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Genetics Home Reference: your guide to understanding genetic conditions
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Intrahepatic cholestasis of pregnancy

Reviewed June 2012

What is intrahepatic cholestasis of pregnancy?

Intrahepatic cholestasis of pregnancy is a liver disorder that occurs in pregnant women. Cholestasis is a condition that impairs the release of a digestive fluid called bile from liver cells. As a result, bile builds up in the liver, impairing liver function. Because the problems with bile release occur within the liver (intrahepatic), the condition is described as intrahepatic cholestasis. Intrahepatic cholestasis of pregnancy usually becomes apparent in the third trimester of pregnancy. Bile flow returns to normal after delivery of the baby, and the signs and symptoms of the condition disappear. However, they can return during later pregnancies.

This condition causes severe itchiness (pruritus) in the expectant mother. The itchiness usually begins on the palms of the hands and the soles of the feet and then spreads to other parts of the body. Occasionally, affected women have yellowing of the skin and whites of the eyes (jaundice). Some studies have shown that women with intrahepatic cholestasis of pregnancy are more likely to develop gallstones sometime in their life than women who do not have the condition.

Intrahepatic cholestasis of pregnancy can cause problems for the unborn baby. This condition is associated with an increased risk of premature delivery and stillbirth. Additionally, some infants born to mothers with intrahepatic cholestasis of pregnancy have a slow heart rate and a lack of oxygen during delivery (fetal distress).

How common is intrahepatic cholestasis of pregnancy?

Intrahepatic cholestasis of pregnancy is estimated to affect 1 percent of people of Northern European ancestry. The condition is more common in certain populations, such as people of Araucanian Indian ancestry in Chile or people of Scandinavian ancestry. This condition is found less frequently in other populations.

What genes are related to intrahepatic cholestasis of pregnancy?

Genetic changes in the ABCB11 or the ABCB4 gene can increase a woman's likelihood of developing intrahepatic cholestasis of pregnancy.

The ABCB11 gene provides instructions for making a protein called the bile salt export pump (BSEP). This protein is found in the liver, and its main role is to move bile salts (a component of bile) out of liver cells, which is important for the normal release of bile. Changes in the ABCB11 gene associated with intrahepatic cholestasis of pregnancy reduce the amount or function of the BSEP protein, although enough function remains for sufficient bile secretion under most circumstances. Studies show that the hormones estrogen and progesterone (and products formed during their breakdown), which are elevated during pregnancy, further reduce the function of BSEP, resulting in impaired bile secretion and the features of intrahepatic cholestasis of pregnancy.

The ABCB4 gene provides instructions for making a protein that helps move certain fats called phospholipids across cell membranes and release them into bile. Phospholipids attach (bind) to bile acids (another component of bile). Large amounts of bile acids can be toxic when they are not bound to phospholipids. A mutation in one copy of the ABCB4 gene mildly reduces the amount of the ABCB4 protein. Under most circumstances, though, enough protein is available to move an adequate amount of phospholipids out of liver cells to bind to bile acids. Although the mechanism is unclear, the function of the remaining ABCB4 protein appears to be impaired during pregnancy, which may further reduce the movement of phospholipids into bile. The lack of phospholipids available to bind to bile acids leads to a buildup of toxic bile acids that can impair liver function, including the regulation of bile flow.

Most women with intrahepatic cholestasis of pregnancy do not have a genetic change in the ABCB11 or ABCB4 gene. Other genetic and environmental factors likely play a role in increasing susceptibility to this condition.

Related Gene(s)

Changes in these genes are associated with intrahepatic cholestasis of pregnancy.

  • ABCB11
  • ABCB4

How do people inherit intrahepatic cholestasis of pregnancy?

Susceptibility to intrahepatic cholestasis of pregnancy is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to increase the risk of developing the disorder. Some women with an altered gene do not develop intrahepatic cholestasis of pregnancy. Many other factors likely contribute to the risk of developing this complex disorder.

Where can I find information about diagnosis or management of intrahepatic cholestasis of pregnancy?

These resources address the diagnosis or management of intrahepatic cholestasis of pregnancy and may include treatment providers.

  • Gene Review: ATP8B1 Deficiency (http://www.ncbi.nlm.nih.gov/books/NBK1297)
  • Genetic Testing Registry: Cholestasis of pregnancy (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0268318)

You might also find information on the diagnosis or management of intrahepatic cholestasis of pregnancy in Educational resources (http://ghr.nlm.nih.gov/condition/intrahepatic-cholestasis-of-pregnancy/show/Educational+resources) and Patient support (http://ghr.nlm.nih.gov/condition/intrahepatic-cholestasis-of-pregnancy/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about intrahepatic cholestasis of pregnancy?

You may find the following resources about intrahepatic cholestasis of pregnancy helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for intrahepatic cholestasis of pregnancy?

  • obstetric cholestasis
  • pregnancy-related cholestasis
  • recurrent intrahepatic cholestasis of pregnancy

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about intrahepatic cholestasis of pregnancy?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding intrahepatic cholestasis of pregnancy?

acids ; autosomal ; autosomal dominant ; bile ; breakdown ; cell ; digestive ; gene ; inherited ; jaundice ; mutation ; oxygen ; phospholipids ; progesterone ; protein ; secretion ; susceptibility ; toxic

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

References

  • Bacq Y, Gendrot C, Perrotin F, Lefrou L, Chrétien S, Vie-Buret V, Brechot MC, Andres CR. ABCB4 gene mutations and single-nucleotide polymorphisms in women with intrahepatic cholestasis of pregnancy. J Med Genet. 2009 Oct;46(10):711-5. doi: 10.1136/jmg.2009.067397. Epub 2009 Jul 6. (http://www.ncbi.nlm.nih.gov/pubmed/19584064?dopt=Abstract)
  • Dixon PH, van Mil SW, Chambers J, Strautnieks S, Thompson RJ, Lammert F, Kubitz R, Keitel V, Glantz A, Mattsson LA, Marschall HU, Molokhia M, Moore GE, Linton KJ, Williamson C. Contribution of variant alleles of ABCB11 to susceptibility to intrahepatic cholestasis of pregnancy. Gut. 2009 Apr;58(4):537-44. doi: 10.1136/gut.2008.159541. Epub 2008 Nov 5. (http://www.ncbi.nlm.nih.gov/pubmed/18987030?dopt=Abstract)
  • Dixon PH, Weerasekera N, Linton KJ, Donaldson O, Chambers J, Egginton E, Weaver J, Nelson-Piercy C, de Swiet M, Warnes G, Elias E, Higgins CF, Johnston DG, McCarthy MI, Williamson C. Heterozygous MDR3 missense mutation associated with intrahepatic cholestasis of pregnancy: evidence for a defect in protein trafficking. Hum Mol Genet. 2000 May 1;9(8):1209-17. (http://www.ncbi.nlm.nih.gov/pubmed/10767346?dopt=Abstract)
  • Meier Y, Zodan T, Lang C, Zimmermann R, Kullak-Ublick GA, Meier PJ, Stieger B, Pauli-Magnus C. Increased susceptibility for intrahepatic cholestasis of pregnancy and contraceptive-induced cholestasis in carriers of the 1331T>C polymorphism in the bile salt export pump. World J Gastroenterol. 2008 Jan 7;14(1):38-45. (http://www.ncbi.nlm.nih.gov/pubmed/18176959?dopt=Abstract)
  • Pauli-Magnus C, Meier PJ, Stieger B. Genetic determinants of drug-induced cholestasis and intrahepatic cholestasis of pregnancy. Semin Liver Dis. 2010 May;30(2):147-59. doi: 10.1055/s-0030-1253224. Epub 2010 Apr 26. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20422497?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: June 2012
Published: September 15, 2014