Management of HBV infection in pregnancy: 2022 APASL guidelines released!

Guide

In February 2022, the Asia Pacific Society for Liver Research (APASL) published guidelines for the management of hepatitis B virus (HBV) infection in pregnancy. HBV infection remains a major public health problem in the Asia-Pacific region, where the bulk of the burden of HBV-related diseases comes from infants becoming infected through perinatal exposure. This article provides guidance on the management of HBV infection during pregnancy.

2022 APASL Guidelines: Management of HBV Infection in Pregnancy

How does HBV infection (acute and chronic) affect the health and pregnancy outcomes of pregnant women?

HBV infection during pregnancy does affect perinatal and pregnancy-related outcomes in both mother and newborn. Maternal effects include miscarriage, gestational diabetes, gestational hypertension, preterm birth, intrahepatic cholestasis during pregnancy, and caesarean section. However, available research data are insufficient to correlate these complications with isolated HBV infection (B2).

Effects of pregnancy on the severity and outcome of HBV infection (acute and chronic) in HBV-infected pregnant women and on the management of liver disease (general management and use of antiviral drugs).

Acute hepatitis B infection in pregnant patients usually requires specialized supportive care (weak recommendation, medium-quality evidence); if the condition is severe and progressive, emergency liver transplantation may be required. In rare cases, early termination of pregnancy and early fetal delivery are required (B2).

For women who have received nucleoside (acid) analogue (NA) prior to pregnancy and have been diagnosed with advanced fibrosis/cirrhosis, continuing NA therapy throughout pregnancy (B1) is highly recommended.

Women who have received NA before pregnancy and have mild levels of fibrosis should be considered for continuing NA therapy during pregnancy (C1).

During pregnancy, medication should be considered from class C to class B of the FDA's classification of pregnancy drugs. Tenofovir ester (TDF) is recommended as the antiviral agent of choice for pregnant women (B1).

For chronic HBV-infected women who are not eligible for antiviral therapy and therefore are not treated at the time of pregnancy, HBV DNA and alanine aminotransferase (ALT) levels must be monitored throughout pregnancy until 6 months after pregnancy, and treatment is required if severe acute elevation of ALT is confirmed (B1).

Pregnant women with chronic HBV infection and confirmed cirrhosis and pregnancy plans should be endoscopicly monitored for varicose veins. Prophylactic varicose vein management (C1) before pregnancy is recommended.

For pregnant women with cirrhosis, endoscopic monitoring in the second trimester of pregnancy and treatment of medium and large varicose veins (C1) is recommended even if varicose veins are not detected in pre-pregnancy screening.

Mechanisms of mother-to-child transmission (MTCT) of HBV and related risk factors

MTCT of HBV occurs mainly during childbirth. The rate and timing of intrauterine transmission is unknown and requires further study (B2).

Known risk factors for MTCT are high maternal HBV DNA levels or positive hepatitis B e antigen (HBeAg), as well as poor use of hepatitis B immunoglobulin (HBIG) and/or hepatitis B vaccine after birth (A1).

Prevention of MTCT

All newborns should receive the first dose of hepatitis B vaccine as soon as possible after birth, preferably within 24 h, and then 3 doses after birth to complete the basic immunization (A1).

HBIG prophylaxis combined with HBV vaccination may have additional benefits for maternal hepatitis B surface antigen (HBsAg) positive and HBeAg-positive newborns. For term newborns born to HBsAg-positive but HBeAg-negative mothers, the protective effect against perinatal acquired infection achieved through immediate vaccination of HBV vaccine (within 24 hours) may not be significantly enhanced by the addition of HBIG (B1).

Pregnant women with HBsAg-positive HBV DNA ≥ 5.3 log10 IU/mL (≥200,000 IU/mL) should receive antiviral prophylaxis to prevent MTCT of HBV. This is a supplement to appropriate immunoprotective (B1).

In cases where prenatal HBV DNA testing is not possible, HBeAg testing can be used as an alternative to HBV DNA testing to determine whether tenofovir is appropriate for MTCT (B2) to prevent HBV.

TDF is recommended for pregnant women with HBV who require antiviral prophylaxis to prevent MTCT (B1) of HBV.

Antiviral therapy should be started at 24 to 28 weeks' gestation to prevent MTCT. For pregnant women with hyperviralemia who come to the hospital after 28 weeks of pregnancy, antiviral interventions should be started immediately. Even if HBV DNA levels are low, pregnant women should be made aware of the risk of intrauterine transmission of HBV and may choose to start antiviral therapy (C2) from the first trimester of pregnancy.

Pregnant women who are prevented with antiviral drugs against MTCT may stop antiviral therapy immediately after delivery or continue until 12 weeks postpartum (C2) and should be closely monitored for hepatitis outbreaks and HBV DNA rebound for at least 24 weeks (C2).

Pregnant women with acute elevation of ALT during pregnancy or evidence of advanced liver fibrosis or cirrhosis should continue long-term antiviral therapy after delivery and should follow the discontinuation rules (C1) of the guidelines for patients with chronic hepatitis B (CHB).

Postpartum follow-up (C1) should be performed at least 24 weeks after discontinuation of antiviral drugs (for MTCT only).

Safety of invasive surgery in HBV-infected pregnant women in terms of MTCT and the best way to give birth for HBsAg-positive mothers

Pregnant women and their relatives should discuss the risk of intrauterine HBV transmission in pregnant women with high serum HBV DNA levels (≥7 log10 IU/mL) and planning invasive procedures (e.g., amniocentesis). The pros and cons need to be weighed (C2).

Caesarean section should not be used as the only indication to reduce the risk of vertical transmission of HBV (C1).

Chronic HBV infection and assisted conception

Assisted reproduction (C2) can be performed in the same guidelines as other pregnant women with chronic HBV infection.

Postpartum follow-up of children of mothers with chronic HBV infection

All children born to HBsAg-positive mothers should have a seroconversion test (HBsAg and anti-HBs titer) at 9-18 months and at least 1 month after the last dose of vaccination (B1).

Breastfeeding in HBV-infected mothers

Mothers should be encouraged to breastfeed, as there are no cracks, bleeding or lesions in the nipple after proper immunoprophylaxis in the infant and breastfeeding does not result in MTCT (B1) of HBV.

Breastfeeding should not be prohibited for mothers receiving tenofovir for the prevention or treatment of HBV, and breastfeeding should be encouraged for mothers receiving TDF treatment (B1).

Public health aspects of HBV infection during pregnancy

All pregnant women should be screened for HBsAg as early as possible during pregnancy. Screening should be performed in every pregnancy, regardless of whether previous HBV vaccine has been given or previous HBsAg test results have been negative (C1).

HBsAg screening of pregnant women should include counseling before and after testing, as well as further treatment as appropriate (C1).

Timely expansion of vaccination rates is the most cost-effective option for preventing MTCT. Countries that have not yet met the 2020 target of 1% prevalence of HBsAg in children under 5 years of age through vaccination should focus on increasing their vaccination coverage, including timely vaccination (A1).

Countries that have expanded vaccination rates in a timely manner, increasing prenatal HBsAg testing for pregnant women and tenofovir prophylaxis for eligible women to prevent MTCT may be cost-effective in some settings (B1).