What is the most common cause of elevated liver function tests (LFTs) in a previously healthy pregnant female in her 20's?

Most Common Cause of Elevated LFTs in Pregnant Women in Their 20s

Intrahepatic cholestasis of pregnancy (ICP) is the most common pregnancy-specific liver disease causing elevated LFTs in young pregnant women, affecting 0.4%-10% of pregnancies, with the highest prevalence (up to 5.6%) among Latina women in the United States. 1

However, the overall most common cause depends critically on trimester and clinical context, as the differential diagnosis shifts dramatically throughout pregnancy.

Epidemiological Context by Trimester

First Trimester:

• Hyperemesis gravidarum causes abnormal LFTs in approximately 50% of affected patients and represents the most common cause of elevated transaminases in early pregnancy 2, 3
• One prospective study found hyperemesis gravidarum accounted for 55.8% of abnormal LFTs in the first trimester 4

Second Trimester:

• Viral hepatitis becomes the predominant cause, accounting for 47% of abnormal LFTs in one prospective series 4
• Metabolic dysfunction-associated steatotic liver disease (MASLD) affects at least 10% of women of childbearing age and represents the most common chronic liver disease in this population 1

Third Trimester:

• ICP is the most common pregnancy-specific cause, with 80% of cases presenting after 30 weeks gestation 1
• HELLP syndrome (28.3%) and acute fatty liver of pregnancy (AFLP, 14.8%) are also significant causes in the third trimester but less common than ICP 4

Key Diagnostic Algorithm

When evaluating elevated LFTs in a pregnant woman in her 20s, follow this systematic approach:

1. Determine gestational age - This immediately narrows the differential diagnosis 5, 6

2. Assess for pruritus - Generalized itching, especially on palms and soles without rash, strongly suggests ICP and warrants immediate bile acid measurement 1, 5

3. Measure serum bile acids - Total bile acids >10 μmol/L (non-fasting) confirms ICP, with levels >40 μmol/L indicating increased fetal risk 1, 5

4. Check blood pressure and proteinuria - Hypertension suggests preeclampsia spectrum disorders (preeclampsia, HELLP syndrome) rather than ICP 5, 7

5. Evaluate platelet count and hemolysis markers - Low platelets with hemolysis indicates HELLP syndrome 2, 3

6. Screen for viral hepatitis - Obtain HBsAg, anti-HCV, IgM anti-HEV, and IgM anti-HAV, especially in second trimester presentations 4

Critical Clinical Distinctions

ICP characteristics that distinguish it from other causes:

• Classic symptom is generalized pruritus without rash, most severe on palms and soles 1
• AST and ALT may be elevated 2-fold to 30-fold 1
• Bile acids are the most sensitive diagnostic marker, with most women without ICP having levels <10 μmol/L 1
• Postprandial bile acid measurements detect higher levels than fasting samples 1

MASLD as an underlying chronic condition:

• The incidence of MASLD in women of childbearing age is at least 10%, making it the most common chronic liver disease in this demographic 1
• MASLD increases risk of gestational diabetes (17% vs 7% in non-CLD pregnancies) and hypertensive complications (16% vs 3.8-3.9%) 1
• Women with known MASLD require increased surveillance using appropriate national screening protocols 1

Important Caveats and Pitfalls

Do not assume normal pregnancy changes:

• While alkaline phosphatase increases physiologically (up to 133-418 IU/L in third trimester), AST, ALT, bilirubin, and GGT should remain within non-pregnant reference ranges 5
• Albumin decreases normally in pregnancy, but this does not indicate liver dysfunction 5

Do not delay bile acid measurement:

• If initial bile acid testing is normal but pruritus persists, repeat testing is mandatory as pruritus can precede laboratory abnormalities 1, 5

Do not overlook medication history:

• Obtain detailed history of prescribed, over-the-counter, and herbal products, as drug-induced liver injury remains an important consideration 5

Recognize the severity spectrum:

• Abnormal LFTs occur in 3-5% of all pregnancies 2, 3, 6
• Pregnancy-specific conditions account for approximately 57.6% of abnormal LFTs overall 4
• Third trimester liver dysfunction carries the highest risk, with maternal mortality of 20.2% and perinatal mortality of 24.6% in severe cases 4

Management Implications

For confirmed ICP:

• Offer ursodeoxycholic acid (UDCA) for bile acids >40 μmol/L to treat maternal pruritus and reduce spontaneous preterm birth risk 1, 5
• Plan delivery at 35 weeks for bile acids >100 μmol/L due to intrauterine fetal demise risk of 3.4% 1, 5
• Continue UDCA throughout pregnancy as it is safe during pregnancy and breastfeeding 5

For MASLD:

• Implement lifestyle modifications including dietary advice 1
• Screen for gestational diabetes and hypertensive disease using appropriate national protocols 1
• Encourage breastfeeding postpartum 1