Myara A, Cadranel J F, Dorent R, Lunel F, Bouvier E, Gerhardt M, Bernard B, Ghoussoub J J, Cabrol A, Gandjbakhch I, Opolon P, Trivin F
Department of Biochimie, Hôpital Saint-Joseph, Paris, France.
Eur J Gastroenterol Hepatol. 1996 Mar;8(3):267-71. doi: 10.1097/00042737-199603000-00015.
Viral chronic hepatitis often occurs in heart transplant recipients receiving 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 developing after heart transplantation. Fifty-nine patients were studied: 17 with chronic hepatitis, 15 heart transplant patients with normal alanine 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 on fasting blood samples. The individual glyco- and tauroconjugated bile acids were quantified by high-performance liquid chromatography and direct spectrometry. In patients taking cyclosporin the bilirubin concentration and the alkaline phosphatase activity were increased only when hepatitis was present, in association with a slight increase in cholic acid level (5.13 microM vs. 0.68 microM; P < 0.01). Conjugated lithocholate concentration was dramatically higher when hepatitis and immunosuppression with cyclosporin were associated (1.17 microM vs. 0.03 and 0.04 microM; P < 0.01). Chenodeoxycholate was the main circulating bile acid only in the heart transplant patients treated with cyclosporin but without hepatitis. These results suggest that the mechanisms which explain the cyclosporin-associated modifications of the bile acid pool are different according to the presence or absence of hepatitis. The occurrence of hepatitis in patients on cyclosporin led to an increase in serum lithocholate and primary bile acid concentrations. Further studies are required to assess the effect of ursodeoxycholic acid for this cholestasis.
病毒性慢性肝炎常发生于接受环孢素治疗的心脏移植受者。这种重要的免疫抑制药物可能会诱发胆汁淤积。我们研究了环孢素治疗对心脏移植后发生慢性肝炎患者血清结合胆汁酸的影响。共研究了59例患者：17例慢性肝炎患者，15例丙氨酸转氨酶活性正常的心脏移植患者，以及27例慢性肝炎的心脏移植患者，后两组患者接受环孢素治疗。对空腹血样进行肝脏生化检查和总胆汁酸浓度测定。通过高效液相色谱法和直接光谱法对个体的甘氨胆酸和牛磺胆酸结合胆汁酸进行定量分析。在服用环孢素的患者中，仅当存在肝炎时胆红素浓度和碱性磷酸酶活性才会升高，同时胆酸水平略有升高（5.13微摩尔/升对0.68微摩尔/升；P<0.01）。当肝炎与环孢素免疫抑制同时存在时，结合型石胆酸浓度显著更高（1.17微摩尔/升对0.03和0.04微摩尔/升；P<0.01）。鹅去氧胆酸仅在接受环孢素治疗但无肝炎的心脏移植患者中是主要的循环胆汁酸。这些结果表明，根据是否存在肝炎，解释环孢素相关胆汁酸池改变的机制有所不同。服用环孢素的患者发生肝炎会导致血清石胆酸和初级胆汁酸浓度升高。需要进一步研究来评估熊去氧胆酸对这种胆汁淤积的影响。
