitative real-time PCR protocols were used to evaluate the expression of Treg and Th17 cells as well as of related cytokines. Results. The levels of Th17 cells and their effectors interleukin- (IL-) 17A, IL-23, and tumor necrosis factor-α increased with disease progression. Similarly, Treg cells and their effector cytokines transforming growth factor-β and IL-10 also increased. Although Treg and Th17 levels were positively correlated, the latter were always at higher numbers. Noteworthy, the Treg/Th17 ratio gradually decreased and was negatively correlated with ACLF severity. FoxP3 levels in the peripheral blood gradually decreased with ACLF progression, whereas ROR-γt gradually increased. Serum c-reactive protein, procalcitonin, and lipopolysaccharide were also upregulated with disease progression and positively correlated with Th17 abundance. Further, Th17, IL-17A, and IL-23 were independent risk factors for ACLF. A prognostic model for HBV-ACLF was established, with a correct prediction rate of 90.00% (54/60). Conclusion. Treg/Th17 imbalance occurs throughout the pathogenic course of HBV-ACLF, with an imbalance shift toward Th17. Hence, the Th17-mediated inflammatory response drives HBV-ACLF-associated inflammation and supports the pathological mechanisms of liver failure.