Bile acid pool dynamics in progressive familial intrahepatic cholestasis with partial external bile diversion

Autor: Renze Boverhof, Elizabeth Kaurs, Hilary Jericho, Peter F. Whitington, Alex S Knisely, Henkjan J. Verkade, Benjamin L. Shneider
Přispěvatelé: Center for Liver, Digestive and Metabolic Diseases (CLDM), Lifestyle Medicine (LM)
Rok vydání: 2014
Předmět:
Male
Jejunum
chemistry.chemical_compound
Chenodeoxycholic acid
familial cholestasis
Child
CHOLIC-ACID
Bile acid
Gastroenterology
Progressive familial intrahepatic cholestasis
medicine.anatomical_structure
Liver
Child
Preschool
Female
BILIARY DIVERSION
HEREDITARY CHOLESTASIS
surgical treatment of familial cholestasis
Hydrophobic and Hydrophilic Interactions
FARNESOID-X-RECEPTOR
EXPRESSION
Adult
medicine.medical_specialty
Radioisotope Dilution Technique
Adolescent
medicine.drug_class
Cholestasis
Intrahepatic
Article
Bile Acids and Salts
Young Adult
Cholestasis
Internal medicine
MEMBER 1
medicine
ABCB11 MUTATIONS
Humans
bile acid kinetics
INTRAHEPATIC CHOLESTASIS
business.industry
Bile Canaliculi
Cholic acid
Infant
medicine.disease
Deuterium
Bile Salt Export Pump
KINASE-C ZETA
Liver Transplantation
SALT EXPORT PUMP
Kinetics
Endocrinology
Bile Ducts
Intrahepatic
chemistry
Choledochostomy
Pediatrics
Perinatology and Child Health
Farnesoid X receptor
business
Zdroj: Journal of Pediatric Gastroenterology and Nutrition, 60(3), 368-374. Lippincott Williams and Wilkins
ISSN: 1536-4801
0277-2116
Popis: Objectives: Partial external bile diversion (PEBD) is an established therapy for low-gamma-glutamyl transferase (GGT) progressive familial intrahepatic cholestasis (PFIC). This study sought to determine whether the dynamics of the cholic acid (CA) and chenodeoxycholic acid (CDCA) pools in subjects with low-GGT-PFIC with successful PEBD were equivalent to those achieved with successful liver transplantation (LTX).Methods: The kinetics of CA and CDCA metabolism were measured by stable isotope dilution in plasma samples in 5 subjects with PEBD, all with intact canalicular bile salt export pump expression and compared with subjects with low-GGT-PFIC with successful LTX. Stomal loss of bile acids was measured in subjects with PEBD.Results: The fractional turnover rate for CA in the PEBD group ranged from 0.5 to 4.2/day (LTX group, range 0.2-0.9/day, P = 0.076) and for CDCA from 0.7 to 4.5/day (LTX group 0.3-0.4/day, P = 0.009). The CA and CDCA pool sizes were equivalent between groups; however, pool composition in PEBD was somewhat more hydrophilic. The CA/CDCA ratio in PEBD ranged from 0.9 to 49.5, whereas in LTX it ranged from 0.5 to 2.6. Synthesis rates computed from isotope dilution correlated well with timed output for both CA (r(2) = 0.760, P = 0.024) and CDCA (r(2) = 0.690, P=0.021).Conclusions: PEBD results in bile acid fractional turnover rates greater than LTX, pool sizes equivalent to LTX, and pool composition that is at least as hydrophilic as produced by LTX.
Databáze: OpenAIRE
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