Dr Lizemarie Wium1
1King's College Hospital Nhs Trust, London, United Kingdom, 2Imperial College London, London, United Kingdom, 3Mirum Pharmaceuticals, Foster City, United States of America
Biography:
Lizemarie trained and worked as a a general physician and obstetric physician at the University of Pretoria, South Africa before becoming the current lead obstetric physician at King’s College Hospital NHS Foundation Trust, London. She has a special interest in women with previous or current severe cholestasis in pregnancy.
Abstract:
Intrahepatic Cholestasis of pregnancy (ICP) is the commonest pregnancy-specific liver condition. The etiology is multifactorial, including environmental, hormonal, and genetic factors. Women with ICP have elevated serum bile acid concentrations (hypercholanaemia) and an increased risk of preterm birth and stillbirth; the stillbirth risk increases threefold when serum bile acids rise above 100umol/L. A likely explanation is maternal (and fetal) hypercholanaemia-induced fetal cardiac arrhythmia. The first line management of ICP is ursodeoxycholic acid (UDCA). A meta-analysis of 6,974 ICP cases concluded that UDCA protected against stillbirth and preterm birth with a number needed to treat of 15. Maralixibat (MRX) is an ileal bile acid transport (IBAT) inhibitor that prevents the enterohepatic recirculation of bile acids, thereby lowering maternal serum bile acid concentrations. MRX has successfully been used in patients with Alagille syndrome, progressive familial intrahepatic cholestasis and primary sclerosing cholangitis, effectively reducing itch and serum bile acids by up to >75%.
We present a 37yr woman, G3P2M1, with recurrent severe ICP after a stillbirth at 36 weeks in her first pregnancy. Investigations for secondary causes of cholestasis and potential underlying liver disease identified gallbladder polyps, the largest measuring 6.6mm, and a heterozygous p.(Val444Ala) ABCB11 genetic variant, consistent with twice the risk of developing ICP compared to the general population. Despite starting UDCA prior to conception, her non-fasting bile acids (NFBAs) reached 118umol/L at 17 weeks. Therefore she was additionally managed with MRX to control hypercholanaemia, the dose was increased at regular intervals (providing no significant diarrhoea) to 175ug/kg/day. Following MRX treatment her NFBAs reduced to below 40umol/L. She had a planned caesarian section at 35+5 weeks gestation and delivered a healthy baby boy, weighing 2.455kg.
In summary, IBAT inhibitors are a new therapy with the potential to improve hypercholanaemia, and therefore the risk of adverse pregnancy outcome, in ICP.
Keywords
intrahepatic cholestasis in pregnancy, IBAT inhibitors
References
1. Pataia V, Dixon PH, Williamson C. Pregnancy and bile acid disorders. American Journal of Physiology-Gastrointestinal and Liver Physiology. 2017;313(1):G1-G6.
2. Ovadia C, Sajous J, Seed PT, Patel K, Williamson NJ, Attilakos G, et al. Ursodeoxycholic acid in intrahepatic cholestasis of pregnancy: a systematic review and individual participant data meta-analysis. Lancet Gastroenterol Hepatol. 2021;6(7):547-58.
3. Gonzales E, Hardikar W, Stormon M, Baker A, Hierro L, Gliwicz D, et al. Efficacy and safety of maralixibat treatment in patients with Alagille syndrome and cholestatic pruritus (ICONIC): a randomised phase 2 study. Lancet. 2021;398(10311):1581-92.