| Objective: To investigate the relationship between matrix metalloproteinase-13 expression in biliary atresia liver and liver fibrosis staging,liver function,serological models of liver fibrosis and the rate of decline in postoperative jaundice to provide a basis for predicting liver fibrosis and prognosis in biliary atresia.Methods: The liver tissues of 56 children with biliary atresia and 12 children with congenital biliary dilatation who were archived and treated at the Affiliated Hospital of Zunyi Medical University were firstly selected as the observation group and the control group in this study,and after HE staining,liver fibrosis staging was performed according to Metavir criteria,and the expression of matrix metalloproteinase-13 in liver tissues was detected by immunohistochemistry and analyzed semi-quantitatively to observe the expression of matrix metalloproteinase-13 in the control group,each The expression of matrix metalloproteinase-13 protein in liver tissues at each stage of fibrosis was observed.Liver function and blood tests were collected and serological models of APRI,GPR and S index were calculated to analyse their correlation with matrix metalloproteinase-13 protein.According to the fibrosis progression,the groups were divided into no progressive liver fibrosis(F<3)and progressive liver fibrosis(F≥3),no cirrhosis(F<4)and cirrhosis(F=4).The clinical value of matrix metalloproteinase-13 for predicting the probability of liver fibrosis staging was determined based on the area under the working characteristic curve of the subjects and the optimal threshold value was found by the Jorden index.The age of patients at surgery was collected and children with biliary atresia were divided into three groups of <60 days,60～90 days and >90 days to analyse the expression of MMP-13 in the liver of children with BA at different surgery days;the patients were followed up at 3 and 6 months after surgery for the correlation between the expression of MMP-13,surgery days and fibrosis staging and the rate of jaundice reduction after Kasai surgery.Results: According to the Metavir standard,the 56 children with biliary atresia were divided into F0(0 cases),F1(0 cases),F2(7 cases),F3(11 cases),and F4(38 cases).The expression of MMP-13 protein in F2,F3,and F4 was higher than that of the control group,and the difference was statistically significant(P<0.001).The average optical density of MMP-13 in F2,F3,and F4 gradually increased with the progress of liver fibrosis,and the difference between the two groups was statistically significant.The area under the curve of MMP-13 for predicting progressive liver fibrosis(F≥3)was 0.942(95%CI: 0.872-1.000),the best cut-off value was 99.28,sensitivity: 79.59%,specificity: 100%,Negative predictive value:41.17%,positive predictive value: 100%.The area under the curve of MMP-13 for predicting liver cirrhosis(F=4)was 0.721(95%CI: 0.585-0.857),the best cut-off value was 107.9,sensitivity: 71.05%,specificity: 66.67%,negative predictive value: 52.17%;positive predictive value: 81.82%.The average optical density of MMP-13 was positively correlated with TBIL,DBIL,and TBA,and the correlation was statistically significant(P<0.001);it was positively correlated with ALP,GGT,and IBIL,and the correlation was statistically significant(P <0.05);the average optical density value of MMP-13 was negatively correlated with PA,the r value was-0.284,P=0.019,which was statistically significant;it was significantly correlated with ALT,AST,AAR,CHE,TP,ALB,GLB,A/G correlation was not statistically significant(P>0.05).In the serological model,it was found that the average optical density of MMP-13 had no significant correlation with APRI(r=0.115,P=0.352),but was positively correlated with GPR and S index,with statistical significance(P<0.05).The levels of MMP-13 in the liver tissue of the three groups of <60 days,60～90 days,and >90 days were all higher than those of the control group,and the difference was statistically significant(P<0.001).MMP-13 in the liver tissue of children with BA gradually increased with the increase of the age of operation,and the differences were found to be statistically significant after pairwise comparison between the groups(P<0.001).The Spearman correlation analysis between liver fibrosis stage and age at surgery showed that there was a positive correlation between stage of liver fibrosis and age at surgery,and the correlation coefficient was 0.380,which was statistically significant(P=0.001).MMP-13 was negatively correlated with TBIL decline rate 3 months after operation(r=-0.830,P<0.001),and the decrease rate of total bilirubin at 3 months after operation was the lowest at 9.1% and the highest at 94.7%;MMP-13 It was negatively correlated with the decrease rate of TBIL at 6 months after operation(r=-0.693,P=0.004).The decrease rate of total bilirubin at 6 months after operation was the lowest of 14.3% and the highest of 95.6%.It was observed that the age of operation was negatively correlated with the rate of jaundice decline 3 months after operation,and the correlation coefficient was-0.629,which was statistically significant(P<0.001);it was negatively correlated with the rate of jaundice decline 6 months after operation,and the correlation coefficient was-0.677,which was statistically significant(P=0.006).Spearman correlation analysis between the degree of liver fibrosis at the time of surgery and the rate of postoperative jaundice reduction showed that the fibrosis stage at the time of surgery was negatively correlated with the rate of jaundice reduction 3 months after surgery,with a correlation coefficient of-0.445,which was statistically significant(P=0.016);it was negatively correlated with the decrease rate of jaundice 6 months after operation,and the correlation coefficient was-0.576,which was statistically significant(P=0.025).Conclusions: The expression of MMP-13 is significantly increased in the liver of children with biliary atresia,and MMP-13 can be used as a predictor of postoperative liver fibrosis in children with biliary atresia.The expression of MMP-13 in the liver of children with biliary atresia is positively correlated with GPR,a serological model of liver fibrosis.MMP-13 is one of the diagnostic criteria for the degree of hepatic fibrosis in children with biliary atresia.The older the age of Kasai operation,the higher the expression of MMP-13 in the liver of children with biliary atresia;the higher the expression of MMP-13 in the liver of children with biliary atresia,the lower the rate of jaundice at 3 and 6 months after surgery lower. |
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