| Objective:To Analyze and compare the survival conditions of different native livers in BA patients after Kasai operation,and to explore the pathological characteristics of the liver in children with a longer survival time combining with the hepatic pathology and biochemistry.Meanwhile,to investigate the relationship of matrix metalloproteinase-7(MMP-7)in liver tissue of biliary atresia with liver fibrosis,bile duct reaction and biochemistry markers.Exploring the role of MMP-7 in the process of liver fibrosis and its clinical significance,and the effect on the survival native liver.Methods:1?43 BA patients who underwent Kasai and liver transplantation(LT)were divided into 3 groups according to the interval time between Kasai and LT:Group1(n=17),the interval time was less than 6 months;Group 2(n=18),the interval time ranged from 6 months to 2 years;Group 3(n=8),the interval time was more than 2 years.A retrospective study was conducted for clinical data of each group including the age at Kasai,the occurrence of cholangitis,and the biochemical value before LT.Meanwhile,pathological examinations of the liver pathology in Kasai and LT included hematoxylin-eosin(HE),Masson and immunohistochemical(CK19)staining for evaluating grade of liver fibrosis,extension of bile duct,cholestasis and infiltration of inflammatory cells.2?15 BA patients with liver biopsy when Kasai operation(Kasai group,G1)were collected,and 41 patients with liver biopsy who underwent liver transplantation after Kasai operation were enrolled(transplantation group).The transplantation group was divided into two groups according to the interval time between Kasai operation and liver transplantation:G2(n=28,the interval time was less than 2 years),G3(n=13,the interval time was more than 2 years).Hematoxylin-Eosin(HE)staining was used to observe the degree of liver fibrosis.Immunohistochemical staining was used to detect the expression of MMP-7 and CK19.The relationship between MMP-7 expression level and liver biochemistry index was also evaluated.Results1??The average age at Kasai were 66.65d,58.39d,49.63d(P=0.032)in three groups;The number of cases with cholangitis was 70.6%,77.8%,50%(P>0.05),and with frequent cholangitis after Kasai was 41.2%,66.7%,12.5%,and the difference was not statistically significantly;The biochemical value before LT showed that the level of AST,ALT,TBI,DBI and GGT in Group 3 was lower than the others,and the difference was not statistically significantly.?The grade of hepatic fibrosis was 3(2-3),bile duct proliferation was 2(1-2.5),portal bile plugs was 1(1-2.5),and infiltration of inflammatory cells was 3(1.5-3)at Kasai;The pathology at LT showed that the grade of hepatic fibrosis were4(4-4),4(4-4),4(2-4)(P=0.047),bile duct proliferation were 3(3-3),2(0.75-3),0(0-2)(P<0.001),bile plugs were 3(2.5-3),1(1-3)?1(1-3)(P<0.001),and infiltration of inflammatory cells were 2(1-2),1.5(1-2),1(1-1)(P=0.44)in three groups.The differences were statistically significantly.?The clinical and pathological data showed that:earlier the BA patients operated,less the frequency of cholangitisoccurred,slower the progress of hepatic fibrosis was,milder the bile duct proliferation cholestasis and inflammatory cell infiltration were,and longer the survival time of native liver was.2??Immunohistochemical results showed that MMP-7 was mainly expressed in bile duct epithelial cells,hyperplastic bile ducts,and hepatocytes around the portal area.As the degree of liver fibrosis progressed,the expression of MMP-7 in biliary duct cells and hepatocytes were increased,and biliary duct cells are more strongly expressed than hepatocytes.?Semi-quantitative analysis showed that there were significant differences in the expression of MMP-7 protein and CK19 among the three groups.The expression of MMP-7 and the level of CK19 protein in G2 were significantly higher than other two groups.There was no significant difference between G1 and G3.?The degree of liver fibrosis in the G2 was significantly higher than other two groups.Correlation test showed that the expression of MMP-7 protein was positively correlated with the degree of liver fibrosis(rs=0.609,P<0.001),but there was no correlation with bile duct reaction.Furthermore,the preoperative liver biochemistry examination showed that the expression level of MMP-7 protein was significantly correlated with total bile acid(TBA)(r=0.380,P=0.027).Conclusions:The age of Kasai and the frequency of cholangitis were essentials to the changes of native liver pathology and the survival time of BA patients.For BA patients with a longer native liver survival time,the Kasai operation resolved cholestasis and decreased inflammation infiltration which helps to delay the progress of liver fibrosis.At the same time,The expression of MMP-7 protein increased with the severity of liver fibrosis,and it was highly expressed in liver tissue after Kasai operetion which indicated that it may participate in and promote the process of BA liver fibrosis and suggested that native liver survive was poor. |
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