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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.

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