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Treatment of ICP: UDCA

The most commonly used treatment in ICP is a drug called ursodeoxycholic acid (also known as urso, UDCA, Actigall and ursodiol). UDCA is a naturally occurring bile acid that is present in your body in very small amounts. It may sound contradictory that taking an additional bile acid will help, but UDCA is different from the other bile acids. It is most likely that it works by improving the flow of bile and reducing the passage of harmful bile acids across the placenta. Although UDCA is not licensed for use in pregnancy (as is the case for many drugs), it has been widely used in ICP with informed consent and has not been shown to be harmful to either mothers-to-be or unborn babies.

However, the most recent trial on UDCA (PITCHES) showed that it is not of any benefit for the majority of women. You can read what we say about this here.

UDCA

There are still some researchers who believe that UDCA could protect those unborn babies whose mothers have severe ICP, as explained below.

Can UDCA protect your baby?

Some researchers believe that bile acids may affect the baby’s heart by causing very subtle heart arrhythmias (irregular heartbeats) and have conducted experiments to try to show this. They have grown rodent heart cells in a petri-dish in order to study what happens if bile acids are added to the beating heart cells. They found that if a small amount of bile acids are dropped onto the cells they will begin to beat out of time, and after a while they will stop beating altogether. However, they discovered that if they add UDCA before the cells stop beating this can reverse the effect and the heart cells will all start to beat in time again. Of course, experiments in the lab aren’t going to mimic exactly what is happening in the womb, but for the researchers it has been convincing enough to think that bile acids could be the cause of risk and that ursodeoxycholic acid may have some protective properties for the baby. Research is currently being conducted to extend this work further and to find ways to monitor the baby’s heart more effectively in an ICP pregnancy, as current standard CTG machines cannot detect the subtle arrhythmias that may occur in some ICP babies.

Will UDCA improve or get rid of your itch?

PITCH and PITCHES showed that women who take UDCA typically only see a partial improvement in their itch, and some see none at all. Interestingly, although bile acids have been associated with the itching in ICP for many years, more recent studies have identified that two other substances in the blood, lysophosphatidic acid (LPA) and sulfated progesterone metabolites, are also raised in the blood of women with ICP and may be implicated as other links in the cause of the itching. It could be that finding different treatments to reduce these substances may help with the itch.

So should you take UDCA?

Given what we now know about the drug, on balance, we would say probably not (especially if your bile acids are under 40 µmol/L), but if you feel that taking UDCA might help you then talk to your doctor about this. If your bile acids are extremely high and you have seen that there are other drugs that can be tried (such as rifampicin), talk to them about this and perhaps show them some research papers, which you can download here.

References

Ovadia C, Seed PT, Sklavounos A, Geenes V, Di Illio C, Chambers J et al. Association of adverse perinatal outcomes of intrahepatic cholestasis of pregnancy with biochemical markers: results of aggregate and individual patient data meta-analyses. The Lancet 2019; DOI: http://dx.doi.org/10.1016/S0140-6736(18)31877-4.
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Bacq Y, Sentilhes L, Reyes H, Glantz A, Kondrackiene J, Binder T, Nicastri PL, Locatelli A, Floreani A, Hernandez I, Di Martino V. Efficacy of ursodeoxycholic acid in treating intrahepatic cholestasis of pregnancy: a meta-analysis. Gastroenterology 2012; 143: 1492–501 (Note: This paper does not include the results of the PITCH trial.)

Chappell LC, Gurung V, Seed PT, Chambers J, Williamson C, Thornton JG. Ursodeoxycholic acid versus placebo, and early term delivery versus expectant management, in women with intrahepatic cholestasis of pregnancy: semifactorial randomised clinical trial. BMJ 2012; 344 doi: 10.1136/bmj.e3799

Geenes VL, Lim YH, Bowman N, Tailor H, Dixon PH, Chambers J, Brown L, Wyatt-Ashmead J, Bhakoo K, Williamson C. A placental phenotype for intrahepatic cholestasis of pregnancy. Placenta 2011; 32: 1026–32.

Miragoli, M, Sheikh Abdul Kadir, SH, Sheppard, MN, Salvarani, N, Virta, V, Wells, W, Lab, MJ, Nikolaev, VO, Moshkov, A, Hague, WM, Rohr, S, Williamson, W and Gorelik, J. A protective antiarrhythmic role of ursodeoxycholic acid in an in vitro rat model of the cholestatic fetal heart. Hepatology 2011; 54(4): 1282–1292

Schultz F, Hasan A, Alvarez-Laviada A, Miragoli, M, Bhogal N, Wells S, Poulet C, Chambers, J, Williamson C, Gorelik J. The protective effect of ursodeoxycholic acid in an in vitro model of the human fetal heart occurs via targeting cardiac fibroblasts. Progr Biophys Molec Biol 2016; http://dx.doi.org/10.1016/j.pbiomolbio.2016.01.003