What is the treatment of choice for Pregnancy-Induced Intrahepatic Cholestasis (PIIC)?

Treatment of Pregnancy-Induced Intrahepatic Cholestasis

Ursodeoxycholic acid (UDCA) at 10-15 mg/kg/day is the first-line treatment of choice for intrahepatic cholestasis of pregnancy, initiated immediately upon diagnosis. 1, 2

Primary Pharmacological Treatment

UDCA Dosing and Administration

• Start UDCA at 10-15 mg/kg/day, divided into 2-3 daily doses (typical regimens: 300 mg twice or three times daily, or 500 mg twice daily) 1, 2
• If pruritus persists after 1-2 weeks, titrate up to a maximum of 21-25 mg/kg/day 1, 2
• Clinical improvement in pruritus typically occurs within 1-2 weeks, while biochemical improvement takes 3-4 weeks 1, 2
• UDCA is well-tolerated, with mild nausea and dizziness reported in up to 25% of patients 1

Evidence for UDCA Efficacy

• UDCA improves maternal pruritus, reduces serum bile acids, and normalizes liver enzymes 1
• For women with bile acids >40 μmol/L, UDCA reduces the risk of spontaneous preterm birth and may protect against stillbirth 1, 2
• Meta-analyses demonstrate UDCA reduces preterm birth (risk ratio 0.56), fetal distress (risk ratio 0.68), respiratory distress syndrome (risk ratio 0.33), and NICU admissions (risk ratio 0.55) 1
• UDCA protects against bile acid-induced fetal cardiac arrhythmias and abnormal heart rate variability 1

Alternative and Adjunctive Therapies

Second-Line Options for Refractory Pruritus

When UDCA alone fails to control symptoms:

• Rifampicin can be combined with UDCA for refractory cases, though it may cause hepatotoxicity in 5% of patients 1
• Cholestyramine (anion exchange resin) has limited efficacy for pruritus but can be considered, separated from UDCA by at least 4 hours 1
• S-adenosyl-methionine may improve pruritus but is less effective than UDCA 1, 2
• Antihistamines (diphenhydramine, hydroxyzine) have limited benefit but can be tried 1
• Topical antipruritics (menthol creams, calamine lotion) provide minimal relief as itching is typically widespread 1, 3

Critical Caveat for Alternative Therapies

• Cholestyramine and rifampicin may exacerbate vitamin K deficiency—monitor INR and provide vitamin K replacement in women with steatorrhea or confirmed deficiency 1, 3
• Neonates of mothers treated with rifampicin should receive vitamin K at birth 1, 3

Delivery Timing Based on Bile Acid Levels

The timing of delivery should be risk-stratified by total serum bile acid concentration:

• Bile acids ≥100 μmol/L: Deliver at 36 weeks or at diagnosis if after 36 weeks (highest stillbirth risk after 35 weeks) 1, 2
• Bile acids <100 μmol/L: Deliver between 36-39 weeks of gestation 1, 2
• Bile acids <40 μmol/L: Consider delivery at term 1, 2
• Administer antenatal corticosteroids for fetal lung maturity if delivery occurs before 37 weeks 2

Monitoring Strategy

• Check non-fasting serum bile acids at least weekly, as levels may continue to rise with advancing gestation 1
• Monitor liver function tests (ALT, AST, bilirubin) to guide treatment response 1, 2
• Begin antepartum fetal surveillance at a gestational age when delivery would be performed in response to abnormal testing 2

Post-Delivery Management

• Discontinue UDCA at delivery 3, 2
• Pruritus typically resolves within days to weeks postpartum 1
• If symptoms or abnormal liver tests persist for 4-6 weeks after delivery, investigate for underlying chronic liver disease (PBC, PSC, viral hepatitis) 1, 3, 2

Important Clinical Pitfalls

• Do not delay UDCA initiation while awaiting bile acid results if clinical suspicion is high—treatment improves both maternal symptoms and fetal outcomes 1
• Bilirubin is rarely markedly elevated in ICP—if significantly elevated or persistent, investigate alternative diagnoses 1
• ICP increases risk of preeclampsia by approximately 5-fold, typically occurring 2-4 weeks after ICP diagnosis 1
• The largest placebo-controlled trial (n=605) showed UDCA improved maternal pruritus but did not demonstrate perinatal benefit in the context of modern fetal surveillance and planned early delivery, though meta-analyses support fetal benefits 1