What are the management and treatment options for pregnant women with high bile acids or biliary cholelithiasis, including the use of Actigall (ursodiol)?

Management of High Bile Acids, Biliary Cholelithiasis, and Actigall in Pregnancy

Ursodeoxycholic acid (Actigall) at a dose of 10-15 mg/kg/day is the first-line treatment for intrahepatic cholestasis of pregnancy and should be offered to pregnant women with elevated bile acids >10 μmol/L and pruritus. 1, 2

Intrahepatic Cholestasis of Pregnancy (ICP)

Diagnosis

• Diagnosis based on:
  • Pruritus (typically in second or third trimester)
  • Serum bile acid levels >10 μmol/L
  • Mild to moderate elevations in liver enzymes (up to 10-20 times upper limit of normal)
  • Serum total bilirubin <6 mg/dL

Risk Stratification by Bile Acid Levels

• High risk (≥100 μmol/L):

  • Highest risk of intrauterine fetal demise
  • Deliver at 36 weeks or at diagnosis if after 36 weeks
  • More frequent fetal monitoring recommended

• Moderate risk (40-99 μmol/L):

  • Deliver between 36-39 weeks gestation

• Lower risk (<40 μmol/L):

  • Deliver between 37-39 weeks gestation
  • Consider delivery at term

Treatment

1. First-line: Ursodeoxycholic acid (Actigall)

   • Dosage: 10-15 mg/kg/day in divided doses
   • Benefits: Improves maternal pruritus, reduces serum bile acids and liver enzymes
   • Decreases adverse outcomes including preterm birth and stillbirth 1, 2
   • Safe in pregnancy and breastfeeding 1

2. Second-line options for refractory cases:

   • Rifampicin (300-600 mg daily) 1
   • Anion exchange resins (cholestyramine 4-8 g/day or colestipol 5-10 g/day)
     • Must be given at least 4 hours after ursodeoxycholic acid 1
     • Monitor for vitamin K deficiency 1

Monitoring

• Regular measurement of total serum bile acids
• Monitor liver function tests
• Antenatal testing should begin when delivery would be performed in response to abnormal results
• More frequent monitoring for bile acids ≥100 μmol/L

Biliary Cholelithiasis in Pregnancy

Management Approach

• Symptomatic cholelithiasis during pregnancy can be managed medically or surgically
• Medical management has higher rates of symptomatic relapse (38%) 3
• Surgical management (laparoscopic cholecystectomy) is safe during any trimester of pregnancy 1
• After first trimester, patients should be placed in left lateral or partial left lateral decubitus position for laparoscopy to minimize inferior vena cava compression 1

Surgical Considerations

• Laparoscopic cholecystectomy should be considered for:
  • Complicated non-resolving biliary tract disease
  • Recurrent symptoms despite medical management
• Surgery is preferably performed during the second trimester 4
• Surgical management decreases hospital stays and reduces rates of labor induction and preterm deliveries 3

Postpartum Management

Follow-up

• Pruritus typically resolves within days after delivery
• Liver function tests and bile acids should normalize within 2-4 weeks
• If abnormalities persist beyond 3 months, investigate for underlying liver disease 2

Warning Signs

• Postpartum deterioration of liver function can occur in up to 70% of women with pre-existing cholestatic diseases 2
• Seek immediate medical attention for jaundice, severe abdominal pain, or signs of coagulopathy

Drug Interactions and Precautions with Actigall (Ursodiol)

• Drug interactions:

  • Bile acid sequestering agents (cholestyramine, colestipol) may reduce ursodiol absorption 5
  • Aluminum-based antacids may interfere with ursodiol action 5
  • Estrogens, oral contraceptives, and lipid-lowering drugs may counteract ursodiol effectiveness 5

• Safety in pregnancy:

  • Reproduction studies in rats and rabbits showed no evidence of fetal harm at therapeutic doses 5
  • Inadvertent exposure of 4 women in first trimester showed no evidence of effects on fetus or newborn 5
  • Not recommended for use during pregnancy according to FDA labeling, but clinical guidelines support its use for ICP 1, 2, 5

By following these evidence-based recommendations, clinicians can effectively manage high bile acids and biliary cholelithiasis in pregnant women, reducing maternal symptoms and minimizing risks to both mother and fetus.