Stillbirth and liver problems: new treatment target on the horizon | Action Medical Research

Stillbirth and liver problems: new treatment target on the horizon

31 January 2013

Obstetric cholestasis (OC) is a liver condition that occurs during pregnancy in women. It affects about one in 140 pregnancies in the UK, and can result in stillbirth.1,2

Abnormally high levels of substances in the body linked with pregnancy hormones can contribute to the development of OC, by reducing the body’s ability to remove bile from the liver. This results in a build up of toxic bile acids in the bloodstream, causing severe itching especially on the hands and feet, from around week 28 of pregnancy.

Imperial College London-based research, published 1 February 2012 in the journal Hepatology, has discovered a possible new target for treatment of OC.

Professor Catherine Williamson led the investigations, with funding from children’s charity Action Medical Research*, which looked at the proteins that control the levels of bile acids in the blood. The results should help the development of correct treatments for women with the condition, and help doctors predict and minimise the risk of fatal consequences for the unborn baby.

Creams, such as calamine lotion, can provide some relief from itching and there are some medications that can reduce bile salts and ease itching, but it’s not known whether they are safe to take in pregnancy. Women with OC may be offered an induced birth or caesarean section after 37 weeks in an attempt to reduce the risk of complications affecting the baby and the mother.

The results of the research found that in women with OC, raised levels of substances linked with pregnancy hormones interfere with FXR – a protein in liver cells. The way in which FXR senses and controls bile acid levels is affected.

Professor Williamson says, “Our data demonstrate that in OC, certain pregnancy hormones are abnormally raised and can interfere with liver function, giving rise to the symptoms.”

By understanding how raised levels of pregnancy hormone-related substances contribute to the development of OC, a new treatment target called FXR has now been identified. It is hoped that new drugs targeting FXR could reduce the risk of complications to the baby, by lowering the levels of serum bile acids in the mother.

Co-researcher Dr Shadi Abu-Hayyeh says, “These data are exciting not only because they explain how pregnancy can affect the way the liver functions, but also because they identify particular liver molecules that new drugs can target for the treatment of OC.”

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*The study was also supported by Genesis Research Trust, Lauren Page Trust, Biomedical Research Centre at Imperial College Healthcare NHS Trust and The Wellcome Trust.

1. Obstetric cholestasis OCZ/04/11. The British Liver Trust 2011. Reviewed by: C Williamson. Downloaded 10.12.12.
2. Glantz A, Marschall HU, Mattsson LA. Intrahepatic cholestasis of pregnancy: Relationships between bile acid levels and fetal complication rates. Hepatology. 2004 Aug;40(2):467-74.

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