New treatment target on the horizon for stillbirth and liver problems

A new discovery by researchers suggests a possible new target for treating a serious complication of pregnancy called obstetric cholestasis.

Obstetric cholestasis is a liver condition, which causes a build-up of toxic bile acids in the bloodstream. It occurs in one in 140 pregnancies in the UK and can result in stillbirth.

Funded by the children’s charity Action Medical Research, Imperial College London researchers studied the proteins that control the levels of bile acids in the blood. The results should aid the development of treatments for the condition and help doctors to predict and minimise the risk of fatal consequences for the unborn baby.

The levels of certain hormones in the body are particularly high during pregnancy. Women who suffer with obstetric cholestasis are thought to have an accumulation of the breakdown products of these hormones which reduces the body’s ability to remove bile from the liver. Sufferers experience severe itching especially on the hands and feet, from around week 28 of pregnancy.

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 obstetric cholestasis 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 new research, published in the journal Hepatology, found that in women with the condition, raised levels of substances linked with pregnancy hormones interfere with FXR – a protein in liver cells. This affects he way that FXR senses and controls bile acid levels.

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

Researchers hope that new drugs targeting FXR could reduce the risk of complications to the baby, by lowering the levels of bile acids in the mother.

Co-researcher Dr Shadi Abu-Hayyeh said: “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 obstetric cholestasis.”

The study was also supported by Genesis Research Trust, Lauren Page Trust, the NIHR Imperial Biomedical Research Centre and the Wellcome Trust.

Adapted from a press release from Action Medical Research.

Reference

S Abu-Hayyeh et al. 'Intrahepatic cholestasis of pregnancy levels of sulfated progesterone metabolites inhibit farnesoid X receptor resulting in a cholestatic phenotype.' Hepatology Volume 57, Issue 2, pages 716–726, February 2013