Differential Diagnosis Beyond Intrahepatic Cholestasis of Pregnancy
The most critical pregnancy-specific differential diagnoses to exclude in this patient are pre-eclampsia/HELLP syndrome and acute fatty liver of pregnancy (AFLP), both of which can present with elevated liver enzymes and carry significant maternal and fetal mortality risks. 1
Pregnancy-Specific Conditions (Priority Differentials)
HELLP Syndrome
- Characterized by hemolysis, elevated liver enzymes, and low platelets 1
- Occurs in 0.2-0.6% of pregnancies, typically in third trimester or postpartum 1
- Associated with pre-eclampsia in most cases - check blood pressure, proteinuria, and signs of end-organ damage 1
- Laboratory findings: Elevated LDH (indicating hemolysis), thrombocytopenia, elevated transaminases 2
- Critical distinction: HELLP has elevated LDH and low platelets, which are NOT features of ICP 2
Acute Fatty Liver of Pregnancy (AFLP)
- Rare but life-threatening condition occurring in 0.005-0.01% of pregnancies 1
- Presents in third trimester or postpartum with elevated liver enzymes and bilirubin 1
- Associated with pre-eclampsia in 50% of cases 1
- More severe presentation than ICP: Transaminases often >500 U/L (vs. <500 U/L in ICP), bilirubin often >5 mg/dL 2
- May present with hypoglycemia, coagulopathy, encephalopathy, and acute liver failure
Non-Pregnancy-Specific Conditions to Consider
Chronic Liver Diseases
If cholestasis persists after delivery or presents atypically, consider underlying chronic conditions: 1
- Primary biliary cholangitis (PBC) - can be unmasked by pregnancy 1
- Primary sclerosing cholangitis (PSC) - may present with pruritus during late pregnancy 1
- ABCB4 deficiency - genetic transporter defect, particularly if gamma-GT is elevated 1
- Chronic hepatitis C - can develop pruritus during pregnancy 1
Other Systemic Causes of Pruritus Without Rash
The Society for Maternal-Fetal Medicine identifies multiple non-hepatic causes: 1
- Renal disease: Chronic renal failure can cause pruritus and abnormal liver tests 1
- Thyroid disorders: Both hypo- and hyperthyroidism 1
- Hematologic malignancies: Hodgkin disease, leukemia, non-Hodgkin lymphoma, polycythemia rubra vera 1
- Infections: HIV, parasitosis, helminthosis 1
- Malabsorption syndromes 1
- Drug-induced: Hydrochlorothiazide, opioids 1
Biliary Tract Disease
- Choledocholithiasis/gallstones: Up to 10% of pregnant women develop stones or sludge during pregnancy 1
- Requires ultrasound evaluation to exclude obstructive cholestasis 1
Diagnostic Algorithm
Step 1: Exclude life-threatening pregnancy-specific conditions
- Check complete blood count for hemolysis and thrombocytopenia (HELLP) 2
- Measure LDH (elevated in HELLP, normal in ICP) 2
- Assess for pre-eclampsia: blood pressure, proteinuria, symptoms 1
- Check coagulation studies and glucose (AFLP) 1
Step 2: Confirm ICP diagnosis
- Bile acids >11 μmol/L are diagnostic 2, 3
- Transaminases typically <500 U/L 2
- Bilirubin typically <5 mg/dL 2
- Gamma-GT usually normal (unless ABCB4 variant) 1
Step 3: Evaluate for non-pregnancy causes
- Hepatobiliary ultrasound to exclude gallstones/biliary obstruction 1
- Viral hepatitis serologies (if not already done) 3
- Thyroid function tests 1
- Renal function tests 1
Critical Clinical Pitfalls
Do not assume ICP without excluding HELLP/AFLP - these conditions require immediate delivery and carry maternal mortality risk, whereas ICP management is more conservative 1
Elevated albumin is unusual - albumin typically decreases in pregnancy; if truly elevated, consider laboratory error or hemoconcentration from pre-eclampsia 1
Skin examination is essential - excoriations from scratching can be mistaken for primary dermatologic conditions like atopic eruption of pregnancy (AEP), polymorphic eruption of pregnancy (PEP), or pemphigoid gestationis 1
Plan for post-delivery follow-up - if abnormalities persist beyond 4-6 weeks postpartum, investigate for underlying chronic liver disease (PBC, PSC, ABCB4 deficiency, chronic hepatitis C) 1