Intrahepatic cholestasis of pregnancy

Definition

• Intrahepatic cholestasis of pregnancy is the commonest pregnancy-specific liver disease; it presents with new-onset pruritus and raised serum bile acids in the second or third trimester, usually after 30 weeks.
• The clinical signs resolve rapidly after birth.

Occurrence & epidemiology

Epidemiology

• Frequency varies greatly by ethnicity and region: in Europe, North America and Australia about 1–2% of pregnant women are affected, among Andean natives up to 25%; it is highest in Bolivia and Chile.
• It recurs in 45–90% of subsequent pregnancies, often in a more severe form.

Aetiopathogenesis

Aetiology and risk factors

• The aetiology is multifactorial: oestrogen and progesterone levels, which rise until the third trimester, exaggerate physiological bile stasis, and genetic factors such as mutations of hepatobiliary transport proteins (MDR3, BSEP) contribute.

Clinical features

Clinical features and complications

• The leading symptom is intense itching, mostly of the palms and soles and worse at night, but not confined to these areas; pain and systemic symptoms are absent, and mild jaundice follows in about 10–15%.
• Fetal and neonatal risks include stillbirth, preterm birth, asphyxia, respiratory distress syndrome and meconium-stained fluid; the maternal risk of pre-eclampsia is increased.

Diagnosis

• The most important and most sensitive laboratory marker is total serum bile acids; the cut-off is a concentration above 10 µmol/L, and bile acids may be the first or only abnormal laboratory finding.
• From 40 µmol/L the risk of fetal complications rises; in a large analysis the stillbirth rate at levels of 100 µmol/L or more was 3.44%.
• Transaminases are often raised as well.

Keep learning in the app

Further reading (selection)

1. StatPearls: Pregnancy Intrahepatic Cholestasis (NCBI Bookshelf)
2. J Clin Med 2020: Intrahepatic Cholestasis in Pregnancy – Review of the Literature (PMC, open access)
3. MSD Manual Professional Edition: Hepatic Disorders in Pregnancy

Cross-references