Possible role of a defect in hepatic bilirubin glucuronidation in the initiation of cholesterol gallstones.
Abnormally low activity of hepatic bilirubin UDP-glucuronosyltransferase was found in 25% of 81 unselected patients with gallstones, as compared with only 3% in 35 controls. At the time of cholecystectomy, the stones were taken for analysis in 48 of 81 patients, and a bile sample was obtained in 42 of them. Among the stones, 75% were cholesterol stones, 15% pigment stones, and 10% 'intermediate' stones. Low hepatic conjugating activity was not preferentially associated with a given type of stone. No relation was found between the enzymic deficiency and the biliary cholesterol saturation index. A high proportion of biliary bilirubin monoglucuronide (over 40%) was found in four of seven patients with low transferase activity, as was earlier demonstrated in patients with overt Gilbert's syndrome. Raised biliary bilirubin monoglucuronide was also found in three patients, out of 46, who had normal transferase but raised biliary beta-glucuronidase activity. There was no evidence that deficient bilirubin conjugation could be a consequence of gallstones: the activity of another hepatic microsomal enzyme, glucose 6-phosphatase, taken as a reference, was measured in 12 patients and was always normal. Taking into account the very high frequency of a bilirubin centre in the cholesterol stones (87% of the cases in the present series), it is suggested that the increased proportion in poorly soluble biliary bilirubin monoglucuronide, which was associated with defective conjugation, could act as a trigger for gallstone initiation, regardless of the final composition of the stone.
D000293:Adolescent; D000328:Adult; D000368:Aged; D001646:Bile / Q000378:metabolism; D001663:Bilirubin / Q000378:metabolism*; D002769:Cholelithiasis / Q000209:etiology* / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D005260:Female; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
D002784:Cholesterol; D014453:Glucuronosyltransferase; D005952:Glucose-6-Phosphatase; D001663:Bilirubin