What is the diagnosis and recommended treatment for a 32‑week pregnant woman with intense pruritus on the palms and soles, mild elevations in alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and elevated serum bile‑acid concentration?

Diagnosis and Treatment of Intrahepatic Cholestasis of Pregnancy at 32 Weeks

This patient has intrahepatic cholestasis of pregnancy (ICP), and you should immediately initiate ursodeoxycholic acid (UDCA) at 10–15 mg/kg/day in divided doses while measuring serum bile acids weekly to determine delivery timing. 1

Diagnosis

The clinical presentation is classic for ICP:

• Pruritus most intense on palms and soles without a primary rash (only excoriations from scratching) is pathognomonic for ICP 1
• Elevated serum bile acids (>10 μmol/L) combined with pruritus confirms the diagnosis 1
• Mildly elevated ALT and AST (typically <500 U/L) support the diagnosis but are not required 1, 2
• Onset at 32 weeks gestation fits the typical pattern, as 80% of ICP cases present after 30 weeks 1

Critical Differential Diagnoses to Exclude

Before finalizing the diagnosis, you must rule out life-threatening conditions:

• HELLP syndrome: Check for hemolysis, thrombocytopenia, and markedly elevated LDH (maternal mortality 1–25%) 2
• Acute fatty liver of pregnancy (AFLP): Look for hypoglycemia, coagulopathy, and marked hyperbilirubinemia (maternal mortality 7–18%) 2
• Pre-eclampsia: Screen for proteinuria and hypertension, as ICP carries a 2.6-fold increased risk 2

The absence of hemolysis, normal platelets, and normal LDH effectively exclude HELLP syndrome 2. The mild transaminase elevation and absence of coagulopathy or hypoglycemia argue against AFLP 1.

Immediate Management

Pharmacologic Treatment

Start UDCA 10–15 mg/kg/day in divided doses immediately 1, 2. This is the only first-line therapy with strong evidence (GRADE 1A) and provides:

• Relief of maternal pruritus (66.6% response rate vs 19% with cholestyramine) 3
• Reduction in bile acid levels by approximately 60% 3
• Protection against spontaneous preterm birth 1
• Possible reduction in stillbirth risk 1
• Improved neonatal outcomes including reduced respiratory distress syndrome and NICU admissions 2

If pruritus remains uncontrolled, titrate UDCA up to a maximum of 21–25 mg/kg/day 2. For refractory symptoms, add antihistamines (hydroxyzine), cholestyramine, rifampin, or S-adenosylmethionine as second-line agents 1, 4.

Weekly Bile Acid Monitoring

Measure serum bile acids (non-fasting) at least weekly from now until delivery 1. Bile acids can rise rapidly with advancing gestation, and the peak level determines delivery timing and fetal risk stratification 1.

Delivery Timing Algorithm (Risk-Stratified by Peak Bile Acid Level)

The bile acid concentration is the single most important factor determining delivery timing to prevent stillbirth:

Severe ICP (Bile Acids ≥100 μmol/L)

• Deliver at 36 0/7 weeks gestation (GRADE 1B) 1, 2
• Stillbirth risk increases 30-fold at this threshold, with risk rising markedly from 35 weeks onward 1
• Administer antenatal corticosteroids for fetal lung maturity if not already given 2

Moderate ICP (Bile Acids 40–99 μmol/L)

• Deliver between 36 0/7 and 39 0/7 weeks, favoring the earlier end (GRADE 1C) 1, 2
• This group has increased risks: preterm birth (RR 2.23), respiratory distress syndrome (RR 1.67), and meconium-stained fluid (RR 2.27) 2

Mild ICP (Bile Acids <40 μmol/L)

• Deliver between 37 0/7 and 39 0/7 weeks; targeting 39 weeks is reasonable 1, 2
• Minimal stillbirth risk in this group 1

Critical pitfall: Never deliver before 37 weeks based on clinical suspicion alone without documented elevated bile acids (GRADE 1B), as this exposes the neonate to unnecessary prematurity-related morbidity 2.

Fetal Surveillance

• Begin antenatal fetal testing immediately at 32 weeks, given the diagnosis at this gestational age 2
• Increase testing frequency as bile acids rise; for bile acids ≥100 μmol/L, perform twice-weekly or more frequent monitoring 2
• Apply continuous fetal monitoring during labor for all women with ICP, as fetal demise can occur suddenly through a non-placental mechanism that traditional surveillance may not predict 2

Postpartum Follow-Up

• Stop UDCA at delivery and taper gradually over 2–4 weeks if symptoms persist 1
• Repeat bile acids and liver enzymes at 4–6 weeks postpartum to confirm resolution 1, 5
• If pruritus or abnormal labs persist beyond 6 weeks, refer to hepatology immediately, as this indicates underlying chronic liver disease (not isolated ICP) 5, 6

Long-Term Risks

Women with ICP history face markedly elevated risks:

• Chronic hepatitis (HR 5.96) 6, 2
• Liver fibrosis/cirrhosis (HR 5.11) 6, 2
• Hepatitis C (HR 4.16) 6, 2
• Cholangitis (HR 4.2) 6, 2

Counsel the patient about a 40–90% recurrence risk in subsequent pregnancies 1, 6. Consider genetic testing for ABCB11, ABCB4, or ATP8B1 mutations if she has severe disease (bile acids >100 μmol/L), early onset, or recurrent ICP, as these variants may indicate progressive familial intrahepatic cholestasis or benign recurrent intrahepatic cholestasis 1, 4.