Published online Feb 28, 2016. doi: 10.3748/wjg.v22.i8.2545
Peer-review started: July 30, 2015
First decision: October 15, 2015
Revised: November 4, 2015
Accepted: December 19, 2015
Article in press: December 19, 2015
Published online: February 28, 2016
Processing time: 211 Days and 1.8 Hours
AIM: To analyze the clinical and pathological parameters and expression of the neural cell adhesion molecule (CD56) in patients with biliary atresia (BA).
METHODS: Established clinical laboratory markers of hepatic function, including enzyme activity, protein synthesis, and bilirubin metabolism, were evaluated in patients with BA and compared with those in patients with choledochal cysts and neonatal hepatitis. Pathological changes in tissue morphology and fibrosis were examined by histological and tissue collagen staining. Immunohistochemical staining for the biliary epithelial cell markers CD56 and CK19 together with the Notch signaling related molecules Notch1 and Notch2 was performed in the context of alterations in the structure of intrahepatic biliary ducts.
RESULTS: Differences in some clinical laboratory parameters among the three diseases examined were observed, but they did not correlate with the pathological classification of fibrosis in BA. Immunohistochemical staining showed the presence of CD56-positive immature bile ducts in most patients (74.5%) with BA but not in patients with choledochal cysts or neonatal hepatitis. The number of CD56-expressing cells correlated with disease severity, with more positive cells present in the later stages of liver damage (81.8% vs 18.2%). Furthermore, bile plugs were mainly found in CD56-positive immature biliary ducts. Notch signaling was a key regulatory pathway in biliary duct formation and played a role in tissue fibrosis. Notch1 was co-expressed in CD56-positive cells, whereas Notch2 was found exclusively in blood vessels in the portal area of patients with BA.
CONCLUSION: The maturation of biliary epithelial cells and the expression of Notch may play a role in the pathogenesis of BA.
Core tip: Clinical laboratory parameters did not correlate with tissue fibrosis in patients with biliary atresia (BA). Immunohistochemical staining showed that CD56-positive immature bile ducts were present only in patients with BA but not in those with choledochal cyst or neonatal hepatitis. The number of CD56 expressing cells correlated with disease severity, with more positive cells present in the later stages of liver damage. Furthermore, the signaling molecule Notch1, but not Notch2, was co-expressed in CD56 positive cells. Our data provide new insights into the pathogenesis of BA in terms of biliary epithelial cell maturation and Notch expression.