The Clinical And Pathological Study In The Hepatic Fibrosis Of Biliary Atresia

Objective: To study the pathological change of hepatic fibrosis and cirrhosis in biliary atrsia and analysis of biliary atresia clinicopathological features of liver fibrosis in order to grade hepatic fibrosis of biliary atresia at the same time to be associate with its prognosis. Meanwhile, to observe the function of TGF-β1 and P-Smad3 in TGF-β1 signal pathways in liver fibrosis of biliary atresia.Methods:1. Liver biopsy specimens were collected from autopsy(n=6), biliary atresia patients who undergoing Kasai procedure(n=30), liver transplantation of biliary atresia(n=18), The hematoxylin&eosin staining and CK19 immunohistochemistry were used to observe portal tract lesions、fibrosis septa degree wide、the number of false flocculus、the degree of inflammatory cell inflitration and so on in these samples, all the clinical data of these samples were being collected also. To made a grade of hepatic fibrosis of BA and then find out the correlation between the grade and liver function.2. Liver biopsy specimens were collected from congenital biliary dilatation(CBD group, n=20), biliary atresia patients who had Kasai procedure(Early hepatic fibrosis group, n=20), liver transplantation(transplantation group, n=20). The hematoxylin & eosin staining were used to observe the degree of liver fibrosis of every single sample, immunohistochemistry were used to observe the expression of TGF-β1、Smad2-4、P-Smad2-3 and PAI-1 in liver tissues of these samples. To discuss the function of theses albumen in hepatic fibrosis of biliary atresia combine with “liver fibrosis grading standards of BA”.Results:1. ⑴.The hepatic fibrosis process of biliary atresia can be divided into grade 0 to 6, autopsy sample belonging to 0 level, Kasai sample belonging to 1-3level except for 1 sample which has pseudolobule and belonging to 4 level,all of the liver transplantation belonging to 4-6level. Level 0 parts without fibrous tissue hyperplasia, Level 1 portal tracts broadening to three times the size, limiting plate is visible, inflammatory cells in mesenchyma and P-P are mild hyperplasia, 2 levels of fibrosis continues to increase, Level 3 portal tracts broadening > 4 times, P-P are severe hyperplasia, pseudolobule appeared in 4 level, portal hepatic is too large to calculate, a lot of scar formation at 6 level. The fibrosis area of portal hepatic and P-P are significant becaming large between 0-4 level(P < 0.05), bile duct proliferation are more serious;the pseudolobule became more and more, inflamatory cells and bile duct are less until dissmising or fibrillation between 4-6 level. ⑵. The 0-6 levels hepatic fibrosis of biliary atresia gradually aggravate and liver function declined at the same time.2. The CBD group had mild fiber cells hyperplasia, the Kasai group had Proliferation of collagen fibers and bridging fibrosis phenomenon,the transplantation group had significant pseudolobule. The level of TGF-β1、Smad3、P-Smad3 and PAI-1 in the Kasai group have a significant rise than the other groups(p<0.05), the hepatic fibrosis is becoming serious with the rise of TGF-β1、Smad3、P-Smad3 and PAI-1, at the same time The correlation between P-Smad3 and hepatic fibrosis of biliary atresia was remarkable; All of the proteins in the TGF-β1 signal pathways were decreased in transplantation group(p<0.05).Conclusions: The hepatic fibrosis pathological changes of biliary atresia is significantly. The hepatic fibrosis grade of biliary atresia could reflect the physical truth of fibrosis during operation and it indicates for liver cirrhosis with poor prognosis if hepatic fibrosis grade above 3 level. At the same time,TGF-β1 and Smad3 made a contribution to liver fibrosis in the 1-6 levels of biliary atresia,and P-Smad3 is closely related with the progress of liver fibrosis.