Treatment of Intrahepatic Cholestasis of Pregnancy
Ursodeoxycholic acid (UDCA) is the first-line treatment for intrahepatic cholestasis of pregnancy (ICP), with a recommended dosage of 10-15 mg/kg/day divided into 2-3 doses (typically 300 mg 2-3 times daily or 500 mg twice daily). 1
Diagnosis and Risk Stratification
ICP diagnosis is based on:
- Maternal pruritus
- Elevated serum bile acids ≥11 μmol/L
- Elevated liver enzymes
- Exclusion of other causes of liver dysfunction 1
Risk stratification is determined by total serum bile acid (TSBA) levels:
- Low risk: <40 μmol/L (minimal stillbirth risk)
- Moderate risk: 40-99 μmol/L (0.3% stillbirth risk)
- High risk: ≥100 μmol/L (3.4% stillbirth risk) 1
Treatment Algorithm
First-Line Treatment
- UDCA 10-15 mg/kg/day divided into 2-3 doses
- Typical regimens: 300 mg 2-3 times daily or 500 mg twice daily 1
- Low-dose UDCA (300-450 mg/day; 4-6 mg/kg/day) has shown efficacy in improving biochemical markers and clinical symptoms in almost 90% of ICP patients 2
- UDCA improves maternal pruritus, reduces total bile acid levels, and improves liver function tests 1
For Persistent Symptoms Despite UDCA
- Rifampicin (300-600 mg daily) may be considered
- Monitor for hepatotoxicity
- Anion exchange resins (cholestyramine 4-8 g/day) may be considered
- Monitor for vitamin K deficiency
- S-adenosyl-L-methionine may have additive effects with UDCA 1
Supportive Measures
- Mild soaps and lukewarm water for bathing
- Topical emollients
- Cool compresses
- Loose-fitting cotton clothing
- Low to mid-potency topical corticosteroids for symptomatic relief
- Antihistamines (e.g., diphenhydramine or hydroxyzine) may help with sleep 1
Monitoring and Delivery Timing
Laboratory Monitoring
- Repeat TSBA and liver function tests every 2 weeks until 32 weeks gestation, then weekly until delivery
- More intensive monitoring for patients with bile acids ≥40 μmol/L
- Monitor coagulation parameters, especially if using cholestyramine
- Correct vitamin K deficiency if present 1
Fetal Surveillance
- Begin antenatal fetal surveillance at diagnosis
- More intensive monitoring for patients with bile acids ≥40 μmol/L 1
Timing of Delivery (based on bile acid levels)
- ≥100 μmol/L: Deliver at 36 weeks
- 40-99 μmol/L: Deliver at 37-38 weeks
- <40 μmol/L: Deliver at 38-39 weeks 1
Postpartum Management
- Stop UDCA at delivery
- If symptoms persist, taper UDCA over 2-4 weeks post-delivery
- Bile acids and liver enzymes should normalize within 3 months
- If abnormalities persist beyond 6 weeks postpartum, investigate for underlying liver disease
- Follow-up after 2-3 years due to increased risk for hepatobiliary and immune-mediated diseases 1
Safety and Efficacy Considerations
UDCA is generally well-tolerated during pregnancy:
- Studies report minimal side effects, including mild diarrhea (4.7%) and skin reactions (0.5%) 3
- No complications attributable to UDCA treatment have been detected during fetal life, delivery, or early neonatal period 3
Important Caveats
Conflicting Evidence: While most studies support UDCA use, the PITCHES trial (2019) found that UDCA did not reduce adverse perinatal outcomes compared to placebo 4. However, current guidelines still recommend UDCA as first-line therapy based on its proven benefits for maternal symptoms and biochemical improvement 1.
Severe ICP Requires Urgent Management: Patients with severe ICP (total BA > 40 μmol/L) should be identified promptly as they have higher risk of adverse outcomes including preterm birth 5.
Multidisciplinary Approach: Severe cases benefit from management involving maternal-fetal medicine and hepatology 1.
Recurrence Risk: Patients have a 45-70% recurrence rate in subsequent pregnancies 1.
Early Treatment Benefits: Studies suggest that early diagnosis and treatment with UDCA may improve outcomes, with even low-dose UDCA (300-450 mg/day) showing efficacy in improving symptoms and biochemical markers 2, 5, 6.