Increased Th17 cells and interleukin-17 contribute to immune activation and disease aggravation in patients with chronic hepatitis B virus infection

Abstract

T helper17 (Th17) cells have been demonstrated to participate in the pathogenesis of hepatitis B virus (HBV) associated liver damage. However, the contribution of Th17 cells to immune activation and disease aggravation in patients with HBV infection is not fully clear. In this study, we investigated the Th17 cells frequencies and interleukin-17 (IL-17) mRNA expressions in peripheral blood mononuclear cells (PBMCs), intrahepatic IL-17-positive cells accumulation, as well as serum IL-17 levels in asymptomatic chronic HBV carriers (AsC), and patients with chronic hepatitis B (CHB) and HBV related acute-on-chronic liver failure (ACLF). Furthermore, the dynamic changes of Th17 cells frequencies and IL-17 concentration in different prognostic ACLF patients were observed. As result, the intrahepatic and peripheral Th17 cells and serum IL-17 concentration were both significantly higher in CHB and HBV related ACLF patients than that in AsC and normal control groups, and increased gradually with immune inflammation aggravation from AsC, CHB to ACLF. Moreover, in ACLF patients, peripheral Th17 cells frequencies were positively correlated with international normalized ratio (INR) and model of end-stage liver disease (MELD) score. Especially the survival patients had an initially lower Th17 cells frequencies and IL-17 levels which gradually decreased following condition improvement as compared with higher baseline level followed by gradually increasing trend in the non-survivals. In conclusion, Th17 cells can be contributed to the immune activation and disease aggravation in patients with chronic HBV infection. This may places Th17 cells as a potential blocking target for controlling CHB and ACLF.