Expression and clinical significance of MMP-13 in the liver of children with biliary atresia
Authors: Xiong Xian-Gang , Zheng Ze-Bing , Liu Yuan-Mei , Liao Yu , Qin Xu-Dong , Zhao Xiao-Huan , Gong Yuan , Tang Cheng-Yan , Jin Zhu 
Published: July 2024

Abstract

Objective: This study aims to investigate the correlation between matrix metalloproteinase-13 (MMP-13) expression in the liver of patients with biliary atresia and various factors including liver fibrosis stage, liver function indices, serological models of liver fibrosis, and the rate of jaundice resolution post-surgery. This investigation seeks to establish a basis for predicting liver fibrosis progression and the prognosis of biliary atresia.
Methods: Liver tissues from 56 children with biliary atresia and 12 with congenital biliary dilatation treated at the Affiliated Hospital of Zunyi Medical University were selected, forming the study's observation and control groups, respectively. Liver fibrosis was staged using the Metavir scoring system following hematoxylin and eosin (HE) staining. Immunohistochemistry was utilized to detect MMP-13 expression in liver tissue, followed by semi-quantitative analysis. Expression levels were compared across different stages of fibrosis and correlated with liver function tests and the serological models APRI, GPR, and S index. Patients were categorized into non-progressive and progressive liver fibrosis groups, as well as non-cirrhotic and cirrhotic groups, based on fibrosis stage. The predictive value of MMP-13 for liver fibrosis stages was assessed using the area under the receiver operating characteristic (ROC) curve and the Youden index was applied to determine the optimal cut-off value. Additionally, the relationship between the age at surgery and MMP-13 expression, as well as the correlation between MMP-13 expression and the rate of jaundice resolution after Kasai surgery, was analyzed.
Results: Among the 56 children with biliary atresia, liver fibrosis stages were distributed as follows: F0 (0 cases), F1 (0 cases), F2 (7 cases), F3 (11 cases), and F4 (38 cases). The control group of 12 children with congenital biliary dilatation all had F0 fibrosis. MMP-13 protein expression was significantly higher in the F2, F3, and F4 stages compared to the control group (P < 0.001), with expression intensifying as fibrosis progressed. The ROC curve analysis indicated a high predictive accuracy of MMP-13 for progressive liver fibrosis (AUC = 0.942) and cirrhosis (AUC = 0.721). MMP-13 expression showed positive correlations with biochemical markers of cholestasis and negative correlations with prothrombin activity. No significant correlations were found with other liver function tests. MMP-13 expression was also positively correlated with the GPR and S index but not with APRI. In children undergoing Kasai surgery, older age at surgery was associated with higher MMP-13 expression, and higher MMP-13 expression was linked to a lower rate of jaundice resolution post-surgery.
Conclusion: Elevated MMP-13 expression in the liver of children with biliary atresia correlates with the progression of liver fibrosis and serological fibrosis markers. It serves as a potential prognostic indicator for post-surgical liver fibrosis in these patients. Furthermore, age at the time of surgery influences MMP-13 expression levels and the efficacy of jaundice resolution following surgery.