Treg/Th17 Cell Balance in Patients with Hepatitis B Virus‐Related Acute‐on‐Chronic Liver Failure at Different Disease Stages
Nian-Hua Tan, Bin Chen, PENG Jie, Shan Du
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.