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

Abstract

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.

Correlation between T-Lymphocyte Subsets, Regulatory T Cells, and Hepatic Fibrosis in Patients with Nonalcoholic Fatty Liver

“…Treg and Th17 cells are CD4+ T cells different from classical Th1 and Th2 cells. Treg cells mainly secrete IL-10 and TGF- β 1, which improve hepatocyte inflammation by regulating other immune cell functions and thus controlling the body's immune response, while Th17 cells mainly secrete inflammatory factors such as IL-17 and IL-22 and induce proinflammatory factors such as IL-6 and TNF- α , both of which antagonize each other in function and differentiation [ 20 ]. We can also fully confirm this after testing the inflammatory factors and OS responses in NAFLD patients and healthy persons.…”

Predictive Values of Programmed Death-1, CC Chemokine Ligand 20, and Treg/T Helper 17 Cytokines for Patients with Hepatitis B Virus-Related Acute-on-Chronic Liver Failure

“…CC chemokine ligand 20, a chemotactic protein secreted by hepatocytes, is expressed in liver tissues, facilitating the development of inflammatory responses in liver tissues (22,23). Moreover, Treg/Th17 cytokines are important players in immuno-inflammatory regulation (24). The changes in the levels of Treg/Th17 cytokines (TGF-β, IL-10, IL-23, and TNF-α) are closely related to the Treg/Th17 balance.…”

CHINAT-CD4 Score Predicts Transplant-Free Survival in Patients with Acute-on-Chronic Liver Failure

“… 20 Additionally, previous studies demonstrated CD4+CD25+ T-regulatory cells were independent risk factors for patients with ACLF. 21 , 22 …”