What causes elevated liver function tests (LFTs) during pregnancy?

Causes of Elevated Liver Function Tests During Pregnancy

Elevated liver function tests during pregnancy are primarily caused by pregnancy-specific liver disorders, but can also result from pre-existing or coincidental liver diseases, requiring prompt investigation to reduce maternal and fetal morbidity and mortality. 1

Pregnancy-Specific Liver Disorders

First Trimester

• Hyperemesis Gravidarum
  • Characterized by intractable vomiting leading to dehydration
  • Affects up to 50% of patients with liver dysfunction in first trimester 2
  • Typically presents with mild transaminase elevations

Second and Third Trimester

• Intrahepatic Cholestasis of Pregnancy (ICP)

  • Characterized by pruritus and elevated bile acids
  • Usually presents after 30 weeks but can occur earlier 1
  • Laboratory findings: elevated total serum bile acids and transaminases
  • Requires monitoring of bile acids and consideration of early delivery if levels exceed 100 μmol/L 3

• Preeclampsia and HELLP Syndrome

  • Occurs after 20 weeks gestation 3
  • Features: hypertension, proteinuria, elevated liver enzymes
  • HELLP syndrome includes hemolysis, elevated liver enzymes, and low platelets
  • Most common cause of hepatic tenderness and liver dysfunction in late pregnancy 4
  • Accounts for 28.3% of third-trimester liver dysfunction 2

• Acute Fatty Liver of Pregnancy (AFLP)

  • Rare but catastrophic condition (0.01% of pregnancies) 1
  • Typically occurs in third trimester
  • Characterized by microvesicular fatty infiltration of hepatocytes
  • Can progress to acute liver failure with coagulopathy and encephalopathy
  • Accounts for 14.8% of third-trimester liver dysfunction 2
  • Requires immediate delivery for maternal and fetal survival 4

Pre-existing and Coincidental Liver Diseases

Viral Hepatitis

• Most common cause of abnormal LFTs in second trimester (47%) 2
• Includes hepatitis A, B, C, and E
• Requires serological testing (HBsAg, anti-HCV, IgM anti-HEV, IgM anti-HAV) 2

Gallstone Disease

• Pregnancy increases risk of gallstone formation due to decreased gallbladder motility 1
• Can cause biliary colic, cholecystitis, or choledocholithiasis with elevated LFTs

Autoimmune Liver Disease

• Pre-existing autoimmune hepatitis may flare during pregnancy or postpartum
• Requires continued immunosuppressive therapy throughout pregnancy 3

Non-alcoholic Fatty Liver Disease (NAFLD)

• Found in 16-18% of pregnant women 5
• Associated with obesity, diabetes, and metabolic syndrome
• May explain many cases of "idiopathic" abnormal liver function in pregnancy 5
• Increases risk of pregnancy complications and abnormal fetal growth

Drug-Induced Liver Injury

• Careful medication history is essential
• Prescribed, over-the-counter medications, and herbal products should be reviewed 1

Diagnostic Approach

Initial Laboratory Evaluation

• Complete blood count with platelets
• Comprehensive metabolic panel
• Coagulation studies
• Total serum bile acids
• Hepatitis serologies 3

Imaging

• Ultrasound is first-line and safest option in pregnancy
• MRI without contrast if further evaluation is needed 3
• Avoid CT due to radiation exposure

Important Considerations

Normal vs. Abnormal Values

• Any elevation in aminotransferases, bilirubin, or bile acids during pregnancy is abnormal and requires investigation 1
• Normal physiological changes in pregnancy include:
  • Increased alkaline phosphatase (placental origin)
  • Decreased albumin (hemodilution)
  • Increased alpha-fetoprotein 1

Clinical Pitfalls

• Delayed diagnosis can lead to increased maternal and fetal morbidity and mortality
• Attributing all liver enzyme elevations to pregnancy without considering non-pregnancy related causes
• Failure to monitor bile acid levels in ICP
• Inadequate postpartum follow-up 3

Timing of Presentation

Understanding the typical timing of pregnancy-specific liver disorders helps narrow the differential diagnosis:

• First trimester: Hyperemesis gravidarum
• Second trimester: Viral hepatitis, early ICP
• Third trimester: ICP, preeclampsia/HELLP, AFLP 1

Postpartum Follow-up

• Essential to ensure resolution of pregnancy-related liver diseases
• Persistent abnormalities beyond 6 weeks postpartum warrant evaluation for underlying chronic liver disease 1

Abnormal liver function tests in pregnancy affect 3-5% of pregnancies and require prompt and thorough evaluation to distinguish between pregnancy-specific disorders and coincidental liver diseases to guide appropriate management and improve maternal and fetal outcomes 6.