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.