The Ratio of Th-17 to Treg Cells is Associated with Survival of Patients with Acute-on-Chronic Hepatitis B Liver Failure

Both T-helper 17 cells (Th-17) and CD4(+)CD25(+) regulatory T cells (Tregs) play important roles in the pathogenesis of hepatitis B virus (HBV) infection. Recent studies have suggested that Th-17 and Treg cells are increased in patients with chronic hepatitis B (CHB). This study further characterizes Th-17 and Treg cells in the blood of HBV-associated acute-on-chronic liver failure (ACLF) patients, and aids our understanding of how the two subsets of CD4(+) T cells affect each other and contribute to survival. Blood samples were obtained from 30 patients with HBV-associated ACLF, 30 patients with CHB, and 30 normal controls (NC). The frequencies of Th-17 and Treg cells were determined by intracellular cytokine staining analysis. To observe the suppressive function of Tregs, purified CD4(+)CD25(+) Tregs from peripheral blood mononuclear cells (PBMCs) were co-cultured with CD4(+)CD25(-) T cells for 48 h, and then IFN-gamma and IL-17A from the supernatants were measured by ELISA. We found that both Th-17 and FoxP3(+) Treg cells were increased in ACLF patients. IL-17A secretion by CD4(+) T cells was not regulated by Treg cells, even though Tregs exhibited significant inhibition of IFN-g production. Most importantly, the ratio of Th-17 to Treg cells was associated inversely with the survival of ACLF patients. These findings provide new information regarding the pathogenesis of HBV-associated ACLF, and the ratio of Th-17 to Tregs may represent a potential prognostic marker for the disease.