Bile acid pool dynamics in progressive familial intrahepatic cholestasis with partial external bile diversion.
OBJECTIVE
Partial external bile diversion (PEBD) is an established therapy for low-γ-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 19.5, 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 (r2 = 0.760, P = 0.024) and CDCA (r2 = 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.
*Department of Pediatrics, Comer Children's Hospital, University of Chicago †Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL ‡Department of Pediatric Gastroenterology, University of Groningen, Beatrix Children's Hospital-University Medical Center, Groningen, The Netherlands §Institute of Liver Studies, King's College Hospital, London, UK ||Department of Pediatrics, Children's Hospital of Pittsburgh, Pittsburgh, PA.
Hilary S
HS
Jericho
Elizabeth
E
Kaurs
Renze
R
Boverhof
Alex
A
Knisely
Benjamin L
BL
Shneider
Henkjan J
HJ
Verkade
Peter F
PF
Whitington
D000293:Adolescent; D000328:Adult; D001647:Bile Acids and Salts / Q000097:blood / Q000378:metabolism*; D001648:Bile Canaliculi / Q000378:metabolism / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000601:surgery; D002648:Child; D002675:Child, Preschool; D002768:Choledochostomy / Q000009:adverse effects*; D002780:Cholestasis, Intrahepatic / Q000097:blood / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D003903:Deuterium; D005260:Female; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007223:Infant; D007583:Jejunum / Q000601:surgery; D007700:Kinetics; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D016031:Liver Transplantation / Q000009:adverse effects; D008297:Male; D011865:Radioisotope Dilution Technique; D055815:Young Adult
D001647:Bile Acids and Salts; D003903:Deuterium