What are the causes and management of transaminitis (elevated liver enzymes) in pregnancy?

Causes of Transaminitis in Pregnancy

The most common causes of transaminitis in pregnancy include intrahepatic cholestasis of pregnancy (ICP), preeclampsia with HELLP syndrome (Hemolysis, Elevated Liver enzymes, Low Platelets), and acute fatty liver of pregnancy (AFLP), which require prompt diagnosis and management to reduce maternal and fetal morbidity and mortality. 1

Pregnancy-Specific Causes of Transaminitis

Intrahepatic Cholestasis of Pregnancy (ICP)

• Characterized by pruritus (typically on palms and soles) and elevated bile acids
• Usually presents in the second or third trimester
• Laboratory findings:
  • Elevated total serum bile acids (>10 μmol/L is diagnostic) 1
  • Transaminase elevations (ALT/AST) may be mild to moderate
  • Bilirubin usually normal or mildly elevated

Preeclampsia and HELLP Syndrome

• Presents with hypertension, proteinuria, and elevated liver enzymes
• HELLP syndrome includes:
  • Hemolysis (abnormal peripheral blood smear)
  • Elevated liver enzymes (ALT/AST)
  • Low platelets (<100,000/μL)
• Typically occurs after 20 weeks gestation
• May present with right upper quadrant pain

Acute Fatty Liver of Pregnancy (AFLP)

• Rare but life-threatening condition
• Usually presents in third trimester
• Clinical features include:
  • Nausea, vomiting, abdominal pain
  • Jaundice
  • Markedly elevated transaminases
  • Hypoglycemia
  • Coagulopathy
  • Encephalopathy in severe cases

Non-Pregnancy Specific Causes

Viral Hepatitis

• Hepatitis A, B, C, E (particularly HEV in pregnancy)
• Epstein-Barr virus, cytomegalovirus
• Presents with malaise, fatigue, jaundice
• Marked elevation of transaminases (often >1000 IU/L) 2

Drug-Induced Liver Injury

• Medications (antibiotics, antiepileptics, statins) 3
• Herbal supplements
• Variable pattern of liver injury (hepatocellular, cholestatic, or mixed)

Autoimmune Hepatitis (AIH)

• May present for first time or flare during pregnancy
• Associated with other autoimmune conditions
• Elevated immunoglobulins, positive autoantibodies (ANA, SMA)
• May require immunosuppressive therapy during pregnancy 1

Biliary Disorders

• Cholelithiasis and cholecystitis (more common in pregnancy)
• Primary biliary cholangitis (PBC)
• Primary sclerosing cholangitis (PSC)
• Can present with right upper quadrant pain and elevated alkaline phosphatase 4

Other Causes

• Nonalcoholic fatty liver disease (NAFLD) - most common cause of transaminitis in general population 5
• Alcoholic liver disease
• Ischemic hepatitis (shock liver) - most common cause of marked transaminase elevation (>1000 IU/L) 2
• Hereditary liver diseases (Wilson's disease, hemochromatosis, α1-antitrypsin deficiency)

Diagnostic Approach

1. Initial laboratory evaluation:

   • Complete blood count with platelets
   • Comprehensive metabolic panel
   • Coagulation studies (PT/INR)
   • Total serum bile acids
   • Hepatitis serologies (A, B, C)
   • Autoimmune markers if suspected

2. Imaging:

   • Ultrasound is first-line and safest in pregnancy
   • MRI without contrast if further evaluation needed
   • MRCP for suspected biliary obstruction

3. Specialized testing based on clinical suspicion:

   • Viral PCR studies
   • Iron studies
   • Ceruloplasmin (Wilson's disease)
   • α1-antitrypsin level

Management Principles

For ICP:

• Ursodeoxycholic acid (UDCA) should be offered for:
  • Relief of maternal pruritus
  • Reduction of spontaneous preterm birth risk
  • Possible protection against stillbirth 1
• Weekly monitoring of total serum bile acids from 32 weeks
• Consider delivery at 35 weeks if bile acids >100 μmol/L due to increased stillbirth risk
• For bile acids <100 μmol/L, consider delivery by 39 weeks 1

For HELLP Syndrome:

• Prompt delivery is often necessary
• Magnesium sulfate for seizure prophylaxis
• Antihypertensive therapy for severe hypertension
• Close monitoring of maternal and fetal status

For AFLP:

• Immediate delivery after maternal stabilization
• Intensive supportive care
• Correction of hypoglycemia, coagulopathy
• May require plasma exchange in severe cases

For Autoimmune Hepatitis:

• Continue immunosuppressive therapy (prednisolone, azathioprine) throughout pregnancy
• Monitor for postpartum flares
• Close obstetric surveillance for complications 1

Key Pitfalls to Avoid

1. Delayed diagnosis of pregnancy-specific liver diseases, which can lead to increased maternal and fetal morbidity and mortality
2. Attributing all liver enzyme elevations to pregnancy without considering non-pregnancy related causes
3. Failure to monitor bile acid levels in ICP, which correlate with fetal risk
4. Inadequate postpartum follow-up - liver enzymes should normalize within 3 months; persistent abnormalities warrant investigation for underlying liver disease

Special Considerations

• All women with transaminitis in pregnancy should be managed by a multidisciplinary team including obstetricians and hepatologists
• Liver biopsy is rarely indicated during pregnancy and should be reserved for cases where the diagnosis remains unclear and management would be altered
• Postpartum follow-up is essential to ensure resolution of pregnancy-related liver diseases or to diagnose underlying chronic liver disease

Remember that prompt diagnosis and appropriate management of the underlying cause of transaminitis in pregnancy is crucial to optimize both maternal and fetal outcomes.