Sonic hedgehog (SHH) and glioblastoma-2 (Gli-2) expressions are associated with poor jaundice-free survival in biliary atresia.
OBJECTIVE
Biliary atresia (BA) causes biliary obstruction in neonates. Although the Kasai operation can successfully treat certain BA cases, many patients exhibit recurrent jaundice and secondary biliary cirrhosis requiring liver transplantation. Consequently, studies of the prognostic factors of the Kasai operation are needed. Accordingly, sonic hedgehog (SHH) pathway expression at the extrahepatic bile duct (EHBD), an important bile duct repair mechanism, will be investigated via immunohistochemistry in patients with BA to examine the association with post-Kasai operation prognosis.


METHODS
Fifty-seven EHBD specimens were obtained during Kasai operations from 1992 to 2009. The SHH, patched (PTCH), and glioblastoma-2 (Gli-2) immunohistochemical staining results were analyzed quantitatively.


RESULTS
Overall, 57.9% of patients had bile flow normalization after the Kasai operation; 43.1% did not. High preoperative serum total bilirubin, direct bilirubin, and aspartate aminotransferase levels were associated with sustained jaundice post-Kasai operation, as was an age ≥65days at the time of surgery (all p<0.05). High Gli-2 and SHH expression rates were significantly associated with early post-Kasai operation jaundice relapse.


CONCLUSIONS
Strong Gli-2 and SHH expression in the EHBD might be a poor prognostic factor in Kasai operation-treated patients with BA.
Department of Pathology, Soonchunhyang University, Cheonan Hospital, Cheonan, Korea.
Hae Yoen
HY
Jung
Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
Jin
J
Jing
Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
Kyoung Bun
KB
Lee
Department of Pathology, Seoul National University College of Medicine, Seoul, Korea. Electronic address: tripj@snu.ac.kr.
Ja-June
JJ
Jang
D001656:Biliary Atresia / Q000150:complications / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D053823:Hedgehog Proteins / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D007565:Jaundice / Q000209:etiology / Q000378:metabolism*; D051741:Kruppel-Like Transcription Factors / Q000096:biosynthesis*; D008297:Male; D009687:Nuclear Proteins / Q000096:biosynthesis*; D011379:Prognosis; D012189:Retrospective Studies; D000075746:Zinc Finger Protein Gli2
D015415:Biomarkers; C082593:GLI2 protein, human; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D009687:Nuclear Proteins; C509239:SHH protein, human; D000075746:Zinc Finger Protein Gli2
Biliary atresia; Glioblastoma-2 (Gli-2); Jaundice free survival (JFS); Kasai operation; Sonic hedgehog (SHH)