What is the diagnosis and treatment approach for pregnancy cholestasis?

Diagnosis and Management of Intrahepatic Cholestasis of Pregnancy

Diagnostic Approach

Diagnose intrahepatic cholestasis of pregnancy (ICP) based on pruritus occurring in the second or third trimester combined with total serum bile acid levels >10 μmol/L, and immediately measure both bile acids and liver transaminases (ALT/AST) in any pregnant woman presenting with pruritus. 1

Clinical Presentation

• Pruritus characteristics: Typically affects palms and soles, worsens at night, and occurs in late second or third trimester without a primary rash (only excoriations from scratching) 1, 2
• Absence of other symptoms: Dark urine, jaundice, excessive fatigue, insomnia, malaise, and abdominal pain are NOT typical of ICP and should prompt evaluation for alternative diagnoses 1
• Physical examination findings: No rash should be present other than scratch marks; presence of papules, plaques, bullae, jaundice, or dark urine suggests other hepatic diseases 1

Laboratory Testing

Order random (non-fasting) total serum bile acids and liver transaminases immediately when ICP is suspected - fasting samples are unnecessary as the difference between random and fasting values is clinically insignificant. 1, 2

• Bile acid levels: >10 μmol/L is diagnostic; enzymatic assay provides results in 4 hours to 4 days and is preferred over mass spectrometry (4-14 days) 1
• Transaminases: ALT and AST are typically elevated but not required for diagnosis; levels are usually <500 U/L in ICP 1, 2
• Bilirubin: Usually <6 mg/dL; mild jaundice occurs in only 10-15% of cases 1, 2
• Alkaline phosphatase: May be elevated but is less specific in pregnancy 1

Critical Diagnostic Pitfalls

If initial bile acids are normal but pruritus persists, repeat testing in 1-2 weeks because pruritus can precede bile acid elevation by several weeks. 1, 2

Never make treatment or delivery decisions based on clinical symptoms alone without laboratory confirmation of elevated bile acids. 1, 2

Differential Diagnosis to Exclude

Before confirming ICP, systematically exclude these conditions:

Pregnancy-specific emergencies (require immediate evaluation):

• Pre-eclampsia/HELLP syndrome: Check for hemolysis, elevated LDH, low platelets, hypertension, and proteinuria 2
• Acute fatty liver of pregnancy (AFLP): Assess coagulation studies, glucose, and look for third trimester presentation with higher bilirubin 2

Other hepatobiliary causes:

• Biliary obstruction/gallstones: Order hepatobiliary ultrasound 2
• Viral hepatitis: Check hepatitis serologies if risk factors present 1
• Primary biliary cholangitis or primary sclerosing cholangitis: Consider if elevated gamma-GT 2
• ABCB4 deficiency: Consider if presentation before second trimester 1

Non-hepatic causes of pruritus:

• Dermatologic conditions: Examine for primary skin lesions beyond excoriations 1
• Renal disease, thyroid disorders: Check renal function and thyroid function tests 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

• UDCA improves maternal pruritus, reduces bile acid levels, and decreases adverse outcomes including preterm birth and stillbirth 1
• Additional agents for refractory pruritus: cholestyramine or rifampicin 1

Fetal Surveillance

Begin antenatal fetal testing at the gestational age when you would perform delivery in response to abnormal results, or immediately if diagnosed later in gestation. 1

• The mechanism of stillbirth in ICP is thought to be sudden rather than chronic placental insufficiency, so traditional testing may not prevent all stillbirths 1
• Frequency of testing should increase with higher bile acid levels (especially ≥100 μmol/L) 1
• Place all ICP patients on continuous fetal monitoring during labor due to increased stillbirth risk 1

Delivery Timing (Critical Decision Point)

Delivery timing is determined strictly by total bile acid levels:

For bile acids ≥100 μmol/L:

• Deliver at 36 0/7 weeks of gestation because stillbirth risk increases substantially at this gestational age 1

For bile acids <100 μmol/L:

• Deliver between 36 0/7 and 39 0/7 weeks of gestation 1
• Consider delivery at term (39 weeks) for bile acids <40 μmol/L 1

Administer antenatal corticosteroids for fetal lung maturity if delivering before 37 0/7 weeks and not previously given. 1

Do NOT deliver before 37 weeks based solely on clinical diagnosis without laboratory-confirmed elevated bile acids. 1, 2

Risk Factors to Document

• Prior ICP (up to 90% recurrence risk in subsequent pregnancies) 2
• Family history of ICP (genetic susceptibility) 2
• Pre-existing hepatobiliary disease: hepatitis C (3.5× increased risk), cirrhosis (8.2× increased risk), gallstones (3.7× increased risk) 1, 2

Postpartum Follow-Up

If pruritus or abnormal liver tests persist beyond 6 weeks postpartum, refer to hepatology for evaluation of underlying hepatobiliary disease. 1, 2

ICP typically resolves completely after delivery; persistence suggests an underlying chronic liver condition that was unmasked by pregnancy 1