Menu

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), PITCHES, the most recent trial of the drug, showed that it is safe for women to take.

However, PITCHES also showed that UDCA did not reduce bile acids or itch for the majority of women in the trial. You can read what we say about this here.

UDCA

But despite these findings some researchers still felt that UDCA was beneficial to take, and the most recent research from Ovadia et al (2021) showed that it can reduce the risk of spontaneous premature birth, particularly for those women with bile acids over 40 µmol/L. There are also some experts in ICP who still 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 that was being conducted to investigate the impact of bile acids on the fetal heart has now been published.

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 are 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?

This is something for you to talk to your doctors about, but given the research to show that UDCA can reduce the risk of spontaneous premature birth, and that it may reduce the itch a little, on balance we would say that it is still worth considering until a better drug can be identified. 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.

Next >  Management of an ICP pregnancy

< Back to About ICP

References

Ovadia C, Sajous J, Seed PT, Patel K, Williamson NJ, Attilakos G, Azzaroli F, Bacq Y, Batsry L, Broom K, Brun-Furrer R, Bull L, Chambers J, Cui Y, Ding M, Dixon PH, Estiù MC, Gardiner FW, Geenes V, Grymowicz M, Günaydin B, Hague WM, Haslinger C, Hu Y, Indraccolo U, Juusela A, Kane SC, Kebapcilar A, Kebapcilar L, Kohari K, Kondrackienė J, Koster MPH, Lee RH, Liu X, Locatelli A, Macias RIR, Madazli R, Majewska A, Maksym K, Marathe JA, Morton A, Oudijk MA, Öztekin D, Peek MJ, Shennan AH, Tribe RM, Tripodi V, Özterlemez NT, Vasavan T, Audris Wong LF, Yinon Y, Zhang Q, Zloto K, Marschall H-U, Thornton J, Chappell LC, Williamson C. Ursodeoxycholic acid in intrahepatic cholestasis of pregnancy: a systematic review and individual participant data meta-analysis. Lancet Gastroenterology & Hepatology 2021; Online 26 April.
https://doi.org/10.1016/S2468-1253(21)00074-1

Vasavan T, Deepak S, Jayawardane IA, Lucchini M, Martin C, Geenes V, Yang J, Lövgren-Sandblom A, Seed PT, Chambers J, Stone S, Kurlak L, Dixon PH, Marschall H-U, Gorelik J, Chappell L, Loughna P, Thornton J, Pipkin FB, Hayes-Gill B, Fifer WP, Williamson C. Fetal cardiac dysfunction in intrahepatic cholestasis of pregnancy is associated with elevated serum bile acid concentrations. J Hepatol 2020; 74(5): 1087–96. https://doi.org/10.1016/j.jhep.2020.11.038.

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.
PDF

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