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.
Because UDCA is still the most commonly used medication for the treatment of ICP it’s worth explaining the reasons why some doctors feel it may be helpful for you and your unborn baby.
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.
A 2009 study (PITCH; Chappell et al. 2012) showed that there was a reduced incidence of meconium staining (when a baby poos in the fluid that surrounds it whilst in the womb) in the women who took UDCA.
Will UDCA improve or get rid of your itch?
Studies have shown that women who take UDCA often only see a partial improvement in their itch, and some see none at all. However, a small number of women reported that it got rid of it completely. Why there is such a variance is not fully understood. 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’ve written about the drug it’s difficult to answer this, but on balance, UDCA does seem to be the better choice of drug to use at the moment. Further trials are needed to establish how useful it is and a large trial (PITCHES) started in 2015 that should finally provide some answers. For the moment the reasons why doctors use it vary and you may want to ask your doctor what their thoughts are about how useful it is. Some doctors believe that UDCA can help protect the unborn ICP baby, but many also only prescribe it because they believe it may help the itch. This is because they want to see clearer scientific evidence that bile acids cause stillbirth (in research terms this is called ‘establishing the mechanism’) and they may not agree that bile acids are a problem. It’s not an unreasonable suggestion, but you can discuss this with them and talk to them about what you want to do.
If you feel that taking UDCA will help you then you can request 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.
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