Bg. Ericzon et al., SECRETION AND COMPOSITION OF BILE AFTER HUMAN LIVER-TRANSPLANTATION -STUDIES ON THE EFFECTS OF CYCLOSPORINE AND TACROLIMUS, Transplantation, 63(1), 1997, pp. 74-80
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.