CYCLOSPORINE A-MEDIATED CHOLESTASIS IN PATIENTS WITH CHRONIC HEPATITIS AFTER HEART-TRANSPLANTATION

Viral chronic hepatitis often occurs in heart transplant recipients re ceiving cyclosporin. This essential immunosuppressive drug may induce cholestasis. We investigated the effect of treatment with cyclosporin on serum conjugated bile acids in patients with chronic hepatitis deve loping after heart transplantation. Fifty-nine patients were studied: 17 with chronic hepatitis, 15 heart transplant patients with normal al anine aminotransferase activity, and 27 heart transplant patients with chronic hepatitis, the last two groups receiving cyclosporin. Hepatic biochemical tests and total bile acid concentration were determined o n fasting blood samples. The individual glyco- and tauroconjugated bil e acids were quantified by high-performance liquid chromatography and direct spectrometry. In patients taking cyclosporin the bilirubin conc entration and the alkaline phosphatase activity were increased only wh en hepatitis was present, in association with a slight increase in cho lic acid level (5.13 mu M vs 0.68 mu M; P < 0.01). Conjugated lithocho late concentration was dramatically higher when hepatitis and immunosu ppression with cyclosporin were associated (1.17 mu M vs. 0.03 and 0.0 4 mu M; P < 0.01). Chenodeoxycholate was the main circulating bile aci d only in the heart transplant patients treated with cyclosporin but w ithout hepatitis. These results suggest that the mechanisms which expl ain the cyclosporin-associated modifications of the bile acid pool are different according to the presence or absence of hepatitis. The occu rrence of hepatitis in patients on cyclosporin led to an increase in s erum lithocholate and primary bile acid concentrations. Further studie s are required to assess the effect of ursodeoxycholic acid for this c holestasis.