Glantz Anna, Reilly Sarah-Jayne, Benthin Lisbet, Lammert Frank, Mattsson Lars-Ake, Marschall Hanns-Ulrich
Department of Obstetrics and Gynaecology, Sahlgrenska University Hospital/East, Gothenburg, Sweden.
Hepatology. 2008 Feb;47(2):544-51. doi: 10.1002/hep.21987.
Intrahepatic cholestasis of pregnancy (ICP) is characterized by pruritus, elevated bile acids, and, specifically, elevated disulphated progesterone metabolites. We aimed to study changes in these parameters during treatment with dexamethasone or ursodeoxycholic acid (UDCA) in 40 out of 130 women included in the Swedish ICP intervention trial (26 randomized to placebo or UDCA, 14 randomized to dexamethasone). Serum bile acid profiles and urinary steroid hormone metabolites were analyzed using isotope-dilution gas chromatography-mass spectrometry and electrospray-mass spectrometry. We found that all patients displayed ICP-typical serum bile acid profiles with >50% cholic acid at baseline but almost 80% UDCA upon treatment with this bile acid. In UDCA-treated patients, relative amounts of disulphated progesterone metabolites in urine decreased by 34%, 48% (P < 0.05), and 55% (P < 0.05) after 1, 2, and 3 weeks of treatment, respectively, which was significantly correlated to improvements of pruritus scores but not to serum bile acid levels. In contrast, in patients randomized to dexamethasone or placebo, no changes in steroid metabolites or pruritus scores were observed.
UDCA treatment in ICP decreased urinary excretion of disulphated progesterone metabolites, suggesting that amelioration of pruritus is connected to stimulation of hepatobiliary excretion of progesterone disulphates.
妊娠期肝内胆汁淤积症(ICP)的特征为瘙痒、胆汁酸升高,特别是二硫酸化孕酮代谢产物升高。我们旨在研究瑞典ICP干预试验纳入的130名女性中40名女性在接受地塞米松或熊去氧胆酸(UDCA)治疗期间这些参数的变化(26名随机分配至安慰剂或UDCA组,14名随机分配至地塞米松组)。使用同位素稀释气相色谱 - 质谱联用仪和电喷雾质谱仪分析血清胆汁酸谱和尿类固醇激素代谢产物。我们发现所有患者在基线时均表现出ICP典型的血清胆汁酸谱,胆酸含量>50%,但在用这种胆汁酸治疗后UDCA含量接近80%。在接受UDCA治疗的患者中,治疗1、2和3周后,尿中二硫酸化孕酮代谢产物的相对含量分别下降了34%、48%(P<0.05)和55%(P<0.05),这与瘙痒评分的改善显著相关,但与血清胆汁酸水平无关。相比之下,在随机分配至地塞米松或安慰剂组的患者中,未观察到类固醇代谢产物或瘙痒评分的变化。
ICP患者接受UDCA治疗可降低尿中二硫酸化孕酮代谢产物的排泄,提示瘙痒的改善与刺激孕酮二硫酸盐的肝胆排泄有关。