Document Detail

Biliary diversion for progressive familial intrahepatic cholestasis: improved liver morphology and bile acid profile.
MedLine Citation:
PMID:  14517804     Owner:  NLM     Status:  MEDLINE    
BACKGROUND AND AIMS: Progressive familial intrahepatic cholestasis (PFIC) is characterized by pruritus, intrahepatic cholestasis, low serum gamma-glutamyltransferase levels, and characteristic "Byler bile" on electron microscopy. Many patients require liver transplantation, but partial external biliary diversion (PEBD) has shown therapeutic promise. However, the effect of PEBD on liver morphology and bile composition has not been evaluated. METHODS: We reviewed liver biopsy specimens from 3 children with low gamma-glutamyltransferase PFIC before and after PEBD. Follow-up liver biopsies were performed 9-60 months after PEBD. Light and electron microscopic features were scored blindly. Biliary bile acid composition was analyzed by gas chromatography-mass spectrometry before and after PEBD in 1 patient and after PEBD in 2 patients. RESULTS: Following PEBD, all patients improved clinically. Preoperative biopsy specimens showed characteristic features of PFIC, including portal fibrosis, chronic inflammation, cholestasis, giant cell transformation, and central venous mural sclerosis. Ultrastructural findings included coarse, granular canalicular Byler bile, effaced canalicular microvilli, and proliferative pericanalicular microfilaments. Following diversion, histology showed almost complete resolution of cholestasis, portal fibrosis, and inflammation with resolution of ultrastructural abnormalities. Biliary bile acids before PEBD consisted predominantly of cholic acid. After PEBD, the proportion of chenodeoxycholic acid increased significantly in 1 patient and was above the PFIC range in a second patient. CONCLUSIONS: The resolution of hepatic morphologic abnormalities following PEBD supports PEBD as an effective therapy for PFIC. The improved biliary bile acid composition suggests enhanced bile acid secretion after PEBD, perhaps by induction of alternative canalicular transport proteins.
Amethyst C Kurbegov; Kenneth D R Setchell; Joel E Haas; Gary W Mierau; Michael Narkewicz; John D Bancroft; Frederick Karrer; Ronald J Sokol
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Publication Detail:
Type:  Case Reports; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Gastroenterology     Volume:  125     ISSN:  0016-5085     ISO Abbreviation:  Gastroenterology     Publication Date:  2003 Oct 
Date Detail:
Created Date:  2003-09-30     Completed Date:  2003-10-30     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0374630     Medline TA:  Gastroenterology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1227-34     Citation Subset:  AIM; IM    
Pediatric Liver Center and Liver Transplantation Program, Department of Pediatrics, University of Colorado School of Medicine and The Children's Hospital, Denver, Colorado, USA.
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MeSH Terms
Bile Acids and Salts / analysis,  biosynthesis*
Biliary Tract Surgical Procedures*
Child, Preschool
Cholestasis, Intrahepatic / metabolism,  pathology*,  surgery*
Gas Chromatography-Mass Spectrometry
Liver / metabolism*,  pathology*,  ultrastructure
Microscopy, Electron, Scanning
gamma-Glutamyltransferase / blood
Grant Support
Reg. No./Substance:
0/Bile Acids and Salts; EC

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