Th17/Treg imbalance and increased interleukin-21 are associated with liver injury in patients with chronic severe hepatitis B

•The ratio of Th1/Treg is imbalanced in chronic severe hepatitis B.•Serum levels of Th17 related cytokines are higher in chronic severe hepatitis B.•Increased IL-21 and IFN-γ are associated with liver injury in chronic hepatitis B.•Frequency of circulating Th17 cells is increased and Th1 is decreased in chronic hepatitis B.•Frequency of circulating Treg cells is increased in asymptomatic hepatitis B virus carriers.

BackgroundTh17/Treg imbalance and the levels of related cytokines are essential in the pathogenesis of autoimmune and infectious diseases. The aim of the current study was to assess the Treg/Th17 balance and the levels of related cytokines associated with various degrees of liver injury in patients with chronic hepatitis B virus (HBV) infection.MethodsThe proportions of peripheral Th17, Treg and Th1 cells in 7 patients classified as asymptomatic hepatitis B virus carriers (AsCs), 38 patients with low or moderate grade chronic hepatitis B (CHB-LM), 20 patients with chronic severe hepatitis B (CSHB), and 10 healthy controls (HCs) were determined by flow cytometry. The levels of related cytokines and the mRNA expression levels of transcription factors were measured using Enzyme-linked immunosorbent assay (ELISA) and real-time quantitative PCR (RT-PCR), respectively.ResultsThe Th17 cell frequency and the mRNA expression levels of RORc were increased in the CSHB group. The Treg cell frequency was increased and Th1 cell frequency and the mRNA expression levels of T-bet were decreased in chronic HBV infection. The levels of IL-21 were increased in the CSHB group and were positively correlated with AST, TB and DB in patients with chronic HBV infection. The Th17/Treg ratio was increased in the CSHB group and was positively correlated with liver injury in chronic HBV infection.ConclusionsTh17/Treg imbalance and increased IL-21 are associated with liver injury in patients with chronic HBV infection. Restoring the Th17/Treg balance may be a novel immunotherapy for patients with CSHB.