What is the recommended treatment for cholestasis (intrahepatic cholestasis of pregnancy) in pregnant women?

Management of Intrahepatic Cholestasis of Pregnancy (ICP)

Ursodeoxycholic acid (UDCA) should be used as first-line treatment for intrahepatic cholestasis of pregnancy to reduce maternal symptoms and potentially improve perinatal outcomes, with timing of delivery based on bile acid levels. 1

Diagnosis and Risk Stratification

• Diagnosis based on:

  • Maternal pruritus (typically worse at night and on palms/soles)
  • Elevated serum bile acids ≥11 μmol/L
  • Elevated liver enzymes (ALT/AST)
  • Exclusion of other causes of liver dysfunction

• Risk stratification by total serum bile acid (TSBA) levels:

  Bile Acid Level	Risk Category	Stillbirth Risk
  <40 μmol/L	Low	Minimal
  40-99 μmol/L	Moderate	0.3%
  ≥100 μmol/L	High	3.4%

Pharmacological Management

First-Line Treatment

• Ursodeoxycholic acid (UDCA):

  • Dosage: 10-15 mg/kg/day divided into 2-3 doses 1, 2
  • Typical regimens: 300 mg 2-3 times daily or 500 mg twice daily 1
  • Continue from diagnosis until delivery

• UDCA benefits:

  • Significantly improves maternal pruritus 1
  • Reduces total bile acid levels and improves liver function tests 1, 3
  • May reduce risk of spontaneous preterm birth 1
  • May be protective against stillbirth in cases with bile acids >40 μmol/L 1

Second-Line/Adjunctive Treatments

For persistent symptoms despite UDCA:

• Rifampicin (300-600 mg daily)

  • Monitor for hepatotoxicity (occurs in ~5% of patients) 1

• Anion exchange resins (cholestyramine 4-8 g/day)

  • Administer at least 4 hours apart from UDCA 1
  • Monitor for vitamin K deficiency

• S-adenosyl-L-methionine

  • May have additive effects with UDCA 4
  • Less effective than UDCA as monotherapy

Monitoring and Surveillance

• After diagnosis:

  • Repeat TSBA & liver function tests every 2 weeks until 32 weeks gestation
  • Then weekly until delivery 1

• Fetal surveillance:

  • Begin at diagnosis
  • More intensive monitoring for patients with bile acids ≥40 μmol/L

Delivery Planning

Timing of delivery based on bile acid levels:

• TSBA ≥100 μmol/L: Recommend delivery at 35-36 weeks' gestation 1
• TSBA 40-99 μmol/L: Consider delivery at 37-38 weeks' gestation
• TSBA <40 μmol/L: Consider delivery at 38-39 weeks' gestation

Postpartum Management

• Stop UDCA at delivery
• If symptoms persist, taper UDCA over 2-4 weeks post-delivery 1, 2
• Ensure TSBA, ALT/AST and bilirubin return to normal within 3 months 1
• If abnormalities persist beyond 6 weeks, investigate for underlying liver disease 2
• Consider genetic screening if family history of hepatobiliary disease, early onset or severe disease 1

Common Pitfalls to Avoid

1. Inadequate monitoring: Failure to monitor bile acid levels weekly after 32 weeks can miss worsening cholestasis
2. Delayed delivery: Not adjusting delivery timing based on bile acid levels increases stillbirth risk
3. Insufficient UDCA dosing: Using doses <10 mg/kg/day may be less effective
4. Overlooking vitamin K deficiency: Especially important when using cholestyramine
5. Failure to counsel about recurrence: ICP has 45-70% recurrence rate in subsequent pregnancies 2
6. Inadequate postpartum follow-up: Missing persistent abnormalities that could indicate underlying liver disease

Special Considerations

• About 10-15% of patients may not respond to UDCA treatment 3
• Women with ICP have increased risk of preeclampsia (aOR 2.62) 1
• Consider multidisciplinary management involving maternal-fetal medicine and hepatology for severe cases

While a large randomized trial questioned UDCA's benefit for improving perinatal outcomes 5, current guidelines still recommend its use due to its proven efficacy in relieving maternal symptoms and potential benefits in reducing adverse pregnancy outcomes, particularly in women with higher bile acid levels 1.