Enterohepatic cycling of bilirubin: A putative mechanism for pigment gallstone formation in ileal Crohn's disease

Background & Aims: 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 col onic bile salt levels, which solubilize unconjugated bilirubin, prevent cal cium complexing, and promote its absorption and enterohepatic cycling, The hypothesis that ileal disease or resection engenders the same pathophysiolo gy in humans was tested. Methods: Sterile gallbladder bile samples were obt ained intraoperatively from 29 patients with Crohn's disease and 19 patient s with ulcerative colitis. Bilirubin, total calcium, biliary lipids, P-gluc uronidase activities, and cholesterol saturation indices in bile were measu red, 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 dise ase and/or resection compared with patients with Crohn's colitis or ulcerat ive colitis. Biliary bilirubin concentrations correlated positively with th e anatomic length and duration of ileal disease. Endogenous biliary P-glucu ronidase activities were comparable in all groups, and both the hemogram an d serum vitamin B-12 levels were normal. Conclusions: This study establishe s that increased bilirubin levels in bile of patients with Crohn's disease are caused by lack of functional ileum, supporting the hypothesis that ente rohepatic cycling of bilirubin occurs.