Can I initiate ursodiol (ursodeoxycholic acid) therapy in a pregnant patient with a history of cholestasis of pregnancy, currently at 36 weeks gestation, who is experiencing severe pruritus despite a previously negative bile acid test?

Management of Suspected Intrahepatic Cholestasis of Pregnancy with Pruritus

Ursodeoxycholic acid should be initiated for this patient with history of cholestasis of pregnancy who is experiencing severe pruritus at 36 weeks, even with a previously negative bile acid test, as it is the recommended first-line treatment for maternal symptoms and may protect against adverse perinatal outcomes. 1

Diagnostic Considerations

When evaluating a patient with history of cholestasis in pregnancy who presents with pruritus:

1. Repeat bile acid testing is essential:

   • Total serum bile acids should be checked at least weekly after 32 weeks as they may continue to rise with advancing gestation 1
   • A negative bile acid test does not rule out intrahepatic cholestasis of pregnancy (ICP) if clinical symptoms are present, especially with prior history

2. Additional testing:

   • Check liver function tests (ALT/AST) along with bile acids
   • Rule out other causes of pruritus without rash (thyroid disorders, renal failure, etc.)

Treatment Algorithm

For this patient at 36 weeks with pruritus and history of ICP:

1. Initiate ursodeoxycholic acid (UDCA) immediately:

   • Recommended dosage: 10-15 mg/kg/day in divided doses 2
   • Typical starting dose is 500 mg twice daily, which can be adjusted based on response 1
   • UDCA is the first-line agent for treatment of maternal symptoms of ICP (Grade 1A recommendation) 1

2. Continue monitoring:

   • Repeat bile acid testing and liver function tests weekly until delivery 1
   • Monitor fetal status with appropriate surveillance

3. Delivery planning:

   • If bile acids remain normal: Consider delivery between 37-39 weeks 2
   • If bile acids become elevated:
     • ≥100 μmol/L: Offer delivery at 36 weeks (high risk) 1
     • 40-99 μmol/L: Consider delivery between 36-39 weeks (moderate risk) 2
     • <40 μmol/L: Consider delivery between 37-39 weeks (lower risk) 2

Evidence for UDCA Treatment

UDCA has multiple beneficial mechanisms of action in ICP:

• Increases secretory capacity of hepatocytes
• Enhances bile formation
• Protects hepatocytes and cholangiocytes from bile acid-mediated damage 1

Clinical benefits include:

• Reduction in maternal pruritus (typically within 3 days of treatment initiation) 3
• Improvement in maternal biochemical parameters 4
• Protection against spontaneous preterm birth in singleton pregnancies 1
• Possible protection against stillbirth 1, 5

Important Considerations

• UDCA is well-tolerated during pregnancy with minimal side effects (mild diarrhea in 4.7% of patients, skin reactions in 0.5%) 4
• Treatment should be stopped at delivery or gradually reduced 2-4 weeks post-delivery if symptoms persist 1
• Ensure bile acids and liver enzymes return to normal within 3 months of delivery 1

Potential Pitfalls

1. Waiting for positive bile acid test before treatment:

   • Delaying treatment while awaiting test results may prolong maternal discomfort and potentially increase fetal risk
   • With prior history and typical symptoms, treatment can be initiated while awaiting results

2. Inadequate monitoring:

   • Bile acids can rise rapidly in late pregnancy, requiring weekly testing
   • Delivery timing should be adjusted based on most recent bile acid levels

3. Drug interactions:

   • Bile acid sequestering agents (cholestyramine, colestipol) and aluminum-based antacids may interfere with UDCA absorption 6
   • Estrogens and lipid-lowering drugs may counteract UDCA effectiveness 6

By initiating UDCA now while awaiting repeat bile acid testing, you can provide symptomatic relief for the patient and potentially reduce the risk of adverse perinatal outcomes.