Associations of Wnt5a expression with liver injury in chronic hepatitis B virus infection

Abstract

Background: Aberrant Wnt5a expression contributes to immunity, inflammation and tissue damage. However, it remains unknown whether Wnt5a is associated with liver injury in chronic hepatitis B virus (HBV) infection. We aimed to explore the potential role of Wnt5a expression in liver injury caused by chronic HBV infection.

Methods: Wnt5a mRNA levels in peripheral blood mononuclear cells (PBMCs) were analyzed in 31 acute-on-chronic hepatitis B liver failure (ACHBLF) patients, 82 chronic hepatitis B (CHB) patients, and 20 healthy controls using quantitative real-time polymerase chain reaction. Intrahepatic Wnt5a protein expression from 32 chronic HBV infection patients and 6 normal controls was evaluated by immunohistochemical staining.

Results: Wnt5a mRNA expression was increased in CHB patients and ACHBLF patients compared to healthy controls and correlated positively with liver injury markers. Additionally, there was a significant correlation between Wnt5a mRNA expression and HBV DNA load in all patients and CHB patients but not in ACHBLF patients. Furthermore, intrahepatic Wnt5a protein expression was elevated in chronic HBV infection patients compared to that in normal controls. Moreover, chronic HBV infection patients with higher hepatic inflammatory grades had increased intrahepatic Wnt5a protein expression compared with lower hepatic inflammatory grades. In addition, the cut-off value of 12.59 for Wnt5a mRNA level was a strong indicator in predicting ACHBLF in CHB patients.

Conclusions: We found that Wnt5a expression was associated with liver injury in chronic HBV infection patients. Wnt5a might be involved in exacerbation of chronic HBV infection.

Keywords: Chronic Hepatitis B; Chronic Hepatitis B virus Infection; Liver injury; Wnt5a.

Fig. 1

Inclusive procession of ACHBLF patients and CHB patients in this present study was shown in the flowchart

Fig. 2

Relative expression of Wnt5a mRNA and its associated cytokines were determined in PBMCs from ACHBLF patients, CHB patients and healthy controls. Relative expression of Wnt5a (A), TNF-α (B), IL-6 (C) and IL-1β (D) mRNA in PBMCs from ACHBLF patients, CHB patients and healthy controls. * P < 0.05

Fig. 3

Correlations between Wnt5a mRNA expression and liver injury markers, HBV DNA load and inflammatory cytokines were analyzed in CHB and ACHBLF patients. Correlations between Wnt5a mRNA expression and serum ALT (A), AST (B), TBIL (C), HBV DNA load (D), TNF-α (E) and IL-6 (F). * P < 0.05

Fig. 4

Predicative value for Wnt5a mRNA was evaluated in discriminating ACHBLF from CHB. The AUROC was 0.847 (95% CI: 0.734–0.925)

Fig. 5

Intrahepatic Wnt5a protein expression was determined in patients with chronic HBV infection and normal controls by immunohistochemical staining. Representative immunohistochemical photographs for intrahepatic Wnt5a protein in normal controls (A) and chronic HBV infection patients with hepatic inflammatory grade scores G1 (B) and G3 (C) (magnification, × 400). D. Quantitative analysis of Wnt5a immunohistochemistry staining. * P < 0.05. AOD, average optical density