The Role Of Serum β-Catenin In Differentiating Patients With HBV-Related Liver Diseases

Objection:Substantial evidence indicates that β-catenin is a pivotal regulator that contributes to the initiation and development of various types of diseases.Little recent studies have shown that β-catenin can be detected in human serum and correlated with the progression of some diseases.However,the relationship between serum β-catenin and HBV-related liver diseases is not clear.The purpose of this study was to investigate the relationship between serum β-catenin levels and HBV-related diseases and its possible application value.Methods:Serum levels of β-catenin,from 77 patients with chronic hepatitis B(CHB),63 patients with hepatitis B associated liver cirrhosis(HBLC),61 patients with hepatocellular carcinoma(HCC),41 healthy HBV carriers(HHCs)and 78 healthy controls(HCs)were measured by ELISA.Correlations of serum β-catenin with viral replication and liver necroinflammation parameters were analyzed by software Graphpad 6.0.The receiver operating characteristic(ROC)curve was used to assess the discriminating power of serum β-catenin to grade different stages of HBV-related disorders.Human hepatic cell line L02 was transfected with HBV DNA recombinant plasmids,and β-catenin levels in intracellular and supernatant were detected.At the same time,the changes of Akt and GSK-3β phosphorylation levels were detected,so as to preliminarily elucidate the mechanism of HBV affecting β-catenin.Results:Chronic hepatitis B and HBLC patients but not HHC or HCC showed significantly higher serum β-catenin levels than HCs.β-catenin levels were not correlated with HBV DNA levels but were correlated with necroinflammation parameters.HBV-infected cell model showed elevated levels of phosphorylation at Ser473 in Akt(p-Akt),phosphorylation at Ser9 in GSK3β(p-GSK3β)and β-catenin,all of which was blocked by treatment with Akt inhibitor LY294002.Additionally,ROC analysis of β-catenin for discriminating patients with CHB from HHCs,which yielded an AUC of 0.71(cutoff value,42 pg/mL;95% CI 0.61–0.81)with 64.93% sensitivity,73.17% specificity and 69.05% accuracy.ROC analysis of β-catenin for discriminating patients with HCC from chronic HBV infection mainly including CHB and HBLC,which yielded an AUC of 0.75(cutoff value,42 pg/mL;95% CI 0.67–0.83)with 66.43% sensitivity,75.41% specificity and 70.92% accuracy.Conclusion : HBV infection enhances β-catenin expression by activating Akt/GSK-3β signaling pathway in the cell model.Serum β-catenin levels are correlated with necroinflammation parameters but not with viral load.Serum β-catenin has potential to discriminate the phase of HBV-related disorders,particularly predicts the patients with CHB from HHCs and also predicting HCC from chronic HBV infection.