What is the initial approach to a pregnant patient with hepatomegaly (enlarged liver) and normal liver enzymes?

Initial Approach to Hepatomegaly with Normal Liver Enzymes in Pregnancy

Begin with hepatic ultrasound immediately to characterize the hepatomegaly and identify any focal lesions, as this is the safest and most informative first-line imaging modality in pregnancy. 1, 2

Immediate Diagnostic Workup

Essential History and Physical Examination

• Gestational age determination is critical, as pregnancy-specific liver diseases occur in predictable timeframes (hyperemesis gravidarum in first trimester, intrahepatic cholestasis of pregnancy typically after 30 weeks, HELLP syndrome between 27-37 weeks, acute fatty liver of pregnancy in third trimester). 1
• Assess for pruritus, which may indicate intrahepatic cholestasis of pregnancy even before liver enzymes become abnormal. 1
• Document right upper quadrant or epigastric pain, which could suggest HELLP syndrome complications (hepatic hemorrhage, infarct, or rupture) even with normal transaminases initially. 3
• Evaluate for signs of pre-eclampsia (hypertension, proteinuria, headache, visual changes), as 85% of HELLP syndrome cases have hypertension. 3
• Screen for hepatic encephalopathy signs (confusion, asterixis), which if present is highly suspicious for acute fatty liver of pregnancy over other diagnoses. 3

Critical Laboratory Testing

While liver enzymes are currently normal, the following tests are essential because normal aminotransferases do not exclude serious pregnancy-related liver disease: 1

• Total serum bile acids (non-fasting): Elevation >10 μmol/L indicates intrahepatic cholestasis of pregnancy even with normal transaminases. 1
• Complete blood count with platelet count: Thrombocytopenia suggests HELLP syndrome; markedly reduced platelets correlate with higher risk of hepatic hemorrhage. 3
• Coagulation profile (PT/INR, fibrinogen): Prolonged PT and reduced fibrinogen are characteristic of acute fatty liver of pregnancy. 3
• Glucose and ammonia levels: Hypoglycemia and elevated ammonia suggest acute fatty liver of pregnancy. 3
• Bilirubin: Any elevation is abnormal in pregnancy and requires investigation. 1

Imaging Strategy

First-Line Imaging

Abdominal ultrasound without Doppler is the imaging modality of choice given lack of ionizing radiation and absence of known fetal risks. 1, 2

• Doppler interrogation of hepatic vasculature can be safely conducted in all trimesters but exposure time should be minimized. 1
• Ultrasound can identify: focal lesions (hemangiomas, adenomas, focal nodular hyperplasia), steatosis, biliary obstruction, hepatic hemorrhage or hematoma, and structural abnormalities. 2

Advanced Imaging When Ultrasound is Inadequate

MRI without gadolinium is the preferred modality if further characterization is needed, as it is safe in all trimesters. 1, 2

• Avoid gadolinium-based contrast throughout pregnancy, as gadolinium crosses the placenta and accumulates in the fetal urinary tract. 1
• CT abdomen should be reserved for suspected hepatic hemorrhage, infarct, or rupture in HELLP syndrome, particularly with severe persistent right upper quadrant pain. 3

Differential Diagnosis Framework

Pregnancy-Specific Causes (Even with Normal Enzymes Initially)

• Intrahepatic cholestasis of pregnancy: May present with hepatomegaly and pruritus before transaminase elevation; diagnosis requires bile acids >10 μmol/L. 1
• Early HELLP syndrome: Can present with hepatomegaly before marked transaminase elevation; look for thrombocytopenia and hemolysis. 3
• Acute fatty liver of pregnancy: Typically third trimester; hepatomegaly may precede marked enzyme elevation; check coagulation profile, glucose, and ammonia. 3

Pre-Existing Liver Conditions

• Hepatic adenomas: Pregnancy does not increase complication risk for adenomas <5 cm, but ultrasound monitoring is required as 25.5% may grow during pregnancy. 4, 2
• Giant hemangiomas (>10 cm): Require trimester-by-trimester ultrasound monitoring due to 5% rupture risk. 2
• Focal nodular hyperplasia: Pregnancy is not contraindicated and carries no increased risk. 2
• Metabolic dysfunction-associated steatotic liver disease (MASLD): Common cause of hepatomegaly; implement lifestyle modifications. 2
• Autoimmune hepatitis: May become symptomatic during pregnancy; continue immunosuppression with prednisolone, budesonide, and thiopurines. 2, 5
• Cirrhosis with portal hypertension: Continue or initiate beta-blockers for variceal prophylaxis; maintain hepatocellular carcinoma surveillance. 2

Coincidental Conditions

• Gallstone disease: Common in women of childbearing age and promoted by pregnancy; ultrasound will identify. 5
• Viral hepatitis: Check hepatitis B and C serology; hepatitis E has poor prognosis in pregnancy. 5
• Primary biliary cholangitis: May become symptomatic during pregnancy; check anti-mitochondrial antibody. 1

Ongoing Monitoring Strategy

Serial Laboratory Testing

• Repeat liver enzymes, bilirubin, and bile acids every 2-3 weeks before 32 weeks' gestation, then at least weekly until delivery if hepatomegaly persists or symptoms develop. 1
• Weekly coagulation profiles if acute fatty liver of pregnancy or HELLP syndrome is suspected. 3

Serial Imaging

• Ultrasound surveillance each trimester for high-risk lesions (large hemangiomas >10 cm, hepatocellular adenomas >5 cm, exophytic lesions). 2
• Immediate repeat imaging if new symptoms develop (pain, bleeding, hemodynamic instability). 3

Critical Pitfalls to Avoid

• Do not assume normal liver enzymes exclude serious disease: Intrahepatic cholestasis of pregnancy, early HELLP syndrome, and acute fatty liver of pregnancy can present with hepatomegaly before marked transaminase elevation. 1, 3
• Do not defer imaging: Ultrasound is safe throughout pregnancy and should be performed promptly to characterize hepatomegaly. 1, 2
• Do not miss bile acid testing: This is the most sensitive test for intrahepatic cholestasis of pregnancy and may be elevated when transaminases are normal. 1
• Do not discontinue immunosuppression in autoimmune hepatitis: Treatment continuation improves both maternal and fetal outcomes. 2

When to Escalate Care

Immediate transfer to a transplant center is indicated for: 3

• HELLP syndrome complicated by hepatic rupture or acute liver failure
• Acute fatty liver of pregnancy with hepatic encephalopathy or coagulopathy
• Any evidence of hepatic hemorrhage or infarction on imaging

Multidisciplinary team involvement (hepatologist, maternal-fetal medicine specialist, anesthetist, neonatologist) should be engaged for any pregnant patient with hepatomegaly and concerning features, even with normal liver enzymes. 1, 6