How to approach deranged liver function tests (LFTs) in pregnant females?

Approach to Deranged Liver Function Tests in Pregnant Females

A systematic, algorithmic approach to deranged liver function tests (LFTs) in pregnant women is essential, focusing on trimester-specific causes and pregnancy-specific liver disorders to reduce maternal and fetal morbidity and mortality. 1, 2

Initial Assessment

Recognize Normal Physiologic Changes in Pregnancy

• Albumin: Decreases to 28-37 g/L (normal: 35-46 g/L)
• Alkaline phosphatase (ALP): Increases significantly (up to 3x normal) due to placental production
• GGT: Decreases to 3-41 IU/L (normal: 11-50 IU/L)
• Bilirubin: Typically remains normal or slightly decreased
• Transaminases (AST/ALT): Remain within normal range 1

Laboratory Evaluation

• Complete blood count with platelets
• Comprehensive metabolic panel
• Coagulation studies (PT/INR, aPTT)
• Total serum bile acids (non-fasting preferred in pregnancy) 1, 2

Imaging

• Ultrasound: First-line and safest imaging modality at any gestational age
• MRCP: Safe at any gestational age if biliary obstruction is suspected
• Liver elastography: Safe but note that liver stiffness may increase slightly in third trimester
• Liver biopsy: Only when clinically necessary and delay in diagnosis would be dangerous 1

Diagnostic Algorithm Based on Trimester

First Trimester

1. Hyperemesis gravidarum (most common cause - 55.8%)

   • Characterized by intractable vomiting, dehydration
   • 40-50% have liver dysfunction, usually mild and self-limiting 1, 3
   • Management: Hydration, antiemetics, nutritional support

2. Viral hepatitis

   • Check hepatitis serologies (HAV, HBV, HCV, HEV)
   • Management depends on specific virus

3. Pre-existing liver disease

   • Autoimmune hepatitis, Wilson's disease, etc.

Second Trimester

1. Viral hepatitis (most common cause - 47%) 3

   • Management as per specific etiology

2. Intrahepatic cholestasis of pregnancy (ICP)

   • Characterized by pruritus and elevated bile acids
   • Check serum bile acids (non-fasting)
   • Management: Ursodeoxycholic acid, fetal monitoring 1, 2

3. Pre-existing liver disease

Third Trimester (Highest Risk)

1. HELLP syndrome (28.3% of third trimester cases) 3

   • Hemolysis, Elevated Liver enzymes, Low Platelets
   • Check blood pressure, urine protein, platelet count
   • Management: Delivery is definitive treatment 1, 2

2. Acute fatty liver of pregnancy (AFLP) (14.8% of third trimester cases) 3

   • Rare but potentially fatal (0.01% of pregnancies)
   • Presents with nausea, vomiting, abdominal pain, jaundice
   • Check coagulation, glucose, renal function
   • Management: Immediate delivery after stabilization 1, 2, 4

3. Preeclampsia

   • Most common cause of hepatic tenderness and liver dysfunction in late pregnancy
   • Check blood pressure, urine protein
   • Management: Antihypertensives, magnesium sulfate, delivery 2, 5

4. Intrahepatic cholestasis of pregnancy

   • Weekly monitoring of bile acids from 32 weeks
   • Early delivery if bile acids >100 μmol/L 1

Management Principles

For Intrahepatic Cholestasis of Pregnancy

• Ursodeoxycholic acid: First-line treatment for maternal pruritus and to reduce risk of spontaneous preterm birth 1
• Monitor bile acids weekly from 32 weeks' gestation
• Plan delivery at 35-37 weeks if bile acids >100 μmol/L due to increased stillbirth risk 1

For HELLP Syndrome

• Immediate delivery is the definitive treatment
• Magnesium sulfate for seizure prophylaxis
• Monitor for complications: DIC, hepatic rupture, renal failure
• Consider transfer to tertiary care center if severe 1, 6

For Acute Fatty Liver of Pregnancy

• Immediate delivery after maternal stabilization
• Intensive supportive care: Correct hypoglycemia, coagulopathy
• Consider ICU admission for encephalopathy, elevated lactate, or MELD score >30
• Early referral to transplant center if signs of liver failure present 1, 4

Special Considerations

Pre-existing Liver Disease

• Women with pre-existing cholestatic diseases should be advised:
  • 50% will have worsening or new pruritus during pregnancy
  • Most will have stable hepatic function during pregnancy
  • 70% have postnatal deterioration of liver tests
  • Higher risk of preterm birth and reduced live birth rates 1

Monitoring and Follow-up

• Any LFT abnormality during pregnancy is abnormal and requires investigation 2
• For mild, isolated elevations: Repeat LFTs in 2-4 weeks
• For persistent/worsening abnormalities: More frequent monitoring, consider hepatology referral
• Postpartum follow-up is essential to ensure resolution or diagnose underlying chronic disease
• Abnormalities persisting beyond 6 weeks postpartum warrant evaluation for chronic liver disease 2

Pitfalls to Avoid

1. Misinterpreting elevated ALP as liver disease - placental production causes physiologic elevation
2. Delaying delivery in AFLP or severe HELLP - immediate delivery is often life-saving
3. Overlooking non-alcoholic fatty liver disease - most common cause (51.3%) of liver dysfunction during pregnancy 7
4. Failing to monitor bile acids in ICP - levels >40 μmol/L increase risk of adverse outcomes
5. Missing the association between abnormal LFTs and preterm birth - abnormal AST, GGT, and bilirubin are independent risk factors for preterm birth 7

By following this algorithmic approach to deranged LFTs in pregnancy, clinicians can ensure timely diagnosis and appropriate management to optimize maternal and fetal outcomes.