Intrahepatic Cholestasis of Pregnancy Management

Introduction

Intrahepatic cholestasis of pregnancy (ICP) is a condition characterized by pruritus, elevated serum bile acids, and mild to moderate elevations in liver enzymes, with diagnosis based on bile acids >10 μmol/L, total bilirubin <6 mg/dL, and clinical symptoms, as recommended by the American College of Gastroenterology and the American College of Obstetricians and Gynecologists 1, 2, 3, 4

Diagnosis of ICP requires measurement of serum bile acids and liver transaminase levels in patients with suspected ICP (GRADE 1B) 3

Women with ICP can be stratified into three risk categories based on bile acid levels:

Risk Category	Bile Acid Level	Recommended Delivery
High Risk	≥100 μmol/L	36 weeks or at diagnosis if after 36 weeks
Moderate Risk	40-99 μmol/L	36-39 weeks gestation
Lower Risk	<40 μmol/L	37-39 weeks gestation or at term

First-line treatment for ICP is Ursodeoxycholic acid (UDCA) at 10-15 mg/kg/day in divided doses (GRADE 1A) 3
Second-line options for refractory cases include rifampicin, anion exchange resins, and S-adenosyl-methionine, with monitoring for drug interactions, as recommended by the European Association for the Study of the Liver and the Journal of Hepatology guidelines 4, 5
Obeticholic acid should be avoided during pregnancy and lactation due to lack of safety data, as stated by the American Association for the Study of Liver Diseases 4
Fibrates may be used after the first trimester if benefits outweigh risks, according to the American Association for the Study of Liver Diseases 4
Vitamin K deficiency related to cholestasis should be corrected, as recommended by the American Association for the Study of Liver Diseases 4

Begin antenatal fetal surveillance at a gestational age when delivery would be performed in response to abnormal testing, or at diagnosis if made later in gestation (GRADE 2C) 3
Administer antenatal corticosteroids for fetal lung maturity if delivery occurs before 37 0/7 weeks (GRADE 1A) 3
Avoid preterm delivery at <37 weeks in patients with clinical diagnosis of ICP without laboratory confirmation of elevated bile acid levels (GRADE 1B) 3
High-risk patients (bile acids ≥100 μmol/L) should deliver at 36 0/7 weeks or at diagnosis if after 36 weeks, as recommended by the American College of Obstetricians and Gynecologists 3
Moderate-risk patients (bile acids 40-99 μmol/L) should deliver between 36 0/7 and 39 0/7 weeks, as recommended by the American College of Obstetricians and Gynecologists 3
Continuous fetal monitoring during labor is recommended due to the higher risk of stillbirth, according to the American College of Obstetricians and Gynecologists 3

The American College of Obstetricians and Gynecologists recommends stopping UDCA at delivery or gradually reducing over 2-4 weeks if symptoms persist, and ensuring bile acids, ALT/AST, and bilirubin normalize within 3 months postpartum 4
Ensure total serum bile acids, ALT/AST, and bilirubin return to normal within 3 months of delivery, and investigate for underlying liver disease if liver tests remain abnormal beyond 3 months, as recommended by the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases 4
The American College of Obstetricians and Gynecologists advises counseling patients regarding the high recurrence risk (up to 90%) in future pregnancies, need for preconception counseling, avoidance of estrogen-containing contraceptives, and importance of follow-up liver testing 3
The European Association for the Study of the Liver advises about increased risks in subsequent pregnancies, including gestational diabetes, hypertensive disorders, preterm birth, and fetal growth restriction, and recommends early bile acid testing in future pregnancies 4

Laparoscopic cholecystectomy is safe during pregnancy regardless of trimester, but ideally performed in the second trimester, according to the American Gastroenterological Association 2
Same-admission cholecystectomy for acute biliary pancreatitis reduces early readmission odds by 85%, as reported by the American Gastroenterological Association 2
For hemodynamically unstable patients or those at high surgical risk, percutaneous cholecystostomy tube placement or percutaneous gallbladder aspiration as "bridging" therapy may be considered, according to the American Gastroenterological Association 2
Radiation exposure should be minimized using modern fluoroscopy units with collimation and pulsed fluoroscopy, low radiation dose protocols, and low frame rates, as recommended by the American Gastroenterological Association 2
Patient positioning should take into account the trimester, with supine or prone position acceptable in the first trimester, and left pelvic tilt or left lateral position recommended in the second and third trimesters to avoid aorta/IVC compression, according to the American Gastroenterological Association 2
Safety measures including lead shielding of the pelvis, fetal monitoring by an obstetrician, thromboprophylaxis, and antibiotic prophylaxis when indicated should be taken, as recommended by the American Gastroenterological Association 2

Women with ICP are at increased risk for future hepatobiliary, immune-mediated, and cardiovascular diseases, with a 2.6-fold higher risk of preeclampsia, and higher rates of gestational diabetes and spontaneous and iatrogenic preterm birth 3
The American Association for the Study of Liver Diseases suggests considering referral for genetic counseling if there is a family history of ICP, severe or early-onset disease, or persistent liver abnormalities, as genetic variants in ABCB4, ABCB11, or ATP8B1 may indicate underlying chronic liver disease rather than isolated ICP 6