Bile acid metabolism and biliary secretion in patients receiving orthotopic liver transplants: Differing effects of cyclosporine and FK 506

Bile acid metabolism and biliary secretion were characterized in the first 2 wk after orthotopic liver transplantation in 15 patients receiving cyclosporine and in five patients receiving FK 506. Analyses were performed on hepatic bile obtained by T-tube drainage; values obtained were compared with literature values for bile samples obtained in patients who had undergone cholecystectomy. Biliary bile acid output, which is equivalent to bile acid biosynthesis from cholesterol, was low (mean ± S.E.M.) and increased with time: day 1, 0.50 ± 0.1 mmol/day; day 3, 0.8 ± 0.1 mmol/day; and day 6, 1.6 ± 0.5 mmol/day. Chenodeoxycholic acid biosynthesis, as percent of total bile acid biosynthesis, was abnormally low in patients receiving cyclosporine (16.2 ± 1.1) but not in patients receiving FK 506 (38.2 ± 4.8) (p < 0.005). Before the T-tube was clamped, the proportion of deoxycholic acid (a secondary bile acid formed by bacterial 7-dehydroxylation of cholic acid) was low in both groups: cyclosporine, 0.4 ± 0.1; FK 506, 4.8 ± 2.5 (p < 0.01). The mean concentration of bile acids in hepatic bile between days 4 and 11 did not differ significantly between groups: cyclosporine, 7.7 ± 1.3 mmol/L; FK 506 4.3 ± 0.7 mmol/L (mean ± S.E.M.). (These values are similar to those reported for patients who have undergone cholecystectomy.) Bile acid-dependent bile flow, expressed as apparent choleretic activity (microliters of bile per micromole of bile acid output), was markedly elevated: in patients receiving cyclosporine the value was 129, and in patients receiving FK 506 the value was 220. (In patients who have undergone cholecystectomy, this value is less than 30.) It is concluded that canalicular secretion of bile acids is markedly decreased in the immediate postoperative period after liver transplantation, whereas bile flow is relatively unimpaired, possibly because of impaired biliary duct function. During this period, administration of cyclosporine but not FK 506 causes a selective reduction in chenodeoxycholic acid biosynthesis, probably attributable to its known inhibition of cholesterol 27-hydroxylase.