Intrahepatic cholestasis of pregnancy

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Intrahepatic cholestasis of pregnancy (also called ICP) is a liver disorder that typically occurs during the second half of pregnancy. Cholestasis is a condition that impairs the release of a digestive fluid called bile, which is made and released by the liver. In people with cholestasis, bile builds up in the liver, impairing its function. Because the problems with bile release occur within the liver (intrahepatic), the condition is described as intrahepatic cholestasis.

Severe itchiness (pruritus) is typically one of the first symptoms of intrahepatic cholestasis of pregnancy. The itchiness usually begins on the palms of the hands and the soles of the feet before spreading to other parts of the body. Women with intrahepatic cholestasis of pregnancy have a buildup of bile acids in the blood. Bile acids are a component of bile and are produced when the liver processes cholesterol. Bile acid levels in the blood are normally low, but they can increase in people with liver disease.

Occasionally, women with intrahepatic cholestasis of pregnancy have yellowing of the skin and whites of the eyes (jaundice). Women with intrahepatic cholestasis of pregnancy typically do not continue to have signs and symptoms of the condition after having the baby, though they may have an increased risk of developing disorders of the gallbladder, liver, or heart later in life.

Intrahepatic cholestasis of pregnancy can cause problems for the baby. This condition is associated with an increased risk of premature delivery and breathing problems in the newborn (meconium aspiration). Some infants born to women with intrahepatic cholestasis of pregnancy experience a slow heart rate and a lack of oxygen during delivery (fetal distress). Women with higher levels of bile acids in their blood also have an increased risk of stillbirth.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Intrahepatic cholestasis of pregnancy is a complex disorder. It is believed to be caused by a combination of genetic, hormonal, and environmental factors. Risk factors for developing intrahepatic cholestasis of pregnancy include underlying liver disease and a form of diabetes called gestational diabetes that occurs during pregnancy. Being pregnant with more than one baby or having a history of intrahepatic cholestasis of pregnancy also increases the risk of developing this condition. Sometimes, more than one person in a family has this condition.

Variants in several different genes are believed to increase the risk of developing intrahepatic cholestasis of pregnancy. Many of these genes provide instructions for making proteins that help with the production (synthesis) or transportation of bile acids. In most cases, the variants that increase the risk of developing intrahepatic cholestasis of pregnancy are present in only one of the two copies of the gene,

The largest genetic contributor is the ABCB4 gene; variants in this gene have been found in up to 25 percent of women with intrahepatic cholestasis of pregnancy. The ABCB4 gene provides instructions for making a protein that helps move certain fats called phospholipids across cell membranes before releasing them into bile. Phospholipids attach (bind) to bile acids. Large amounts of bile acids can be toxic when they are not bound to phospholipids. Many of the variants in the ABCB4 gene that have been found in women with intrahepatic cholestasis of pregnancy cause one protein building block (amino acid) to be substituted for another. A few ABCB4 gene variants cause the cell to produce an abnormally short protein. Variants in other genes have been found to have a more limited contribution to the risk of developing intrahepatic cholestasis of pregnancy.

Even with these variants, enough protein is still available in most cases to move an adequate amount of phospholipids out of liver cells to bind to bile acids. The added stress on the liver during pregnancy, however, contributes to the buildup of bile acids. Toxic levels of bile acids can impair liver function, including the regulation of bile flow.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

An increased susceptibility to intrahepatic cholestasis of pregnancy typically has an autosomal dominant pattern of inheritance, which means one copy of the altered gene in each cell is sufficient to increase the risk of developing the disorder.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Intrahepatic cholestasis of pregnancy is the most common liver disease related to pregnancy. It is estimated to affect up to 2 percent of pregnancies, although the number of people affected varies by country and population. The condition is more common in South America and northern Europe. Historically, the highest incidence occurred in the Araucanian Indian population in Chile, although the incidence in this population has declined in recent years.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Increased serum bile acid concentration · Very frequent (99-80%)

An increase in the concentration of bile acid in the blood.

Pruritus · Very frequent (99-80%)

Pruritus is an itch or a sensation that makes a person want to scratch. This term refers to an abnormally increased disposition to experience pruritus.

Elevated circulating hepatic transaminase concentration · Frequent (79-30%)

Elevations of the levels of SGOT and SGPT in the serum. SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase) are transaminases primarily found in the liver and heart and are released into the bloodstream as the result of liver or heart damage. SGOT and SGPT are used clinically mainly as markers of liver damage.

Insomnia · Frequent (79-30%)

Persistent difficulty in starting or maintaining sleep, or waking up earlier than desired, despite having adequate opportunities and conditions for sleep.

Abnormality of the digestive system · Frequent (79-30%)

Abnormal circulating interleukin concentration · Occasional (29-5%)

The concentration of an interleukin (a class of cytokines) is outside the limits of normal.

Abnormal pineal melatonin secretion · Occasional (29-5%)

An anomaly in the amount or timing of melatonin secretion by the pineal gland. Note that melatonin is also synthesized by multiple tissues outside of the pineal gland.

Depression · Occasional (29-5%)

Frequently experiencing feelings of being down, miserable, and/or hopeless; struggling to recover from these moods; having a pessimistic outlook on the future; feeling a pervasive sense of shame; having a low self-worth; experiencing thoughts of suicide and engaging in suicidal behavior.

Other findings in the same source

From: Orphanet

Additional reported features include Elevated circulating alkaline phosphatase concentration (Occasional (29-5%)); Hyperbilirubinemia (Occasional (29-5%)); Meconium stained amniotic fluid (Occasional (29-5%)); Neonatal respiratory distress (Occasional (29-5%)); Palmar pruritus (Occasional (29-5%)); Preeclampsia (Occasional (29-5%)); Pruritus on foot (Occasional (29-5%)); Abdominal pain (Very rare (<4-1%)); Abnormality of the pancreas (Very rare (<4-1%)); Ascites (Very rare (<4-1%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Intrahepatic cholestasis of pregnancy is Hepatology, with a hepatologist / gastroenterologist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• What is known about the cause and extent of liver involvement?
• Which medicines, supplements or exposures should be reviewed?
• What follow-up is appropriate for the specific diagnosis and stage?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Intrahepatic cholestasis of pregnancy. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.