Intrahepatic cholestasis of pregnancy !

A liver problem of late pregnancy causing intense itching of palms and soles from raised bile acids. It goes away after birth but can harm the baby.

Updated 2026-11-01

Structures involved

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Why it happens

What it is

A pregnancy-specific liver disorder in which bile flow is reduced and bile acids accumulate in the mother’s blood. It typically appears in the late second or third trimester with generalised itching without a primary rash, and resolves after delivery. Its importance lies in the fetal risks.

Who gets it

The most common liver disease specific to pregnancy. Frequency varies widely by ethnicity and region: in many countries it affects under 1% of pregnancies, while Chile and Bolivia have historically reported some of the highest rates in the world, especially in Indigenous women. It recurs in a large share of later pregnancies.

Causes

High levels of oestrogen and progesterone metabolites in late pregnancy, which impair bile transport
Genetic predisposition: variants in hepatocyte bile transporter genes (ABCB4 is the most important; also ABCB11, ATP8B1)
Environmental factors (seasonal variation, low selenium and vitamin D have been suggested)

Risk factors

Previous pregnancy with cholestasis
Family history (mother or sister)
Multiple pregnancy
In vitro fertilisation
Advanced maternal age
Chronic hepatitis C or other pre-existing liver disease
Ethnic background (Chilean and Andean Indigenous ancestry)

Pathophysiology

Pregnancy hormones and their metabolites, in women with genetically less efficient canalicular transporters, reduce the secretion of bile acids from hepatocytes into the bile. Bile acids accumulate in maternal blood, causing itching, and cross the placenta. In the fetus, high bile acids can cause cardiac arrhythmias, constriction of placental vessels and stimulation of the colon and myometrium, which explains meconium-stained fluid, preterm labour and sudden intrauterine death. Fat malabsorption can lower vitamin K.

Classification

Mild: total serum bile acids raised but below 40 µmol/L
Severe: total serum bile acids 40 µmol/L or more
Very high risk: total serum bile acids 100 µmol/L or more (stillbirth risk rises sharply)

Symptoms and signs

Itching, often intense and worse at night, typically starting on the palms and soles and then spreading
No primary rash; only scratch marks (excoriations)
Insomnia and fatigue from itching
Mild jaundice in a minority, usually after the itching
Dark urine or pale stools occasionally

Diagnosis

Clinical: Pruritus without a rash in the second half of pregnancy, with raised serum bile acids and no other explanation, and resolution after delivery.
Tests: Total serum bile acids (key test; ideally non-fasting and repeated); liver transaminases are often raised. Rule out other causes: viral hepatitis serology, autoimmune liver markers. Prothrombin time if there is steatorrhoea or severe disease. Repeat liver tests after delivery to confirm normalisation.
Imaging: Liver and biliary ultrasound to exclude gallstones or biliary obstruction; it is normal in cholestasis of pregnancy.

Differential diagnosis

Gallstones with biliary obstruction
Viral hepatitis
Preeclampsia and HELLP syndrome
Acute fatty liver of pregnancy
Primary biliary cholangitis or other chronic cholestatic disease
Pregnancy dermatoses (polymorphic eruption, pemphigoid gestationis) and atopic eruption

Goal of treatment

Relieve maternal itching, lower bile acid levels and reduce fetal risk through surveillance and well-timed delivery.

Treatment

Medical: Ursodeoxycholic acid is the usual first-line drug: it improves itching and liver tests. Topical emollients and some antihistamines are used for symptom relief.
Follow-up: Serial bile acids and liver tests, fetal surveillance and teaching the mother to report reduced fetal movements.
Procedure: Planned delivery timed by bile acid level: usually around 38–39 weeks in mild disease, earlier (around 35–36 weeks) in very severe disease, with antenatal corticosteroids if preterm.
Medical: Vitamin K supplementation if prothrombin time is prolonged or there is fat malabsorption.
Conservative: Cool clothing, lukewarm baths and short nails to limit skin damage from scratching.

Complications

Stillbirth (risk rises with bile acids at or above 100 µmol/L)
Spontaneous preterm birth and iatrogenic preterm delivery
Meconium-stained amniotic fluid and fetal distress
Neonatal respiratory distress
Associated maternal gestational diabetes and preeclampsia
Recurrence in later pregnancies and higher lifetime risk of gallstones and hepatobiliary disease

Prognosis

For the mother it is benign: itching usually stops within days of delivery and liver tests normalise within weeks. Fetal outcome is good with surveillance and timely delivery. Recurrence in a later pregnancy is common, and symptoms may appear with combined hormonal contraceptives.

Prevention

Cannot be prevented
Women with a previous episode should have early bile acid testing if itching appears in a later pregnancy

Test yourself

Think of the answer, then tap the question to see it.

What is the classic presentation of intrahepatic cholestasis of pregnancy?

Intense itching of the palms and soles, worse at night, in the third trimester, without a primary rash.

What is the key laboratory test?

Total serum bile acids, which are raised; transaminases may also be raised.

What is the most feared complication?

Sudden intrauterine fetal death, especially when bile acids are 100 µmol/L or more.

What is the first-line drug for itching?

Ursodeoxycholic acid.

Which South American country has historically reported one of the highest rates?

Chile (also Bolivia), particularly in women of Indigenous ancestry.

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Educational information, not medical advice. For any symptom, see a health professional.

Sources: Intrahepatic cholestasis of pregnancy (MedlinePlus Genetics (U.S. National Library of Medicine), 2024); Cholestasis of Pregnancy (Cleveland Clinic, 2024).

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Representative model, for educational purposes only.

Liver highlighted on the Durgical 3D model