What are the treatment guidelines for autoimmune hepatitis in pregnancy?

Treatment of Autoimmune Hepatitis in Pregnancy

Continue immunosuppressive therapy throughout pregnancy with prednisolone (prednisone) as the preferred agent, with azathioprine continuation being acceptable and likely beneficial for maintaining disease control, as discontinuation significantly increases the risk of disease flares that pose greater maternal and fetal risks than the medications themselves. 1

Medication Management During Pregnancy

Corticosteroids (Preferred Agent)

• Prednisolone/prednisone should be continued or initiated during pregnancy at doses sufficient to maintain disease remission, typically 5-20 mg daily 1
• Corticosteroids alone can effectively induce and maintain remission with equivalent efficacy to combination therapy 1
• Prednisolone is considered safe during pregnancy and is the first-line agent when treatment adjustments are needed 1, 2

Azathioprine (Acceptable to Continue)

• Despite FDA Category D classification, continuation of azathioprine during pregnancy is justified and recommended by European guidelines based on substantial safety data 1
• Large observational studies show no apparent relationship between azathioprine use and adverse fetal outcomes: in 81 pregnancies at King's College Hospital, 75% of patients received pharmacotherapy (including azathioprine), with a 73% live birth rate and no increase in congenital abnormalities beyond baseline population rates 1
• The 2015 EASL guidelines explicitly state that "continuation of this drug during pregnancy appears to be justified" based on pooled data showing no significant increase in congenital abnormalities (OR 1.45,95% CI 0.99-2.13) 1
• Flares are more likely in patients without therapy or who discontinue treatment, making medication continuation critical for maternal safety 1

Contraindicated Medications

• Mycophenolate mofetil (MMF) is absolutely contraindicated in pregnancy and must be discontinued prior to conception 1

Disease Behavior During Pregnancy

Pregnancy Course

• Disease activity is unpredictable: flares occur in 21-33% of pregnancies, while some patients experience stabilization or even improvement 1
• The postpartum period carries the highest risk for disease flares (52% in one series), requiring intensified monitoring 1
• Serious maternal complications (death, transplant need, or hepatic decompensation) occur in approximately 11% of pregnancies, significantly higher in women with established cirrhosis 1

Risk Factors for Adverse Outcomes

• Cirrhosis at conception increases risk of lower live birth rates, prematurity, and maternal decompensation 1
• Patients without therapy or with disease flares in the year prior to conception face higher flare risk during pregnancy 1
• Women with advanced liver disease and portal hypertension are at risk for variceal hemorrhage and should receive contraceptive counseling 1

Monitoring Protocol

During Pregnancy

• Continue standard immunosuppressive regimen with minimal adjustments 1
• Monitor liver enzymes (AST/ALT), bilirubin, and immunoglobulin levels regularly throughout pregnancy 1
• Maintain disease remission as the primary goal to prevent maternal decompensation 1

Peripartum Management

• Resume or intensify standard therapy 2 weeks before anticipated delivery to prevent postpartum flares 1
• Monitor serum AST/ALT levels at 3-week intervals for at least 3 months postpartum, as this is the highest-risk period for disease reactivation 1
• Maintain heightened surveillance for 3-12 months after delivery 1

Fetal and Neonatal Outcomes

Expected Outcomes

• Live birth rate of approximately 73% in treated patients 1
• Prematurity occurs in 11-20% of pregnancies 1, 3
• Congenital malformation rates are not significantly elevated above baseline population rates when azathioprine is used 1, 4
• Cesarean section rates may be higher (23-25%) 1, 5

Breastfeeding Considerations

• Azathioprine and 6-mercaptopurine are considered safe for breastfeeding despite small amounts of metabolites detectable in breast milk, as these do not appear to cause infant complications 1
• Prednisolone is compatible with breastfeeding 1

Critical Clinical Pitfalls

The most dangerous error is discontinuing immunosuppression during pregnancy based on outdated concerns about azathioprine teratogenicity. The evidence clearly demonstrates that:

• Disease flares pose greater maternal and fetal risks than continued medication 1
• Maternal hepatic decompensation significantly worsens fetal outcomes 1
• Retrospective data from multiple large series support azathioprine safety 1, 4

The second major pitfall is inadequate postpartum monitoring, as over half of disease flares occur in the 3 months following delivery when surveillance may inadvertently decrease 1

Divergent Guideline Recommendations

There is a notable difference between American and European guidelines regarding azathioprine:

• 2010 AASLD guidelines recommend discontinuing azathioprine "if possible" during pregnancy based on FDA Category D status 1
• 2015 EASL guidelines recommend continuation of azathioprine based on accumulated safety data showing no apparent relationship with adverse outcomes 1

The more recent EASL position (2015) should guide practice, as it incorporates larger observational datasets demonstrating that the theoretical risks of azathioprine are outweighed by the documented risks of disease flares from treatment discontinuation 1. The British Society of Gastroenterology similarly recommends "minimal adjustment" of immunosuppressive regimens 1.