Enterohepatic cycling of bilirubin: a putative mechanism for pigment gallstone formation in ileal Crohn's disease.
OBJECTIVE
Patients with ileal disease, bypass, or resection are at increased risk for developing gallstones. In ileectomized rats, bilirubin secretion rates into bile are elevated, most likely caused by increased colonic bile salt levels, which solubilize unconjugated bilirubin, prevent calcium complexing, and promote its absorption and enterohepatic cycling. The hypothesis that ileal disease or resection engenders the same pathophysiology in humans was tested.


METHODS
Sterile gallbladder bile samples were obtained intraoperatively from 29 patients with Crohn's disease and 19 patients with ulcerative colitis. Bilirubin, total calcium, biliary lipids, beta-glucuronidase activities, and cholesterol saturation indices in bile were measured, and markers of hemolysis and ineffective erythropoiesis in blood were assessed.


RESULTS
Bilirubin conjugates, unconjugated bilirubin, and total calcium levels were increased 3-10-fold in bile of patients with ileal disease and/or resection compared with patients with Crohn's colitis or ulcerative colitis. Biliary bilirubin concentrations correlated positively with the anatomic length and duration of ileal disease. Endogenous biliary beta-glucuronidase activities were comparable in all groups, and both the hemogram and serum vitamin B12 levels were normal.


CONCLUSIONS
This study establishes that increased bilirubin levels in bile of patients with Crohn's disease are caused by lack of functional ileum, supporting the hypothesis that enterohepatic cycling of bilirubin occurs.
Brink
M A
MA
Department of Gastrointestinal and Liver Diseases, Academic Medical Center, Amsterdam, The Netherlands. M.A.BRINK@amc.uva.nl
Slors
J F
JF
Keulemans
Y C
YC
Mok
K S
KS
De Waart
D R
DR
Carey
M C
MC
Groen
A K
AK
Tytgat
G N
GN
D000328:Adult; D001646:Bile / Q000378:metabolism; D001654:Bile Pigments / Q000378:metabolism*; D001663:Bilirubin / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002769:Cholelithiasis / Q000209:etiology* / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D003424:Crohn Disease / Q000097:blood / Q000150:complications* / Q000378:metabolism; D003460:Crystallization; D004764:Enterohepatic Circulation / Q000502:physiology*; D005260:Female; D005704:Gallbladder / Q000378:metabolism; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D007077:Ileal Diseases / Q000097:blood / Q000150:complications* / Q000378:metabolism; D050356:Lipid Metabolism; D008297:Male; D008875:Middle Aged; D014805:Vitamin B 12 / Q000097:blood
D001654:Bile Pigments; D002784:Cholesterol; D005966:Glucuronidase; D014805:Vitamin B 12; D001663:Bilirubin; D002118:Calcium