The combination of chronic hepatitis B (CHB) in pregnancy is an important issue that is both common and uniquely challenging. HBV infection in pregnant women is different from the general population and requires thinking about a number of special issues: such as the impact of HBV infection on the mother and fetus, the effect of pregnancy on HBV replication, whether HBV antiviral therapy should be administered during pregnancy, the impact of these treatments on the mother and fetus, how newborns are immunized, and whether hepatitis activity can be induced postpartum. This article provides a review of the management of pregnant CHB patients from clinical practice.
Combined chronic hepatitis B (CHB) in pregnancy is an important issue that is both common and uniquely challenging. HBV infection in pregnant women is different from the general population and requires thinking about a number of special issues: such as the impact of HBV infection on the mother and fetus, the effect of pregnancy on HBV replication, whether HBV antiviral therapy should be administered during pregnancy, the impact of these treatments on the mother and fetus, how newborns are immunized, and whether hepatitis activity can be induced postpartum. This article provides a review of the management of pregnant CHB patients from a clinical practice perspective.
Interaction of pregnancy and chronic hepatitis B
During pregnancy, a series of physiological changes occur in the mother, such as high maternal metabolism and high nutrient consumption; during pregnancy, the mother produces a large amount of sex hormones that need to be metabolized and inactivated in the liver, and the fetus also relies on the maternal liver for metabolism and detoxification. HBV infection can increase the burden of existing liver disease and worsen liver damage. There is a tendency for ALT to increase in late pregnancy and postpartum, but there is no significant difference in HBV replication during pregnancy. A proportion of women experience immune activation for HBeAg seroconversion in the initial months after delivery, and studies have found a seroconversion rate of 12.5% to 17% during this period, which may be related to the marked decline in adrenocorticotropic hormones after delivery.
Overall, chronic HBV infection in women of childbearing age has no serious impact on the course of pregnancy. Some studies have reported that chronic HBV infection is associated with gestational diabetes, antepartum hemorrhage, preterm delivery, and reduced fetal Apgar score. If the mother has severe liver function abnormalities, she is prone to postpartum hemorrhage, increased chances of puerperal infection, low fetal weight, fetal distress, preterm delivery, stillbirth, and neonatal asphyxia.
Although HBV infection is often tolerated during pregnancy, there are still perinatal hepatitis outbreaks leading to severe hepatic failure and poor prognosis for mother and child.
Perinatal management of patients with chronic hepatitis B
Perinatal screening for HBV has become an integral part of standard perinatal care due to the availability of relatively safe and effective treatment options for HBV. Screening for maternal HBV infection identifies newborns who require primary-passive immunization with hepatitis B vaccine and hepatitis B immune globulin (HBIG) and pregnant women who require antiviral medication during pregnancy, and allows for guidance on sexual and family contact for HBV-infected patients.
HBV-infected women should do plan their pregnancies. Baseline assessment is recommended prior to pregnancy: HBsAg, HBeAg, anti-HBe, HBV DNA, severity of liver disease, and whether other viral infections are co-infected. Assess their tolerance for pregnancy and the risk of mother-to-child transmission. All pregnant women must be screened for HBV at the first antenatal visit during early pregnancy; all those screened positive for HBsAg should be referred to a hospital with experience in managing pregnant women with hepatitis B. This will facilitate monitoring of the mother during pregnancy, delivery, postpartum, and the newborn, as well as access to appropriate mother-to-child blockade treatment on an individual basis.
Treatment of chronic HBV infection in pregnancy
The goals of treatment for CHB in pregnancy are: stable liver function during maternal pregnancy and no HBV infection in the newborn. regular monitoring of liver function and HBV DNA levels throughout maternal pregnancy is required to assess whether maternal liver disease has progressed and whether antiviral therapy is needed.
① If the baseline HBV DNA level is low (HBV DNA < 106 copies/mL for HBeAg positive; HBV DNA < 105 copies/mL for HBeAg negative) and there is no significant fibrosis, antiviral therapy will be withheld and monitoring will be performed during pregnancy. If HBV DNA >107 copies/mL or HBV DNA >106 copies/mL is repeatedly tested in the third trimester of pregnancy and there is a history of previous births of HBV-positive infants, antiviral therapy should be given; otherwise, antiviral therapy can be withheld.
② If the baseline HBV DNA level is high and there is significant liver fibrosis but no cirrhosis, antiviral therapy is recommended first. If the response can be sustained after drug discontinuation, pregnancy can be carried out and monitored during pregnancy and treated as ①; if the response cannot be maintained after drug discontinuation, the treatment will be the same as ③.
(iii) If cirrhosis existed before pregnancy, it is recommended to start antiviral therapy before pregnancy and choose lamivudine (LAM) or tenofovir (TDF) or telbivudine (LdT), and continue antiviral therapy with one of the above drugs during pregnancy, and monitor throughout pregnancy.
Issues related to antiviral therapy in pregnancy
Intrauterine and perinatal transmission of HBV is clearly correlated with maternal HBV DNA levels, and high levels of HBV DNA are an independent risk factor for the occurrence of intrauterine transmission. The most studied method of blocking mother-to-child transmission is the treatment of pregnant women with oral antiviral drugs in late pregnancy, which reduces HBV transmission from mother to child by lowering the titer of HBV DNA in the peripheral blood of pregnant women before delivery.
(1) Selection of antiviral drugs. Interferon has proliferation-inhibiting effects and is prohibited for use during pregnancy, and those who apply it should stop using it for six months before pregnancy. To date, the FDA certified antiviral drugs for pregnancy class B are LdT and TDF. In view of the increasing safety data of LAM in clinical application, the National Institutes of Health (NIH) upgraded LAM to pregnancy class B drugs.
② Indications for antiviral therapy. All pregnant women who screen positive for HBsAg are recommended for baseline evaluation during early pregnancy for: HBsAg, HBeAg, anti-HBe, HBV DNA, hepatitis activity, liver fibrosis, or degree of cirrhosis. If HBV DNA levels are high and hepatitis activity (ALT > 2 x ULN, HBV DNA > 105 copies/mL) or cirrhosis is present in early pregnancy, antiviral therapy is administered in early pregnancy. For pregnant women with normal liver function, ALT and HBV DNA should be re-evaluated at mid-pregnancy (26-28 weeks); those with HBV DNA >107 copies/mL or HBV DNA >106 copies/mL and a history of previous delivery of HBV-positive infants should be given LAM, TDF or LdT antiviral therapy at 28-30 weeks and continue until 4 weeks postpartum. The decision to continue is based on the condition; otherwise, antiviral therapy may be withheld. If cirrhosis existed before pregnancy, it is recommended to administer antiviral treatment before pregnancy and choose LAM, TDF or LdT, and continue antiviral treatment with one of the above drugs during pregnancy, and monitor throughout pregnancy.
(iii) Women who become pregnant unintentionally during anti-HBV treatment need to be managed individually for each case. There are two options: one is to temporarily discontinue the drug, monitor HBV DNA and ALT levels throughout the pregnancy, and then decide whether to give antiviral therapy according to the specific situation in the second trimester, which is suitable for patients with mild hepatitis and less risk of severe rebound or disease progression; the other is to continue antiviral therapy throughout the pregnancy, but should be changed to LAM, TDF or LdT. neonates require combined primary-passive immunization and breastfeeding does not increase the risk of HBV infection in neonates, evidence of the safety of these drugs in neonates exposed during breastfeeding has not been obtained for pregnant women who have received antiviral therapy whether or not to breastfeed.
Management of HBV-infected pregnant women during and after delivery
The mode of delivery to interrupt HBV infection in infants has also been considered a potential risk factor for the occurrence of mother-to-child transmission. However, to date, there is no reliable evidence-based medical evidence to confirm the impact of mode of delivery on reducing mother-to-child transmission of HBV.
All newborns of HBsAg-positive mothers should be immunized with combined primary-passive immunization on schedule after birth, and blood should be drawn for infant HBsAg, HBeAg, anti-HBe, and HBV DNA at birth and at 7 months of age. hepatitis B vaccination and combined HBIG immediately after birth are effective in blocking infection during delivery and postpartum infection, but not for intrauterine infection that has already occurred. This is the main cause of immunization failure in infants after birth.
All HBsAg-positive pregnant women should be monitored for ALT and HBV DNA at 1, 3, and 6 months postpartum, and observed for serologic conversion and anti-HBe positive conversion if hepatitis activity is present.
In summary, perinatal transmission of HBV is a major cause of chronic HBV infection, and to reduce the burden of HBV it is necessary to consider how to interrupt this mode of transmission. Specific testing, interventions and follow-up measures for this special population of chronically HBV-infected women of childbearing age deserve particular attention and exploration.