英国伦敦国王学院Lucy C Chappell研究组分析了熊去氧胆酸与安慰剂对妊娠期肝内胆汁淤积症的影响。 相关论文2019年9月7日发表在《柳叶刀》上。

2015年12月23日至2018年8月7日，研究组在英格兰和威尔士的33医院产科进行了一项双盲、多中心、随机、安慰剂对照试验。共招募了605名孕妇，年龄均在18岁及以上，患有妊娠期肝内胆汁淤积症，孕周为20周至40周6天，单胎或双胎妊娠，胎儿均无致命异常。参与者按1：1随机分为两组，其中305名口服熊去氧胆酸，300名口服安慰剂，直到分娩。

最终熊去氧胆酸组中304名孕妇生下322名婴儿（1人失访），安慰剂组300名孕妇生下318名婴儿。熊去氧胆酸组中有74名（23%）婴儿围产期死亡，安慰剂组中有85名（27%），风险比为0.85。熊去氧胆酸组发生2例严重不良事件，安慰剂组发生6例，但均与治疗无关。

综上，熊去氧胆酸治疗并不能减少妊娠期肝内胆汁淤积症妇女的不良围产结局，对该疗法应重新考虑。

据悉，妊娠期肝内胆汁淤积症的特点是孕妇瘙痒，血清胆汁酸浓度升高，与死胎率、早产和新生儿住院密切相关。熊去氧胆酸广泛用于治疗该病，但缺乏足够的证据基础。

附：英文原文

Title: Ursodeoxycholic acid versus placebo in women with intrahepatic cholestasis of pregnancy (PITCHES): a randomised controlled trial

Author: Lucy C Chappell, Jennifer L Bell, Anne Smith, Louise Linsell, Edmund Juszczak, Peter H Dixon, Jenny Chambers, Rachael Hunter, Jon Dorling, Catherine Williamson, Jim G Thornton, Irshad Ahmed, Rita Arya, Virginia Beckett, Amarnath Bhide, Heather Brown, George Bugg, Helen Cameron, Nishigandh Deole, Madhuchanda Dey, James Dwyer, Leila Fahel, Ruta Gada, Joanna Girling, Anna Haestier, Sean Hughes, Radha Indusekhar, Bryony Jones, Rahila Khan, Alison Kirkpatrick, Ellen Knox, Karen Lincoln, Malcolm MacDougall, Franz Majoko, Karen McIntyre, Muna Noori, Wendy Oakley, Jane Preston, Poornima Ranka, Mumtaz Rashid, Marwan Salloum, Manjula Samyraju, Catharina Schram, Seema Sen, Sophia Stone, Bee Tan

Issue&Volume: Volume 394 Number 10201

Abstract: 

Background

Intrahepatic cholestasis of pregnancy, characterised by maternal pruritus and increased serum bile acid concentrations, is associated with increased rates of stillbirth, preterm birth, and neonatal unit admission. Ursodeoxycholic acid is widely used as a treatment without an adequate evidence base. We aimed to evaluate whether ursodeoxycholic acid reduces adverse perinatal outcomes in women with intrahepatic cholestasis of pregnancy.

Methods

We did a double-blind, multicentre, randomised placebo-controlled trial at 33 hospital maternity units in England and Wales. We recruited women with intrahepatic cholestasis of pregnancy, who were aged 18 years or older and with a gestational age between 20 weeks and 40 weeks and 6 days, with a singleton or twin pregnancy and no known lethal fetal anomaly. Participants were randomly assigned 1:1 to ursodeoxycholic acid or placebo, given as two oral tablets a day at an equivalent dose of 500 mg twice a day. The dose could be increased or decreased at the clinician's discretion, to a maximum of four tablets and a minimum of one tablet a day. We recommended that treatment should be continued from enrolment until the infant's birth. The primary outcome was a composite of perinatal death (in-utero fetal death after randomisation or known neonatal death up to 7 days after birth), preterm delivery (<37 weeks' gestation), or neonatal unit admission for at least 4 h (from birth until hospital discharge). Each infant was counted once within this composite. All analyses were done according to the intention-to-treat principle. The trial was prospectively registered with the ISRCTN registry, number 91918806.

Findings

Between Dec 23, 2015, and Aug 7, 2018, 605 women were enrolled and randomly allocated to receive ursodeoxycholic acid (n=305) or placebo (n=300). The primary outcome analysis included 304 women and 322 infants in the ursodeoxycholic acid group, and 300 women and 318 infants in the placebo group (consent to use data was withdrawn for 1 woman and 2 infants). The primary composite outcome occurred in 74 (23%) of 322 infants in the ursodeoxycholic acid group and 85 (27%) of 318 infants in the placebo group (adjusted risk ratio 0·85 [95% CI 0·62–1·15]). Two serious adverse events were reported in the ursodeoxycholic acid group and six serious adverse events were reported in the placebo group; no serious adverse events were regarded as being related to treatment.

Interpretation

Treatment with ursodeoxycholic acid does not reduce adverse perinatal outcomes in women with intrahepatic cholestasis of pregnancy. Therefore, its routine use for this condition should be reconsidered.

DOI: 10.1016/S0140-6736(19)31270-X

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)31270-X/fulltext