What is the appropriate management for a pregnant woman in her 2nd trimester with chronic Hepatitis B infection, positive HBsAg and HBe antigen, high HBV DNA levels, and impaired liver function?

Management of Chronic Hepatitis B in Second Trimester Pregnancy with Elevated Liver Enzymes

This patient requires immediate initiation of tenofovir disoproxil fumarate (TDF) 300 mg daily, given her high viral load (HBV DNA 10^5 IU/mL), positive HBeAg status, and significantly elevated transaminases indicating active hepatitis with potential for liver failure. 1, 2

Immediate Management Priorities

Antiviral Therapy Initiation

• Start TDF 300 mg orally daily immediately - do not wait until 24-28 weeks given the markedly elevated transaminases (ALT 1210 U/L, AST 673 U/L) and total bilirubin of 6.3 mg/dL, which indicate acute-on-chronic liver injury requiring urgent treatment 1, 2
• TDF is the only recommended antiviral agent in pregnancy due to superior safety data, high genetic barrier to resistance, and proven efficacy 1, 3
• Continue TDF throughout pregnancy and until 2-12 weeks postpartum 1, 4

Critical distinction: While guidelines typically recommend starting TDF at 24-32 weeks for viral suppression alone, this patient has advanced liver disease with severe hepatitis requiring immediate treatment to prevent maternal liver failure and death 1

Autoimmune Hepatitis Workup

• Obtain antinuclear antibody (ANA), anti-smooth muscle antibody (ASMA), anti-liver kidney microsomal antibody (anti-LKM), and serum immunoglobulin G levels 1
• The markedly elevated transaminases with hyperbilirubinemia raise concern for concurrent autoimmune hepatitis or acute hepatitis flare
• However, do not delay TDF initiation while awaiting autoimmune workup results 1

Monitoring for Liver Failure

• Assess prothrombin time/INR and albumin immediately to evaluate synthetic liver function 1
• Monitor for signs of hepatic encephalopathy, coagulopathy, and ascites 1
• Consider hepatology consultation given severity of liver injury 1

Rationale for Immediate TDF Treatment

Dual Indications Present

1. Prevention of vertical transmission: HBV DNA >200,000 IU/mL (10^5 = 100,000 IU/mL meets threshold) with positive HBeAg creates high risk of immunoprophylaxis failure in the infant 1, 2, 4
2. Treatment of maternal liver disease: The severely elevated transaminases and bilirubin indicate active hepatitis requiring treatment to prevent progression to liver failure 1

Safety Profile

• TDF has extensive safety data in pregnancy with no increased risk of congenital abnormalities (2.1% vs 2.7% background rate) 3, 5
• Published studies of 327 pregnant women receiving TDF from 28-32 weeks showed no new safety concerns 3
• Studies using TDF throughout pregnancy (not just third trimester) demonstrate excellent safety and efficacy 5

Vertical Transmission Prevention Strategy

Neonatal Management Plan

• Infant must receive both hepatitis B vaccine AND hepatitis B immune globulin (HBIG) within 12 hours of birth 2, 4
• Complete standard vaccine series at 1,2, and 6 months 4
• Test infant for HBsAg and anti-HBs at 9-12 months of age 1, 4

Expected Efficacy

• TDF reduces mother-to-child transmission to 0% in most studies when combined with neonatal immunoprophylaxis 1, 5, 6
• Without TDF, transmission rates range from 6-13% despite immunoprophylaxis in high viral load mothers 5, 7, 6

Delivery and Postpartum Management

Mode of Delivery

• Vaginal delivery is recommended - cesarean section should not be performed solely for HBV transmission prevention 2, 4
• Standard obstetric indications should guide delivery mode 2

Breastfeeding

• Breastfeeding is safe and encouraged, even while on TDF therapy 1, 2, 8
• Tenofovir concentrations in breast milk are minimal and oral bioavailability is limited 1, 8
• The European Association for the Study of the Liver states with 100% consensus that breastfeeding should not be discouraged 8

Postpartum Monitoring

• Critical monitoring period: Check ALT and HBV DNA every 4-12 weeks for 6 months after stopping TDF 1, 4
• Risk of hepatitis flare is highest in the postpartum period due to immune reconstitution 1, 9
• In this patient with pre-existing severe hepatitis, strongly consider continuing TDF long-term rather than stopping postpartum 1

Common Pitfalls to Avoid

Do Not Delay Treatment

• The severely elevated transaminases and bilirubin indicate this patient needs immediate treatment, not delayed initiation at 24-28 weeks 1
• Waiting could result in maternal liver failure, fetal loss, or maternal death 1

Do Not Use Alternative Antivirals

• Lamivudine and telbivudine have inferior resistance profiles and less safety data 1, 2
• Entecavir has inadequate pregnancy safety data and should be switched to TDF if patient becomes pregnant 1, 2
• Pegylated interferon is absolutely contraindicated in pregnancy 1

Do Not Discourage Breastfeeding

• Outdated guidance suggested avoiding breastfeeding, but current evidence strongly supports safety with proper infant immunoprophylaxis 1, 2, 8

Do Not Stop TDF Abruptly Postpartum

• This patient's severe hepatitis suggests underlying advanced liver disease requiring long-term treatment 1
• Abrupt cessation can precipitate severe hepatitis flares 1, 9
• Reassess treatment indications postpartum rather than automatically discontinuing 1

Long-Term Considerations

Given the severity of this patient's liver disease (markedly elevated transaminases, hyperbilirubinemia, positive HBeAg, high viral load), she likely has advanced fibrosis or cirrhosis and will require lifelong antiviral therapy beyond pregnancy 1. The pregnancy provides an opportunity to initiate appropriate treatment that should continue indefinitely 1.