CTHRC1 serves as an indicator in biliary atresia for evaluating the stage of liver fibrosis and predicting prognosis.

ABSTRACT

BACKGROUND: Liver fibrosis is a pathological feature of biliary atresia (BA). However, both histological fibrosis stage and existing biomarkers fail to predict prognosis at the time of hepatoportonterostomy (HPE). AIMS: To explore the role of collagen triple- helix repeat containing-1 (CTHRC1) in BA. METHODS: CTHRC1 expression levels were detected and its association with liver fibrosis stage was analyzed in patients with BA. Immunohistochemistry and immunofluorescent analyses were performed to detect the expression and localization of CTHRC1. Epithelial-mesenchymal transition (EMT) and proliferation were analyzed in cholangiocytes treated with recombinant human CTHRC1 protein. Survival analyses were performed to assess the prognostic value of CTHRC1 in patients with BA. RESULTS: CTHRC1 was upregulated in BA, and its expression level was positively correlated with fibrosis-related markers and the severity of liver fibrosis. In liver tissue CTHRC1 was co-localized with CK19 and highly expressed in patients with severe liver fibrosis. Further experiments revealed that CTHRC1 promoted cholangiocyte EMT and proliferation. Additionally, CTHRC1 expression levels at HPE could predict the 2-year native liver survival (NLS). CONCLUSIONS: CTHRC1 promotes the EMT and proliferation of cholangiocytes and indicate the stage of liver fibrosis. The CTHRC1 expression levels can predict outcomes of BA.