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

Management of Intrahepatic Cholestasis of Pregnancy

Ursodeoxycholic acid (UDCA) at 10-15 mg/kg/day should be initiated immediately upon diagnosis of ICP, with delivery timing determined by serum bile acid levels: at 36 weeks for levels ≥100 μmol/L, between 36-39 weeks for levels <100 μmol/L, and at term for levels <40 μmol/L. 1, 2

Diagnosis and Initial Assessment

Diagnostic Criteria:

• Diagnose ICP based on pruritus (typically in second or third trimester) plus serum bile acids >10 μmol/L 1, 2
• Measure serum bile acids, ALT, AST, and bilirubin at presentation 1
• If bile acids are initially normal but pruritus persists, repeat testing as bile acid elevation may lag behind symptoms 1, 2
• Exclude other causes including viral hepatitis, biliary obstruction, and chronic liver disease 1

Risk Stratification by Bile Acid Levels:

• <40 μmol/L: Lower risk 1, 2
• 40-100 μmol/L: Moderate risk requiring weekly monitoring 1

• 100 μmol/L: High risk for stillbirth, particularly after 35 weeks 1, 2

Pharmacological Treatment

First-Line Therapy:

• Start UDCA at 10-15 mg/kg/day in divided doses immediately upon diagnosis 1, 2
• UDCA reduces spontaneous preterm birth risk and may protect against stillbirth in patients with bile acids >40 μmol/L 1
• UDCA improves maternal pruritus, though the effect may be modest 1
• If inadequate response after several days, increase dose up to 21-25 mg/kg/day 1, 2

Second-Line and Adjunctive Therapies:

• For refractory pruritus despite UDCA, consider adding rifampicin, cholestyramine, guar gum, or activated charcoal 1
• S-adenosyl-methionine is less effective than UDCA alone but may provide additive benefit when combined 1, 3
• Separate UDCA and cholestyramine administration by at least 4 hours to prevent binding 1
• Monitor for vitamin K deficiency with cholestyramine use; provide replacement if needed 1

Monitoring Protocol

Maternal Monitoring:

• Measure serum bile acids at least weekly starting at 32 weeks' gestation to identify rising levels >40 μmol/L 1
• Continue monitoring bile acids after starting UDCA, recognizing that UDCA itself is measured by enzymatic bile acid assays 1
• Monitor liver function tests (ALT, AST, bilirubin) regularly 1

Fetal Surveillance:

• Begin antepartum fetal surveillance at a gestational age when delivery would be performed in response to abnormal testing 2
• Intensify monitoring in patients with bile acids >40 μmol/L 1

Delivery Timing

Evidence-Based Delivery Guidelines:

• Bile acids ≥100 μmol/L: Deliver at 36 0/7 weeks or at diagnosis if after 36 weeks, as stillbirth risk increases markedly after 35 weeks 1, 2
• Bile acids 40-99 μmol/L: Deliver between 36 0/7 and 39 0/7 weeks 1, 2
• Bile acids <40 μmol/L: Consider delivery at term 2
• Administer antenatal corticosteroids for fetal lung maturity if delivery planned before 37 weeks 2

Postpartum Management

Immediate Postpartum:

• Discontinue UDCA at delivery 2
• If symptoms persist, consider gradual UDCA reduction over 2-4 weeks postpartum 2

Follow-Up:

• Repeat biochemical testing if symptoms or abnormal liver tests persist 4-6 weeks after delivery 2
• Persistent abnormalities warrant investigation for underlying chronic liver disease including primary biliary cholangitis, primary sclerosing cholangitis, ABCB4 deficiency, or chronic hepatitis C 1, 2
• Consider genetic screening if family history of hepatobiliary disease, early onset, or severe disease 1

Multidisciplinary Care

• Manage high-risk ICP cases with a multidisciplinary team including a physician, obstetrician, and midwife with expertise in liver disease in pregnancy 1
• Refer to specialized centers if local expertise unavailable 1

Critical Pitfalls to Avoid

Common Errors:

• Do not delay UDCA initiation while awaiting repeat bile acid levels in symptomatic patients 1
• Do not rely solely on ALT/AST; bile acids are the most sensitive indicator and best predictor of fetal risk 1
• Do not continue pregnancy beyond 36 weeks in patients with bile acids >100 μmol/L due to exponentially increasing stillbirth risk 1
• Do not use dexamethasone as primary ICP treatment; it is ineffective for pruritus and liver biochemistry 1