How is cholestasis (intrahepatic cholestasis of pregnancy) managed in pregnant women?

Management of Intrahepatic Cholestasis of Pregnancy

Intrahepatic cholestasis of pregnancy (ICP) should be diagnosed based on pruritus (typically affecting palms and soles) combined with serum bile acids >10 μmol/L, treated with ursodeoxycholic acid 10-15 mg/kg/day, and managed with bile acid-guided delivery timing: at 36 weeks for levels ≥100 μmol/L, between 36-39 weeks for levels <100 μmol/L, and at 39 weeks for levels <40 μmol/L. 1, 2

Diagnostic Approach

Initial Testing

• Measure serum bile acids and liver transaminases (ALT/AST) immediately in any pregnant woman presenting with pruritus in the second or third trimester, particularly if affecting palms and soles and worsening at night 1, 2
• Random (non-fasting) bile acid levels are acceptable and more convenient than fasting samples, as the clinical difference is insignificant 2
• Enzymatic bile acid assays are preferred when rapid results are needed (4 hours to 4 days) rather than mass spectrometry (4-14 days) 2

Diagnostic Criteria

• Bile acids >10 μmol/L are diagnostic when combined with pruritus 1, 2
• Transaminases are typically elevated (<500 U/L) but not required for diagnosis 2
• Bilirubin is typically <5 mg/dL, with jaundice occurring in only 10-15% of cases 2

Critical Diagnostic Pitfall

• If initial testing is normal but pruritus persists, repeat bile acids and transaminases as pruritus can precede bile acid elevation by several weeks 2, 3
• Never diagnose ICP or deliver preterm based on clinical suspicion alone without laboratory confirmation of elevated bile acids 2, 3
• Do not start ursodeoxycholic acid before obtaining initial laboratory confirmation, as this may prevent detection of elevated bile acids and make definitive diagnosis impossible 3

Differential Diagnosis to Exclude

• Immediately exclude pre-eclampsia/HELLP syndrome and acute fatty liver of pregnancy (AFLP) in any patient with elevated liver enzymes, as these carry significant maternal and fetal mortality risks and require immediate delivery 2
• HELLP syndrome presents with hemolysis, elevated liver enzymes, low platelets, and elevated LDH 2
• AFLP presents with elevated liver enzymes, bilirubin, and coagulopathy in the third trimester 2
• Check hepatobiliary ultrasound to exclude gallstones/biliary obstruction 2

Treatment

Pharmacologic Management

• Initiate ursodeoxycholic acid (UDCA) at 10-15 mg/kg/day in divided doses as first-line therapy for all confirmed ICP cases 1, 2
• UDCA improves maternal pruritus, reduces bile acid levels, and decreases adverse outcomes including preterm birth and stillbirth 1, 2
• UDCA should be continued throughout pregnancy and is safe during breastfeeding 1

Additional Therapies for Refractory Pruritus

• If pruritus remains severe despite UDCA, consider rifampicin, cholestyramine, guar gum, or activated charcoal, though evidence supporting their use is limited 1
• Correct vitamin K deficiency related to cholestasis, especially if using cholestyramine or rifampicin 1

Monitoring and Surveillance

Bile Acid Monitoring

• Measure serum bile acids at least weekly from 32 weeks' gestation to identify those with concentrations >40 μmol/L who are at increased risk of adverse pregnancy outcomes 1
• Monitor alterations in bile acid concentrations after UDCA treatment has been commenced, as this helps evaluate risk of adverse pregnancy outcomes 1
• Be aware that UDCA is also measured by enzymatic total serum bile acid assays, which may affect interpretation 1

Fetal Surveillance

• Begin antenatal fetal testing at the gestational age when delivery would be performed in response to abnormal results, or immediately if diagnosed later in gestation 2
• Increase frequency of testing with higher bile acid levels, especially ≥100 μmol/L 2
• Place all ICP patients on continuous fetal monitoring during labor due to increased stillbirth risk 2

Delivery Timing

Bile Acid-Guided Delivery Protocol

• For bile acids ≥100 μmol/L: deliver at 36 0/7 weeks of gestation due to increased stillbirth risk after 35 weeks 1, 2
• For bile acids <100 μmol/L: deliver between 36 0/7 and 39 0/7 weeks of gestation 1, 2
• For bile acids <40 μmol/L: consider delivery at term (39 weeks) 2

Critical Delivery Pitfall

• Never deliver before 37 weeks based on clinical suspicion alone without laboratory confirmation of elevated bile acids, as this causes iatrogenic prematurity-related morbidity 2, 3

Postpartum Management

Follow-Up Protocol

• ICP typically resolves completely after delivery 2
• If pruritus or abnormal liver tests persist beyond 6 weeks postpartum, refer to hepatology for evaluation of underlying hepatobiliary disease such as primary biliary cholangitis, primary sclerosing cholangitis, or ABCB4 deficiency 2, 3
• Persistence of symptoms suggests an underlying chronic liver condition that was unmasked by pregnancy 2

Counseling for Future Pregnancies

• Counsel patients about up to 90% recurrence risk in subsequent pregnancies 2
• All women with a history of ICP should be offered pre-pregnancy counseling from a team with expertise in managing these disorders 1

Multidisciplinary Approach

• Manage ICP patients with a multidisciplinary team that includes at minimum a physician, obstetrician, and midwife with expertise in the field 1
• If not available locally, refer to a center where this multidisciplinary approach can be implemented 1