Intrahepatic cholestasis of pregnancy

Keywords: gestational cholestasis, intrahepatic cholestasis of pregnancy, obstetric cholestasis


The intrahepatic cholestasis of pregnancy (ICP) is characterized by pruritus in the pregnant and elevated levels of serum bile acids, in addition it is associated with increased obstetric events such as preterm labor, meconium stained amniotic fluid and intrauterine fetal death. Its incidence is variable, being the South American and Asian countries, where the highest rates are reported. There is no known cause, but there are risk factors as well as well-studied genetic defects. The diagnosis should help to its classification, an early onset of ursodeoxycholic acid (UDCA) and a counseling regarding complications and termination of pregnancy.


Download data is not yet available.


Wikström Shemer E, Marschall H, Ludvigsson J, Stephansson O. Intrahepatic cholestasis of pregnancy and associated adverse pregnancy and fetal outcomes: a 12-year population-based cohort study. BJOG: An International Journal of Obstetrics & Gynaecology. 2013;120(6):717-723.

Glantz A, Marschall HU, Mattsson LA. Intrahepatic cholestasis of pregnancy: relationships between bile acid levels and fetal complication rates. Hepatology 2004;40:467–74.

Geenes V, Chappell L, Seed P, Steer P, Knight M, Williamson C. Association of severe intrahepatic cholestasis of pregnancy with adverse pregnancy outcomes: A prospective population-based case-control study. Hepatology. 2014;59(4):1482-1491.

Reyes H. Review: intrahepatic cholestasis. A puzzling disorder of pregnancy. J Gastroenterol Hepatol 1997;12:211-6.

Reyes H, Zapata R, Hernandez I, Gotteland M, Sandoval L, Jirón MI, Palma J, Almuna R, Silva JJ. Is a leaky gut involved in the pathogenesis of intrahepatic cholestasis of pregnancy? Hepatology 2006;43:715-22.

Diken Z, Usta I, Nassar A. A Clinical Approach to Intrahepatic Cholestasis of Pregnancy. American Journal of Perinatology. 2013;31(01):001-008.

Laatikainen T, Tulenheimo A. Maternal serum bile acid levels and fetal distress in cholestasis of pregnancy. Int J Gynaecol Obst 1984;22:91-4.

Berg B, Helm G, Petersohn L, Tryding N. Cholestasis of pregnancy. Clinical and laboratory studies. Acta Obstet Gynecol Scand 1986;65:107-13.

Locatelli A, Roncaglia N, Arreghini A, Bellini P, Vergani P, Ghidini A. Hepatitis C virus infection is associated with a higher incidence of cholestasis of pregnancy. Br J Obstet Gynaecol 1999;106:498-500.

Roncaglia N, Arreghini A, Locatelli A, Bellini P, Andreotti C, Ghidini A. Obstetric cholestasis: outcome with active management. Eur J Obstet Gynecol Reprod Biol 2002;100:167-70.

Abedin P, Weaver JB, Egginton E. Intrahepatic cholestasis of pregnancy: prevalence and ethnic distribution. Ethn Health 1999;4:35-7.

Qi HB, Shao Y, Wu WX, et al. Grading of intrahepatic cholestasis of pregnancy. Zhonghua Fu Chan Ke Za Zhi 2004;39:14–7.

Locatelli A, Roncaglia N, Arreghini A, et al. Hepatitis C virus infection is associated with a higher incidence of cholestasis of pregnancy. Br J Obstet Gynaecol 1999;106:498–500.

Paternoster DM, Fabris F, Palu` G, et al. Intra-hepatic cholestasis of pregnancy in hepatitis C virus infection. Acta Obstet Gynecol Scand 2002;81:99–103.

Ropponen A, Sund R, Riikonen S, et al. Intrahepatic cholestasis of pregnancy as an indicator of liver and biliary diseases: a population-based study. Hepatology 2006;43:723–8.

Marschall H-U, Shemer EW, Ludvigsson JF, et al. Intrahepatic cholestasis of pregnancy and associated hepatobiliary disease: a population based cohort study. Hepatology 2013;58:1385–91.

Berg B, Helm G, Petersohn L, et al. Cholestasis of pregnancy. Clinical and laboratory studies. Acta Obstet Gynecol 1996;175:957–60.

Laatikainen T, Ikonen E. Fetal prognosis in obstetric hepatosis. Ann Chir Gynaecol Fenn 1975;64:155–64.

Reis H, Baez ME, Gonzalez MC, et al. Selenium, zinc and copper plasma levels in intrahepatic cholestasis of pregnancy, in normal pregnancies and in healthy individuals in Chile. J Hepatol 2000;32:542–9.

Reis H, Kauppila A, Korpela H, et al. Low serum selenium concentration and glutathione peroxidase activity in intrahepatic cholestasis of pregnancy. Br Med J 1987;294:150–2.

Wilkstrom Shemer E, Marshall HU. Decreased 1,25 dihydroxy vitamin D levels in women with intrahepatic cholestasis of pregnancy. Acta Obstet Gynecol Scand 2010;89:1420–3.

Gonzales M, Reyes H, Arrese M, et al. Intrahepatic cholestasis of pregnancy in twin pregnancies. J Hepatol 1989;9:84–90.

Rioseco A, Ivankovic M, Manzur A, et al. Intrahepatic cholestasis of pregnancy: a retrospective case-control study of perinatal outcome. Am J Obstet Gynecol 1994;170:890–5.

Savander M, Ropponen A, Avela K, et al. Genetic evidence of heterogeneity in intrahepatic cholestasis of pregnancy. Gut 2003;52:1025–9.

Heinonen S, Kirkinen P. Pregnancy outcome with intrahepatic cholestasis. Obstet Gynecol 1999;94:189–93.

Floreani A, Gervasi M. New Insights on Intrahepatic Cholestasis of Pregnancy. Clinics in Liver Disease. 2016;20(1):177-189.

Walker IA, Nelson-Piercy C, Williamson C. Role of bile acid measurement in pregnancy. Ann Clin Biochem 2002;39:105–13.

Kremer AE, Bolier R, Dixon PH, et al. Autotaxin activity has a high accuracy to diagnose intrahepatic cholestasis of pregnancy. J Hepatol 2015;62:897–904.

Williamson C, Geenes V. Intrahepatic Cholestasis of Pregnancy. Obstetrics & Gynecology. 2014;124(1):120-133.

Bacq Y, Sentilhes L, Reyes HB, et al. Efficacy of ursodeoxycholic acid in treating intrahepatic cholestasis of pregnancy: a meta-analysis. Gastroenterology 2012; 143:1492–501.

Grand’Maison S, Durand M, Mahone M. The effect of ursodeoxycholic acid treatment for intrahepatic cholestasis of pregnancy on maternal and fetal outcomes: a meta-analysis including non-randomized studies. J Obstet Gynaecol Can 2014; 36:632–41.

Kong X, Kong Y, Zhang F, Wang T, Yan J. Evaluating the effectiveness and safety of ursodeoxycholic acid in treatment of intrahepatic cholestasis of pregnancy. Medicine. 2016;95(40):e4949.

Erlinger S. Ursodeoxycholic acid in intrahepatic cholestasis of pregnancy: good, but can do better. Clin Res Hepatol Gastroenterol 2013;37:117–8.

Estiu` MC, Monte MJ, Rivas L, et al. Effects of ursodeoxycholic acid treatment on the altered progesterone and bile acid homeostasis in the mother-placentafoetus trio during cholestasis of pregnancy. Br J Clin Pharmacol 2014;79:316–29.

Gurung V, Stokes M, Middleton P, et al. Interventions for treating cholestasis in pregnancy [review]. Cochrane Database Syst Rev 2013;(6):CD000493.

Ovadia C, Seed P, Sklavounos A, Geenes V, Di Ilio 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;393(10174):899-909.

Brouwers L, Koster M, Page-Christiaens G, Kemperman H, Boon J, Evers I et al. Intrahepatic cholestasis of pregnancy: maternal and fetal outcomes associated with elevated bile acid levels. American Journal of Obstetrics and Gynecology. 2015;212(1):100.e1-100.e7.

Sheikh Abdul Kadir SH, Miragoli M, Abu-Hayyeh S, et al. Bile acid–induced arrhythmia is mediated by muscarinic M2 receptors in neonatal rat cardiomyocytes. PLoS One 2010; 5:e9689.

Williamson C, Gorelik J, Eaton BM, Lab M, de Swiet M, Korchev Y. The bile acid taurocholate impairs rat cardiomyocyte function: a proposed mechanism for intra-uterine fetal death in obstetric cholestasis. Clin Sci (Lond) 2001; 100:363–369.

Gorelik J, Harding SE, Shevchuk AI, et al. Taurocholate induces changes in rat cardiomyocyte contraction and calcium dynamics. Clin Sci (Lond) 2002; 103:191–200.

Binah O, Rubinstein I, Bomzon A, Better OS. Effects of bile acids on ventricular muscle contraction and electrophysiological properties: studies in rat papillary muscle and isolated ventricular myocytes. Naunyn Schmiedebergs Arch Pharmacol 1987; 335:160–165.

Mays JK. The active management of intrahepatic cholestasis of pregnancy. Curr Opin Obstet Gynecol 2010; 22:100–103.

Al Inizi S, Gupta R, Gale A. Fetal tachyarrhythmia with atrial flutter in obstetric cholestasis. Int J Gynaecol Obstet 2006; 93:53–54.

Shand AW, Dickinson JE, D’Orsogna L. Refractory fetal supraventricular tachycardia and obstetric cholestasis. Fetal Diagn Ther 2008; 24:277–281.

Strehlow SL, Pathak B, Goodwin TM, Perez BM, Ebrahimi M, Lee RH. The mechanical PR interval in fetuses of women with intrahepatic cholestasis of pregnancy. Am J Obstet Gynecol 2010; 203:455.e1–455.e5.

Fan X, Zhou Q, Zeng S, Zhou J, Peng Q, Zhang M et al. Impaired Fetal Myocardial Deformation in Intrahepatic Cholestasis of Pregnancy. Journal of Ultrasound in Medicine. 2014;33(7):1171-1177.

Puljic A, Kim E, Page J, et al. The risk of infant and fetal death by each additional week of expectant management in intrahepatic cholestasis of pregnancy by gestational age. Am J Obstet Gynecol 2015;212:667.e1–5.

Lo JO, Shaffer BL, Allen AJ, Little SE, Cheng YW, Caughey AB. Intrahepatic cholestasis of pregnancy and timing of delivery. J Matern Neonatal Med 2015;28: 2254–58.

How to Cite
Yanque-Robles O. Intrahepatic cholestasis of pregnancy. Rev Peru Investig Salud [Internet]. 28Jan.2020 [cited 25Sep.2020];4(1):37-2. Available from:
Artículos de revisión