What are the treatment differences between primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC), and how is intrahepatic cholestasis of pregnancy (ICP) managed, particularly in relation to maternal pruritus?

Treatment Differences Between PBC and PSC, and Management of ICP-Related Pruritus

Primary Biliary Cirrhosis (PBC) vs Primary Sclerosing Cholangitis (PSC) Treatment

Ursodeoxycholic acid (UDCA) is the first-line treatment for both PBC and PSC, but with different efficacy profiles and dosing recommendations. 1, 2

PBC Treatment

• UDCA is the established first-line treatment at 13-15 mg/kg/day, with strong evidence for delaying histological progression to cirrhosis 1
• Obeticholic acid is the approved second-line therapy for PBC patients with incomplete response to UDCA, but should be discontinued during pregnancy and breastfeeding 3
• Fibrates may be used after the first trimester in pregnant women with PBC if benefits outweigh risks 3
• UDCA should be continued during pregnancy and breastfeeding in women with PBC 3, 1

PSC Treatment

• UDCA can be given at doses of 15-20 mg/kg/day in PSC, but with less robust evidence of efficacy than in PBC 3
• Endoscopic management is crucial in PSC for treating relevant bile duct strictures 3
• In pregnant women with PSC and worsening cholestasis, imaging with ultrasound or MRI is recommended to exclude obstruction by gallstones or high-grade strictures 3
• Endoscopic retrograde cholangiopancreatography (ERCP) can be performed for therapeutic interventions during the second or third trimester if needed 3

Intrahepatic Cholestasis of Pregnancy (ICP) Management

Diagnosis and Risk Assessment

• ICP is diagnosed based on pruritus with total serum bile acid levels >10 μmol/L 4
• Higher bile acid levels (≥100 μmol/L) correlate with increased risk of adverse fetal outcomes 4
• ICP is associated with increased rates of preterm birth, meconium-stained amniotic fluid, and fetal distress 3

Pharmacological Management of Maternal Pruritus

UDCA at 10-15 mg/kg/day is the first-line treatment for ICP-related pruritus and should be initiated promptly upon diagnosis. 3, 4

• UDCA effectively improves maternal pruritus symptoms, typically within 1-2 weeks 3, 4
• If pruritus is not relieved, the dose can be titrated up to a maximum of 21 mg/kg/day 3
• For refractory pruritus, additional options include:
  • Rifampicin (300-600 mg daily) can be combined with UDCA after the first trimester 3
  • Anion exchange resins (cholestyramine 4-8 g/day or colestipol 5-10 g/day), given at least 4 hours after UDCA 3
  • S-adenosyl-methionine may improve pruritus but is less effective than UDCA 3
  • Antihistamines such as diphenhydramine or hydroxyzine have limited benefit but may help with sleep 3
• Topical treatments like menthol creams and calamine lotion provide minimal relief as itching is typically widespread 3
• In severe cases of unbearable pruritus, plasmapheresis may provide transient relief 3, 1

General Measures for Pruritus Management

• Use emollients to prevent skin dryness 3
• Avoid hot baths or showers 3
• Use cooling gels for affected skin areas 3
• Keep nails shortened to minimize skin damage from scratching 3

Monitoring and Delivery Planning

• Serial bile acid measurements should guide management, particularly for delivery timing 4
• For patients with bile acid levels ≥100 μmol/L, delivery is recommended at 36 0/7 weeks or at diagnosis if after 36 weeks 4
• For patients with bile acid levels <100 μmol/L, delivery should occur between 36 0/7 and 39 0/7 weeks 4
• For patients with bile acid levels <40 μmol/L, consider delivery at term 4

Special Considerations

Pregnancy in PBC and PSC

• Pregnancy is generally well-tolerated in non-cirrhotic patients with PBC and PSC 3, 5
• Pruritus may worsen during pregnancy in women with PBC or PSC 3, 1
• Pregnant patients with portal hypertension should be endoscoped in the second trimester 1
• Pregnant patients with PBC should be screened for anti-Ro and anti-La antibodies 3, 1
• Women with PSC have higher rates of preterm births (16.3% vs. 5.1%) and Caesarean delivery (29.4% vs. 13.3%) 3
• Maternal serum ALT at booking and bile acid concentration during pregnancy negatively correlate with gestation at birth 5

Post-Delivery Management

• UDCA treatment for ICP should be discontinued at delivery 4
• If symptoms or abnormal liver tests persist for 4-6 weeks after delivery, further investigation for underlying chronic liver diseases is warranted 4

Vitamin K Supplementation

• Cholestasis and the use of anion exchange resins or rifampicin may exacerbate vitamin K deficiency 3
• Vitamin K replacement should be given to women with steatorrhea or confirmed vitamin K deficiency 3
• Monitoring coagulation tests (e.g., INR) is reasonable in women treated with these drugs 3
• Neonates of women treated with rifampicin should receive vitamin K 3