SECRETION AND COMPOSITION OF BILE AFTER HUMAN LIVER-TRANSPLANTATION -STUDIES ON THE EFFECTS OF CYCLOSPORINE AND TACROLIMUS

Cyclosporine (CsA) and tacrolimus (FR506) have recently been reported to inhibit canalicular transport of bile acids in vitro and thereby po ssibly induce cholestasis. A relative reduction of chenodeoxycholic ac id (CDCA) has been observed after liver transplantation when CsA is us ed as immunosuppressant. We tested the hypothesis that CsA induces cho lestasis and reduces CDCA secretion as compared with treatment with mo noclonal antibodies (OKT3), and that CsA differs from FK506 with regar d to its effects on biliary lipid secretion. Bile flow, biliary lipid secretion rates, and biliary bile acid composition were determined dur ing the first 10 days after transplantation in 29 liver transplant rec ipients, Two prospective randomized studies were performed that compar ed CsA and OKT3 and compared CsA- and FR506-based regimens, In study 1 , bile acid output averaged 0.75+/-0.15 mu mol/min in the CsA I group and 0.54+/-0.11 mu mol/min in the OKT3 group on postoperative day 1, B ile flow and bile acid output then increased, and there was no signifi cant difference between the two groups. The relative proportion of CDC A decreased to the same extent in both groups. In study 2, mean bile a cid outputs on postop erative day 1 were 0.57+/-0.26 mu mol/min and 0. 55+/-0.15 mu mol/min in the CsA 2 and FK506 groups, respectively, The following increase in bile acid secretion was significantly larger in the FK506 group. After transplantation, the relative proportion of CDC A decreased with time in both groups, but the reduction was more rapid in the FK506 group. In conclusion, CsA did not inhibit bile secretion during short-term treatment after liver transplantation. Compared wit h patients given CsA-based treatment, patients with FK506-based treatm ent recovered bile secretion more rapidly.