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Clinicopathologic implications of sonic hedgehog pathway activation on remnant extrahepatic bile duct of biliary atresia

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Authors
정혜연
Advisor
장자준
Major
의학과
Issue Date
2012-02
Publisher
서울대학교 대학원
Description
학위논문 (석사)-- 서울대학교 대학원 : 의학과, 2012. 2. 장자준.
Abstract
Background Biliary atresia (BA) is the inflammatory disease of extrahepatic bile ducts accompanied with variable degree of fibrosis. Recently Hedgehog (Hh) pathway has been suggested as the main pathway involving the reparative mechanisms, but the prognostic significance still remains unclear.
Aims We here sought to describe the way of HH signaling acting on the remnant extrahepatic bild duct (EHBD) and the prognostic significance of activated Hh signaling in BA by immunohistochemistry.
Materials and Methods A sample of 57 patients with biliary atresia was evaluated in a retrospective study. Their histologic specimens were stained for PTCH, SHH and Gli-2 through immunohistochemistry in order to study biliary structures. The relationship between the patients prognosis, histopathologic classification and immunohistochemical results were analyzed.
Results A total of twenty-two out of 57 (38.59%) patients had failed to normalize serum bilirubin level, or failed Kasai operation. These patients demonstrated lower positive rate of SHH and Gli-2 expression on their peribiliary glands (PBGs); 0% and 45.8%, respectively, while patients with successful Kasai operation had higher positive rate; SHH and Gli-2 expression rate 71.1% and 75.0%, respectively (p<0.05). Liver transplantation (LT) had performed in 64.91% of patients after Kasai operation. 2-year survival rate of native liver was 14.3% and 37.7% in patients whose PBG showed negative for SHH and Gli-2, while 46.7% and 49.5% in patients whose PBG showed positive for SHH and Gli-2 (p<0.05). Additionally, successful Kasai operation, Kasai operation in younger age (<65), low postoperative liver function test results were also associated with better overall survival (OS) of native liver. In multivariate analysis, it was the Gli-2 expression and postoperative AST and ALT level that was related with OS of native liver.
Conclusion Activated SHH signaling pathway on PBG would be the predictive marker of short-term and long-term outcome after Kasai operation in BA patients.
Language
eng
URI
https://hdl.handle.net/10371/155341

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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Medicine (의학과)Theses (Master's Degree_의학과)
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