What is the appropriate workup and treatment for a pregnant patient suspected of having intrahepatic cholestasis of pregnancy (ICP)?

Workup for Intrahepatic Cholestasis of Pregnancy

Immediate Laboratory Testing

Order random (non-fasting) total serum bile acids and liver transaminases (ALT/AST) immediately in any pregnant woman presenting with pruritus in the second or third trimester. 1, 2

• Total serum bile acids >10 μmol/L is diagnostic for ICP when combined with pruritus and exclusion of other causes 1, 2
• Use enzymatic assay for bile acid testing (results in 4 hours to 4 days) rather than mass spectrometry (4-14 days delay) 1, 2
• Random samples are acceptable and more practical than fasting samples—the difference is clinically insignificant 1, 2
• Elevated transaminases (typically <500 U/L) support the diagnosis but are not required 1, 3

Clinical Assessment

Focus on specific pruritus characteristics that distinguish ICP from other conditions:

• Pruritus affecting palms and soles, worsening at night, without a primary rash (only excoriations from scratching) 2, 3
• Onset typically in late second or third trimester 1, 3
• Prior pregnancy history—up to 90% recurrence risk in subsequent pregnancies 3
• Family history of ICP suggests genetic susceptibility 1, 3
• Pre-existing hepatobiliary disease (hepatitis C, cirrhosis, gallstones) increases risk 1, 3

Exclude Alternative Diagnoses

Immediately rule out life-threatening conditions before confirming ICP:

• Pre-eclampsia/HELLP syndrome: Check complete blood count (platelets), LDH, and blood pressure 3
• Acute fatty liver of pregnancy (AFLP): Check coagulation studies and glucose 3
• Hepatobiliary ultrasound to exclude gallstones/biliary obstruction 3
• Consider thyroid function tests and renal function if pruritus without elevated bile acids 3

Critical pitfall: Jaundice is uncommon in ICP (only 10-15% of cases, bilirubin typically <5 mg/dL)—prominent jaundice should prompt urgent evaluation for HELLP or AFLP 3

Repeat Testing Strategy

If initial bile acids are normal but pruritus persists without alternative explanation:

• Repeat bile acid and transaminase measurements every 1-2 weeks until symptoms resolve or diagnosis is confirmed 2, 4
• Pruritus can precede bile acid elevation by several weeks 2, 4
• Bile acid levels can increase rapidly during pregnancy, particularly near term 2

Never diagnose ICP or make delivery decisions based on pruritus alone without laboratory confirmation of elevated bile acids 2, 4

Management Without Laboratory Confirmation

Do not initiate the following without confirmed elevated bile acids:

• Antenatal fetal surveillance 2, 4
• Delivery before 37 weeks 2, 4
• The evidence does not support increased fetal risk in patients with pruritus but persistently normal bile acids 2, 4

Consider empiric ursodeoxycholic acid (UDCA) for severe pruritus only after initial testing is complete and while awaiting repeat results, understanding this may complicate subsequent diagnosis 4

Early-Onset or Atypical Cases

For ICP presenting before the second trimester or with marked hyperbilirubinemia:

• Consider genetic evaluation for bile acid metabolism disorders (ABCB11, ABCB4, ATP8B1 mutations) 3, 5
• Refer to hepatology for co-management 5
• These cases may represent underlying hepatobiliary disease rather than typical ICP 1, 5

Postpartum Follow-Up

Repeat biochemical testing 4-6 weeks postpartum if symptoms or abnormal laboratory values persist:

• Refer to hepatology if results remain abnormal 2, 3
• Persistent abnormalities suggest underlying hepatobiliary disease that was unmasked by pregnancy 2, 3
• Women with ICP history have significantly elevated risk for later developing chronic hepatitis, liver fibrosis/cirrhosis, and cholangitis 3