Increased Interleukin-23 Receptor (IL-23R) Expression is Associated with Disease Severity in Acute-on-Chronic Liver Failure.

BACKGROUND: Th17 cells mediated immune response is important in chronic hepatitis B (CHB) infection and inflammation associated diseases, however, little is known about their immunopathogenic role in acute-on-chronic liver failure (ACLF). Interleukin-23 receptor (IL-23R) is essential for the generation of pathogenic Th17 cells, therefore, we aimed to evaluate IL-23R expression and its correlation with disease severity in ACLF.

METHODS: Forty two patients with ACLF (HBV and alcohol-related), thirty two with CHB and twenty healthy controls (HC) were studied. Circulating and intrahepatic profile of Th17 cells and IL-23R was investigated. Association of IL-23R with disease severity was determined.

RESULTS: Circulating Th17 cells were significantly increased in both ACLF groups (p=0.03,p=0.006) than CHB and HC. Percentage of Th17 cells was higher in liver than peripheral blood of ACLF patients (p=0.04). Expression of IL-23R was immensely up-regulated on Th17 cells of ACLF patients. Importantly, IL-23R not only correlated with the increased percentage of Th17 cells but also had significant association with inflammation (p=0.03) and clinical disease severity indices including Child-Turcotte-Pugh (p=0.001) and Model for End-Stage Liver Disease (p=0.002) scores. The ACLF non-survivors showed higher IL-23R expression (p=0.01). Transcription factor retinoic acid receptor-related orphan nuclear receptor gamma-t (ROR-γt) was also high in circulation and in liver of ACLF patients and it positively correlated with ALT levels (p=0.03). Surface receptors, including CCR6, IL-17R and pro-inflammatory cytokines IL-17A, IL-22, CXCL8 and GM-CSF were highly augmented in ACLF.

CONCLUSION: ACLF patients express high IL-23R on Th17 cells which induces inflammation and strongly correlates with liver disease severity. This article is protected by copyright. All rights reserved.