Combes B, Carithers R L, Maddrey W C, Munoz S, Garcia-Tsao G, Bonner G F, Boyer J L, Luketic V A, Shiffman M L, Peters M G, White H, Zetterman R K, Risser R, Rossi S S, Hofmann A F
University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA.
Hepatology. 1999 Jun;29(6):1649-54. doi: 10.1002/hep.510290618.
Bile acid composition in fasting duodenal bile was assessed at entry and at 2 years in patients with primary biliary cirrhosis (PBC) enrolled in a randomized, double-blind, placebo-controlled trial of ursodeoxycholic acid (UDCA) (10-12 mg/kg/d) taken as a single bedtime dose. Specimens were analyzed by a high-pressure liquid chromatography method that had been validated against gas chromatography. Percent composition in bile (mean +/- SD) for 98 patients at entry for cholic (CA), chenodeoxycholic (CDCA), deoxycholic (DCA), lithocholic (LCA), and ursodeoxycholic (UDCA) acids, respectively, were 57.4 +/- 18.6, 31.5 +/- 15.5, 8.0 +/- 9.3, 0.3 +/- 1.0, and 0.6 +/- 0.9. Values for CA were increased, whereas those for CDCA, DCA, LCA, and UDCA were decreased when compared with values in normal persons. Bile acid composition of the major bile acids did not change after 2 years on placebo medication. By contrast, in patients receiving UDCA for 2 years, bile became enriched with UDCA on average to 40.1%, and significant decreases were noted for CA (to 32.2%) and CDCA (to 19.5%). No change in percent composition was observed for DCA and LCA. Percent composition at entry and changes in composition after 2 years on UDCA were similar in patients with varying severity of PBC. In patients whose bile was not enriched in UDCA (entry and placebo-treated specimens), CA, CDCA, DCA, and the small amount of UDCA found in some of these specimens were conjugated to a greater extent with glycine (52%-64%) than with taurine (36%-48%). Treatment with UDCA caused the proportion of all endogenous bile acids conjugated with glycine to increase to 69% to 78%, while the proportion conjugated with taurine (22%-31%) fell (P <.05). Administered UDCA was also conjugated predominantly with glycine (87%).
在一项随机、双盲、安慰剂对照的熊去氧胆酸（UDCA）（10 - 12mg/kg/d）单剂睡前服用的试验中，对原发性胆汁性肝硬化（PBC）患者空腹十二指肠胆汁中的胆汁酸成分在入组时和2年后进行了评估。标本采用已通过气相色谱验证的高压液相色谱法进行分析。98例患者入组时胆汁中胆酸（CA）、鹅去氧胆酸（CDCA）、脱氧胆酸（DCA）、石胆酸（LCA）和熊去氧胆酸（UDCA）的百分比组成（均值±标准差）分别为57.4±18.6、31.5±15.5、8.0±9.3、0.3±1.0和0.6±0.9。与正常人相比，CA值升高，而CDCA、DCA、LCA和UDCA值降低。服用安慰剂2年后，主要胆汁酸的胆汁酸组成未发生变化。相比之下，接受UDCA治疗2年的患者，胆汁中UDCA平均富集至40.1%，CA（降至32.2%）和CDCA（降至19.5%）显著降低。DCA和LCA的百分比组成未观察到变化。不同严重程度的PBC患者入组时的百分比组成以及接受UDCA治疗2年后的组成变化相似。在胆汁中未富集UDCA的患者（入组时和接受安慰剂治疗的标本）中，CA、CDCA、DCA以及这些标本中部分发现的少量UDCA与甘氨酸的结合程度（52% - 64%）高于与牛磺酸的结合程度（36% - 48%）。UDCA治疗使所有内源性胆汁酸与甘氨酸结合的比例增加至69%至78%，而与牛磺酸结合的比例（22% - 31%）下降（P <.05）。服用的UDCA也主要与甘氨酸结合（87%）。
