What is the management of intrahepatic cholestasis of pregnancy (ICP)?

Management of Intrahepatic Cholestasis of Pregnancy (ICP)

Ursodeoxycholic acid (UDCA) should be used as the first-line treatment for intrahepatic cholestasis of pregnancy at a dose of 10-15 mg/kg/day to improve maternal symptoms and potentially reduce adverse perinatal outcomes. 1

Diagnosis

• ICP is diagnosed based on pruritus (typically in the second or third trimester) with total serum bile acid levels >10 μmol/L 1
• Laboratory testing should include serum bile acids and liver function tests (ALT, AST, bilirubin) 1
• If initial bile acid levels are normal but pruritus persists without other explanation, testing should be repeated as bile acid elevation may lag behind symptom onset 1
• Liver biopsy is generally not warranted for diagnosis 1

Pharmacological Management

First-line Treatment:

• UDCA at 10-15 mg/kg/day divided into 2-3 doses (typical regimens: 300 mg twice or three times daily, or 500 mg twice daily) 1
• Clinical improvement in pruritus usually occurs within 1-2 weeks, while biochemical improvement typically takes 3-4 weeks 1
• If pruritus is not relieved, the dose can be titrated up to a maximum of 21-25 mg/kg/day 1

Alternative/Additional Treatments for Refractory Cases:

• S-adenosyl-methionine may improve pruritus but is less effective than UDCA; can be used in combination with UDCA for additive effect 1, 2
• Rifampicin can be combined with UDCA for refractory cases 1
• Cholestyramine binds bile acids in the gut but has limited efficacy and significant gastrointestinal side effects 1
• Antihistamines (diphenhydramine, hydroxyzine) may provide limited symptomatic relief 1
• Topical treatments (menthol creams, calamine lotion) have limited benefit as pruritus is typically widespread 1

Monitoring

• Follow-up laboratory testing helps guide delivery timing, especially in severe cases, but serial weekly testing is not routinely recommended 1
• Bile acid levels correlate with risk of intrauterine fetal demise, with highest risk when levels exceed 100 μmol/L 1, 3
• Antepartum fetal surveillance should begin at a gestational age when delivery would be performed in response to abnormal testing 1

Delivery Timing

• For patients with total bile acid levels ≥100 μmol/L: delivery at 36 0/7 weeks or at diagnosis if after 36 weeks 1
• For patients with total bile acid levels <100 μmol/L: delivery between 36 0/7 and 39 0/7 weeks 1
• For patients with total bile acid levels <40 μmol/L: consider delivery at term 1
• Administer antenatal corticosteroids for fetal lung maturity if delivery occurs before 37 weeks 1

Post-Delivery Management

• UDCA treatment should be discontinued at delivery 1
• If symptoms persist, consider gradual reduction of UDCA 2-4 weeks postpartum 1
• If symptoms or abnormal liver tests persist for 4-6 weeks after delivery, repeat biochemical testing 1
• Persistent abnormalities after delivery should prompt investigation for underlying chronic liver diseases (PBC, PSC, ABCB4 deficiency, chronic hepatitis C) 1

Special Considerations

• ICP is associated with increased rates of preterm birth, meconium-stained amniotic fluid, fetal distress, and stillbirth 1, 3, 4
• The mechanism of stillbirth is thought to be a sudden event rather than a chronic placental process, which may limit the efficacy of traditional antepartum testing 1
• Women with ICP may have an increased risk of preeclampsia 1
• ICP has a high recurrence rate in subsequent pregnancies 3, 4

By following this management approach, clinicians can optimize maternal symptom relief and potentially reduce adverse perinatal outcomes in women with intrahepatic cholestasis of pregnancy.