Update on viral hepatitis in pregnancy
ABSTRACT
Pregnant women with acute viral hepatitis are at higher risk of morbidity and death than pregnant women with chronic viral hepatitis. The risk of death is highest with acute viral hepatitis E, and the rate of transmission to the baby may be highest with hepatitis B virus (HBV) infection. Managing viral hepatitis in pregnancy requires assessing the risk of transmission to the baby, determining the gestational age at the time of infection and the mother’s risk of decompensation, and understanding the side effects of antiviral drugs.
KEY POINTS
- Preventing vertical transmission of HBV infection in pregnancy is key to decreasing the global burden of this infection. Universal maternal screening and passive-active immunoprophylaxis of newborns have reduced transmission of HBV, but the addition of antiviral therapy is necessary to further decrease immunoprophylaxis failure.
- Tenofovir, telbivudine, and lamivudine can be used safely in pregnancy without apparent teratogenicity or other harmful effects on mother or baby. But optimal outcome requires discussion of safety and the plan of care with the patient, obstetrician, and hepatologist.
- Most pregnant women with hepatitis C virus (HCV) infection have chronic disease, with no effects on the pregnancy or baby, but 3% to 5% transmit HCV to their child at the time of birth. All pregnant women at risk should be screened at the first prenatal visit. The safety and efficacy of treating pregnant women to prevent transmission to the fetus are not established; thus, treatment is not recommended for pregnant women.
Risk of mother-to-child HBV transmission
Vertical HBV transmission can occur during the antepartum, intrapartum, and postpartum periods,18,19 but it most often occurs during the intrapartum period at the time of delivery. Without immunoprophylaxis of the newborn, the risk of mother-to-child transmission can be as high as 90% if the mother is hepatitis B e antigen-positive and has a viral load greater than 106 copies/mL. With active and passive immunoprophylaxis, the risk decreases substantially.
Screening and diagnosis
All pregnant women should be tested for hepatitis B surface antigen during the 1st trimester,20 or any time thereafter if early testing was not done, even if they were vaccinated before becoming pregnant.21
Prevention
HBV infection is best prevented before pregnancy by vaccinating the mother or, after delivery, by vaccinating the newborn. Universal vaccination of newborns has been the standard of care since the 1990s. Pregnant women should be tested early in the pregnancy; unvaccinated, uninfected women at high risk of acquiring HBV (eg, because of sexual contacts or intravenous drug use) should be vaccinated.2,3
HBV vaccine and immune globulin are both approved by the US Food and Drug Administration (FDA) for prevention of HBV infection and can be given during pregnancy and breastfeeding.3 All infants should be vaccinated for HBV at birth, and all infants born to mothers who test positive for hepatitis B s antigen should receive the HBV vaccine and the immune globulin within 12 to 24 hours after delivery. The vaccine series should be completed within 6 months.20,21 This will decrease the rate of neonatal infection.
Treatment of HBV infection in pregnancy
The main objectives of treating chronic HBV infection in pregnancy are to maintain stable liver function in the mother and to prevent neonatal infection, which may cause cirrhosis and hepatocellular carcinoma and contribute to the global burden of the disease.22 Therefore, maternal HBV DNA and liver aminotransferase levels should be tested regularly during gestation.
The current guidelines of the American Association for the Study of Liver Diseases suggest antiviral therapy to reduce the risk of perinatal transmission of HBV in pregnant women with an HBV DNA level greater than 200,000 IU/mL or greater than 106 copies/mL.23,24
In a meta-analysis,25 antiviral therapy with lamivudine, telbivudine, or tenofovir showed no apparent teratogenicity or safety concerns for maternal and fetal outcomes26 and significantly reduced the rate of mother-to-child transmission. Of these 3 drugs, telbivudine was associated with a higher rate of normalization of liver enzymes, HBV suppression, and e-antigen seroconversion.25 Lamivudine has proven the test of time in mothers co-infected with HBV and human immunodeficiency virus (HIV). However, tenofovir is considered the preferred treatment in pregnancy, owing to concerns about drug resistance to telbivudine and lamivudine and a high genetic barrier to resistance with tenofovir.26 In mothers with HBV and HIV treated with tenofovir, treatment was associated with lower bone mineral density in the newborns, with a propensity for renal injury in the mothers. No safety concerns for maternal or fetal outcomes were identified in pregnant women infected only with HBV.25
Many pregnant mothers choose to stop therapy around the time of conception because of safety concerns for the baby. In such situations, close monitoring is necessary to detect flares of HBV infection.
When the decision to treat is made, treatment should begin at 28 to 30 weeks of gestation, when organogenesis is complete and to allow enough time for HBV DNA levels to decline.
Breastfeeding is not contraindicated because antiviral drugs are minimally excreted in breast milk and are unlikely to cause toxicity. However, data are insufficient as to the long-term safety for the newborn when the mother took these drugs during pregancy and while breastfeeding.23,27
Alanine aminotransferase and HBV DNA levels should be monitored postpartum because of the possibility of a hepatitis flare. In this setting, any of the three drugs can be used.28 For mothers on therapy because of cirrhosis or an advanced histologic feature, antiviral therapy should be continued throughout pregnancy to prevent disease progression and decompensation.19,22,27
No drug therapy is necessary for pregnant carriers of HBV.
