Increased Th17 cells contribute to disease progression in patients with HBV‐associated liver cirrhosis

Abstract

T helper (Th) 17 cells have been demonstrated to participate in the pathogenesis of HBV-associated liver damage. However, little is known regarding the immunopathogenic role of liver fibrosis in patients with HBV-associated liver cirrhosis. The aims of this study were to evaluate whether Th17 cells are related to disease progression in patients and to explore the possible mechanisms. The frequencies of circulating Th17 cells were analysed in 78 patients with hepatitis B and cirrhosis (Child A: 34; Child B: 22; Child C 22) and matched controls. Liver samples were collected from 13 patients with HBV-associated cirrhosis, 23 patients with chronic hepatitis B and 12 healthy controls for immunohistochemical analysis. IL-17 receptor expression was studied on liver biopsies and in human hepatic stellate cells as well as their response to recombinant IL-17 by flow cytometry. Patients with hepatitis B-associated cirrhosis with more severe disease displayed significant increases in peripheral numbers of Th17 cells as well as in IL-17 plasma levels. The increased intrahepatic IL-17(+) cells correlated positively with fibrotic staging scores and clinical progression from CHB to cirrhosis. Moreover, many IL-17(+) cells were located in fibrotic areas in the liver of patients with cirrhosis. In vitro, IL-17 together with IL-17-activated monocytes, could promote the activation of stellate cells, which, in turn, aggravated liver fibrosis and the inflammatory response. In summary, increased peripheral and intrahepatic Th17 cells are enriched in patients with hepatitis B and cirrhosis and contribute further to the severity of disease progression through induction of stellate cell activation.