Brites D, Rodrigues C M, Oliveira N, Cardoso M, Graça L M
Centro de Patogénese Molecular, Faculdade de Farmácia da Universidade de Lisboa, Portugal.
J Hepatol. 1998 Jan;28(1):91-8. doi: 10.1016/s0168-8278(98)80207-9.
BACKGROUND/AIMS: Intrahepatic cholestasis of pregnancy is characterized by pruritus and increased levels of serum bile acids, and is often associated with premature delivery, fetal distress, and perinatal mortality. The aims of the present study were: (i) to better define the serum bile acid profile in intrahepatic cholestasis of pregnancy and its potential usefulness for differential diagnosis; (ii) to investigate the effect of ursodeoxycholic acid treatment on the bile acid pool; and (iii) to investigate possible adverse effects of therapy.
Fifteen patients with intrahepatic cholestasis of pregnancy were enrolled in this study. Ursodeoxycholic acid (14 mg/kg body weight per day) was administered for 13 +/- 5 days. Twenty normal pregnant women served as controls. Serum bile acid profile was analyzed by high-performance liquid chromatography.
Patients with cholestasis of pregnancy showed significant alterations in the proportion of primary bile acids, with an increase in cholic acid (64.0 +/- 3.0% vs. 32.2 +/- 1.8%, p < 0.01), and a decrease in chenodeoxycholic acid (20.8 +/- 1.4% vs. 31.9 +/- 1.3%, p < 0.01), as compared to controls, resulting in a marked elevation in the cholic/chenodeoxycholic acid ratio (3.4 +/- 0.5 vs. 1.1 +/- 0.1, p < 0.01). The glycine/taurine ratio was reduced in cholestasis of pregnancy (0.8 +/- 0.1 vs. 1.4 +/- 0.1, p < 0.01). During ursodeoxycholic acid administration its proportion in serum increased from 1.4 +/- 0.6% (0.6 +/- 0.2 micromol/l) at baseline to 24.7 +/- 2.3% (5.9 +/- 1.9 micromol/l) with therapy (p < 0.01). This increment was accompanied by a significant decrease in the percentage of cholic acid (28.2 +/- 2.6%, p < 0.01) and an elevation in chenodeoxycholic acid proportion (25.0 +/- 1.9%, N.S.). Although lithocholic acid concentration in serum was maintained with treatment (1.2 +/- 0.2 micromol/l vs. 1.7 +/- 0.5 micromol/l), there was a significant increase in lithocholic acid proportion (p < 0.01) from 3.3 +/- 0.5% at baseline to 7.4 +/- 1.3% during therapy. The glycine/taurine ratio of serum bile acid pool returned to normal after ursodeoxycholic acid administration (1.7 +/- 0.3).
These results establish the importance of ursodeoxycholic acid treatment for the correction of maternal serum bile acid profile in cholestasis of pregnancy, indicating that ursodeoxycholic acid may improve fetal prognosis.
背景/目的：妊娠期肝内胆汁淤积症的特征为瘙痒和血清胆汁酸水平升高，且常与早产、胎儿窘迫及围产期死亡率相关。本研究的目的为：（i）更好地明确妊娠期肝内胆汁淤积症的血清胆汁酸谱及其在鉴别诊断中的潜在用途；（ii）研究熊去氧胆酸治疗对胆汁酸池的影响；（iii）研究治疗可能产生的不良反应。
本研究纳入了15例妊娠期肝内胆汁淤积症患者。给予熊去氧胆酸（每日14mg/kg体重），持续13±5天。20名正常孕妇作为对照。采用高效液相色谱法分析血清胆汁酸谱。
妊娠期胆汁淤积症患者的初级胆汁酸比例有显著改变，与对照组相比，胆酸增加（64.0±3.0%对32.2±1.8%，p<0.01），鹅去氧胆酸减少（20.8±1.4%对31.9±1.3%，p<0.01），导致胆酸/鹅去氧胆酸比值显著升高（3.4±0.5对1.1±0.1，p<0.01）。妊娠期胆汁淤积症患者的甘氨酸/牛磺酸比值降低（0.8±0.1对1.4±0.1，p<0.01）。在给予熊去氧胆酸治疗期间，其在血清中的比例从基线时的1.4±0.6%（0.6±0.2μmol/L）增加至治疗后的24.7±2.3%（5.9±1.9μmol/L）（p<0.01）。这一增加伴随着胆酸百分比的显著降低（28.2±2.6%，p<0.01）和鹅去氧胆酸比例的升高（25.0±1.9%，无显著性差异）。尽管治疗期间血清中石胆酸浓度维持不变（1.2±0.2μmol/L对1.7±0.5μmol/L），但其比例从基线时的3.3±0.5%显著增加至治疗期间的7.4±1.3%（p<0.01）。给予熊去氧胆酸后，血清胆汁酸池的甘氨酸/牛磺酸比值恢复正常（1.7±0.3）。
这些结果证实了熊去氧胆酸治疗对纠正妊娠期胆汁淤积症孕妇血清胆汁酸谱的重要性，表明熊去氧胆酸可能改善胎儿预后。
