Crosignani A, Podda M, Bertolini E, Battezzati P M, Zuin M, Setchell K D
Department of Internal Medicine, Ospedale S. Paolo, University of Milan, Italy.
Hepatology. 1991 Jun;13(6):1076-83.
Ursodeoxycholic acid was administered to a patient with benign recurrent intrahepatic cholestasis to prevent cholestatic episodes. A detailed study of bile acid metabolism in this patient was carried out in the anicteric and icteric phases before and after ursodeoxycholic acid (750 mg/day) administration. Urinary, biliary and serum bile acids were measured by gas chromatography-mass spectrometry and by high-performance liquid chromatography techniques. During the anicteric phase the daily urinary excretion and serum concentrations of bile acids were within normal ranges, indicating normal hepatic uptake and secretion of bile acids during the cholestasis-free period. Only slight qualitative differences from normal individuals were observed; the relative proportions of deoxycholic acid in the bile and serum were higher, and 12-oxo-lithocholic acid was the predominant urinary bile acid. During the icteric phase a marked increase in the urinary excretion of primary bile acids and C-1, C-2, C-4 and C-6 hydroxylated metabolites was found. Serum bile acid concentrations increased before the rise in bilirubin, suggesting an acute disturbance in bile acid transport at the onset of the cholestatic attack. After ursodeoxycholic acid administration in the anicteric phase, bile became enriched with the exogenous bile acid, but little qualitative change was found in the other metabolites present in the urine, serum or bile during the anicteric or icteric phases. Prolonged administration of ursodeoxycholic acid failed to prevent recurrence of a cholestatic episode, suggesting that in benign recurrent intrahepatic cholestasis, oral ursodeoxycholic acid may be of little benefit in the treatment or prevention of cholestasis despite marked enrichment of the bile acid pool with this hydrophilic bile acid.
对一名良性复发性肝内胆汁淤积患者给予熊去氧胆酸以预防胆汁淤积发作。在给予熊去氧胆酸（750毫克/天）之前和之后的无黄疸期和黄疸期，对该患者的胆汁酸代谢进行了详细研究。通过气相色谱-质谱法和高效液相色谱技术测定尿液、胆汁和血清中的胆汁酸。在无黄疸期，胆汁酸的每日尿排泄量和血清浓度在正常范围内，表明在无胆汁淤积期肝脏对胆汁酸的摄取和分泌正常。仅观察到与正常个体有轻微的定性差异；胆汁和血清中脱氧胆酸的相对比例较高，且12-氧代石胆酸是主要的尿胆汁酸。在黄疸期，发现初级胆汁酸以及C-1、C-2、C-4和C-6羟基化代谢产物的尿排泄量显著增加。血清胆汁酸浓度在胆红素升高之前就升高，提示胆汁淤积发作开始时胆汁酸转运出现急性紊乱。在无黄疸期给予熊去氧胆酸后，胆汁中外源性胆汁酸增多，但在无黄疸期或黄疸期，尿液、血清或胆汁中存在的其他代谢产物几乎没有定性变化。长期给予熊去氧胆酸未能预防胆汁淤积发作的复发，这表明在良性复发性肝内胆汁淤积中，尽管这种亲水性胆汁酸使胆汁酸池显著富集，但口服熊去氧胆酸在治疗或预防胆汁淤积方面可能益处不大。
