How should intrahepatic cholestasis of pregnancy be diagnosed and managed in a second‑trimester pregnant woman presenting with intense pruritus on the palms and soles, elevated serum total bile acids (≥10 µmol/L) and abnormal liver function tests?

Diagnosis and Management of Intrahepatic Cholestasis of Pregnancy

Initiate ursodeoxycholic acid (UDCA) 10–15 mg/kg/day in divided doses immediately upon confirming elevated serum bile acids >10 µmol/L, and plan delivery at 36 0/7 weeks if bile acids reach ≥100 µmol/L or between 36–39 weeks for lower levels. 1, 2

Diagnostic Confirmation

Your patient presents with the classic triad: intense pruritus on palms and soles (pathognomonic location), elevated bile acids ≥10 µmol/L, and abnormal liver function tests. 1, 2 This confirms intrahepatic cholestasis of pregnancy. 1

Key diagnostic features to document:

• Pruritus characteristics: Generalized itching predominantly affecting palms and soles, worse at night, without a primary rash (only excoriations from scratching). 1, 2
• Timing: Onset in second trimester is earlier than the typical presentation (80% present after 30 weeks), which may indicate more severe disease. 1, 2
• Laboratory confirmation: Serum total bile acids >10 µmol/L is diagnostic when combined with pruritus; elevated transaminases support the diagnosis but are not required. 1, 2

Critical exclusions before confirming ICP:

• Rule out HELLP syndrome and acute fatty liver of pregnancy immediately—check complete blood count with platelets, coagulation studies, and glucose. 2 These conditions carry maternal mortality risks of 1–25% and 7–18% respectively and require immediate delivery. 2
• Assess for preeclampsia (2.6-fold increased risk with ICP)—check blood pressure and proteinuria, as proteinuria typically precedes hypertension. 2
• Perform hepatobiliary ultrasound to exclude gallstones and biliary obstruction. 2
• Dark urine and jaundice are uncommon in ICP (only 10–15% develop mild jaundice with bilirubin <5 mg/dL); if present, investigate alternative hepatic diseases urgently. 1, 2

Immediate Pharmacologic Management

Start UDCA 10–15 mg/kg/day divided into 2–3 doses today. 1, 2, 3 This is GRADE 1A evidence—the strongest recommendation level. 2 UDCA reduces maternal pruritus, lowers bile acid concentrations, decreases spontaneous preterm birth, and may reduce stillbirth risk. 1, 2, 3

If pruritus remains uncontrolled after 1–2 weeks, titrate UDCA up to 21–25 mg/kg/day. 2, 3

Second-line adjuncts for refractory symptoms:

• Cholestyramine 4–16 g daily in divided doses, separated by 2–4 hours from UDCA to avoid binding interactions. 3 Monitor prothrombin time regularly and supplement vitamin K if prolonged, as cholestyramine can worsen vitamin K deficiency and cause coagulopathy. 3
• Rifampin 300–600 mg daily carries a 12% risk of drug-induced hepatitis in cholestatic patients and requires hepatic monitoring. 3
• Antihistamines provide minimal benefit but may be tried for nighttime relief. 3

Maternal Monitoring Protocol

Measure serum bile acids weekly from now until delivery. 2, 3 Bile acid levels can rise rapidly, particularly near term, and the peak level determines delivery timing and fetal risk stratification. 2, 3

Screen for spontaneous preterm labor: Elevated bile acids activate myometrial oxytocin receptors, increasing spontaneous preterm birth risk 2.23-fold. 2

Fetal Surveillance Strategy

Begin antenatal fetal testing immediately (since you're already in the second trimester when delivery decisions may be needed). 1, 2, 3 The frequency of testing should increase as bile acid levels rise—for bile acids ≥100 µmol/L, twice-weekly or more frequent monitoring is advised because stillbirth hazard increases approximately 30-fold. 2

Apply continuous fetal monitoring during labor for all women with ICP, as fetal demise can occur suddenly through a non-placental mechanism even after recent reassuring testing. 1, 2, 3

Critical pitfall: Normal fetal testing does not eliminate stillbirth risk in ICP. 2 Traditional fetal surveillance is less predictive because ICP-related stillbirth occurs suddenly, not through gradual placental insufficiency. 2

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

This is the most critical management decision and must be based on laboratory values, not clinical suspicion alone.

Severe ICP (Bile Acids ≥100 µmol/L)

Plan delivery at 36 0/7 weeks of gestation. 1, 2, 3 This is GRADE 1B evidence. 1, 2 Stillbirth risk rises approximately 30-fold at this threshold, with intrauterine fetal demise prevalence of 3.4%. 1, 2 Administer antenatal corticosteroids for fetal lung maturity if not already given. 2

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

Schedule delivery between 36 0/7 and 39 0/7 weeks, favoring the earlier end of this window. 1, 2, 3 This is GRADE 1C evidence. 2 This range is associated with increased risks: preterm birth (RR 2.23), respiratory distress syndrome (RR 1.67), and meconium-stained amniotic fluid (RR 2.27). 2

Mild ICP (Bile Acids <40 µmol/L)

Aim for delivery between 37 0/7 and 39 0/7 weeks; targeting 39 weeks is reasonable. 1, 2, 3 Stillbirth risk is minimal in this group (0.1% prevalence), and fetal outcomes are similar to women without ICP. 1, 2

Absolute Contraindication

Never deliver before 37 weeks based solely on clinical suspicion without documented elevated bile acids. 1, 2, 3 This is GRADE 1B evidence. 1, 2 Premature delivery without laboratory confirmation exposes the neonate to unnecessary prematurity-related morbidity. 2, 3

Postpartum Follow-Up

Discontinue UDCA at delivery or taper gradually over 2–4 weeks if pruritus persists postpartum. 2, 3

Repeat serum bile acids and liver transaminases at 4–6 weeks postpartum to confirm resolution. 1, 2, 3 ICP typically resolves completely within days to weeks after delivery. 1

Refer to hepatology if symptoms or laboratory abnormalities persist beyond 6 weeks postpartum. 2, 3 Persistence indicates possible underlying chronic hepatobiliary disease rather than isolated ICP. 1, 2

Consider genetic testing for ABCB11, ABCB4, or ATP8B1 mutations given your patient's early onset (second trimester) and elevated bile acids. 1, 2 Women with severe ICP (bile acids ≥100 µmol/L), recurrent ICP, or early-onset ICP have increased likelihood of these genetic variants. 1 Identification is relevant because some may have risk for progressive liver disease, gallstones, cholangitis, and possibly liver cancer. 1

Long-Term Maternal Risks and Counseling

Counsel regarding 40–90% recurrence risk in subsequent pregnancies. 1, 2, 3 This reflects a strong genetic component. 2

Women with ICP history have markedly elevated long-term hepatobiliary risks:

• Chronic hepatitis (hazard ratio 5.96) 2, 3
• Liver fibrosis/cirrhosis (HR 5.11) 2, 3
• Hepatitis C infection (HR 4.16) 1, 2, 3
• Cholangitis (HR 4.20) 2

These associations may reflect underlying chronic liver disease being unmasked by pregnancy or genetic variants conferring different risk profiles. 1

Common Clinical Pitfalls

Do not assume ICP is excluded with one normal bile acid level if pruritus persists. 4 Pruritus can precede laboratory abnormalities by several weeks. 1 If initial bile acid testing is normal but symptoms continue, repeat testing in 1–2 weeks. 1, 4

Do not initiate routine antenatal surveillance in patients with pruritus but persistently normal bile acids (GRADE 2C), as evidence does not show increased fetal risk in this subgroup. 2

Do not mistake excoriations from scratching for a primary rash. 1, 2 ICP is not associated with a primary rash; the intensity of pruritus leads to excoriations or prurigo nodularis that may be mistaken for dermatologic conditions. 1