The issue of fertility and antiviral treatment in chronic HBV-infected patients during pregnancy or childbearing age has been a practical problem that has plagued patients as well as clinicians. There is no unanimity of opinion on this issue in China and abroad, but there is some evidence-based medicine in the American Liver Congress, the Asia-Pacific Liver Congress, and some studies. In clinical practice, the largest number of patients ask such questions, so for the sake of the general public to have access to new information, I will outline two issues here.
I. Summary of findings from studies on pregnancy and HBV infection.
(i) Prevalence of infection in newborns born to HBV-infected mothers.
The rate of HBV infection in newborns who do not receive formal immunoprophylaxis after birth is 70% to 90%, with the rate of infection in newborns of women with HBeAg(+) significantly higher than that of women with HBeAg(-). The protection rate against HBV infection in newborns who receive standardized immunoprophylaxis immediately after birth can reach more than 90%.
(ii) About how mother-to-child transmission of HBV occurs?
Some studies have shown that mother-to-child transmission of HBV occurs mainly in the perinatal period (28th week of gestation to 7 days postpartum), and the mother-to-child transmission rates of newborns born to pregnant women with HBeAg(+) and HBeAg(-) mothers are 85% and 31%, respectively.
1. The transmission routes can be divided into three types of transmission: prenatal, at delivery and postnatal horizontal transmission. We will then we divide the pregnancy into three phases.
Phase I: 0-12 weeks of gestation; Phase II, 13-27 weeks of gestation; Phase III: 28-40 weeks of gestation. Whereas 85% of neonatal HBV infections are due to exposure of the mother’s blood and vaginal fluids to the infant during delivery, that is, in the third trimester, the second is intrauterine infection (prenatal), which has a transmission rate of less than 5%. HBV can be detected in the breast milk of infected mothers, and horizontal transmission can occur after birth if breastfeeding is used and the mother-to-child blockade of the newborn fails, due to damage to the oral mucosa of the newborn! However, if the newborn has undergone standardized immunization and has achieved the desired effect (the newborn has produced HBsAb,) breastfeeding can be considered.
2. High risk factors for mother-to-child transmission are mainly related to the viral load of HBV-DNA in pregnant women.
If the mother’s serum HBV-DNA level is <107IU/ml (≈5×107copies/ml), the success rate of immunoprophylaxis for her newborn is 100%; if the mother's serum HBV-DNA level is >107IU/ml, the success rate is only 68%. It has also been shown that reducing serum HBV-DNA to <106copis/mL in mothers with HBV infection who do not receive vaccine prophylaxis (e.g., by taking lamivudine) can reduce HBV infection in newborns from 78.8% to 44.4%, a decrease of up to 30%.
(iii) What is the formal neonatal immunoprophylaxis strategy?
Our immunoprophylaxis strategy is to give 100 IU of HBIG (specific hepatitis B immunoglobulin) to newborns born to HBsAg(+) mothers within 12 hours of birth, along with 10ug of recombinant yeast vaccine at different sites, followed by 10ug of vaccine once at 1 month and once at 6 months after birth.
For mothers who are HBsAg-positive, either major or minor triplets, the above method is used for the planned immunization of newborns, while for fathers who are HBsAg-positive and mothers who are HBsAg-negative (or HBsAb-antibody-positive), only hepatitis B vaccine can be given to newborns.
For HBsAg(-) mothers, 5ug of recombinant yeast vaccine is sufficient. Some scholars have conducted controlled studies showing that: for HBsAg(+) mothers, the protection rate of single vaccination is 72%; the protection rate of active+passive immunization with vaccine combined with HBIG (i.e., hepatitis B vaccination) is 95%; and only a very small percentage of 5% of newborns without prophylaxis are not infected with HBV.
Second, the choice of antiviral drugs to interrupt mother-to-child transmission.
1, recently prepared for pregnancy, general antiviral, try to choose alpha interferon preparations, because it has a fixed course of treatment, at least 48 weeks, can be extended to 1.5 years, the course of treatment to 1.5 years, if the HBsAg titer has decreased, you can insist on another six months, in order to achieve the desired treatment goal – the negative surface antigen, or even the appearance of surface antibodies. However, fewer patients can achieve this goal.
2. Nucleoside analogues available – lamivudine and telbivudine
Classification of nucleoside (acid) analogues in pregnancy: lamivudine, telbivudine, emtricitabine and tenofovir are classified in category B. These drugs can be applied if the benefits of their application for the mother and fetus outweigh the risks. Entecavir and adefovir, which have been shown to have embryonic and fetal toxicity in animal studies, are classified as Category C. Plain interferon and pegylated interferon are contraindicated during pregnancy due to their antiproliferative effects (both refer to pregnant women).
The advantages of lamivudine are that it is the longest used and most experienced of the nucleoside (acid) analogs and the safest; there is a large body of evidence-based medicine for use in pregnant women. In particular, it has accumulated a great deal of successful experience in its use to block mother-to-child transmission of HIV (AIDS) (at anti-HIV, patients take 300 mg of lamivudine), and therefore it is classified as a pregnancy category B drug in the treatment and prevention of HIV.
The advantage of telbivudine is that the FDA classifies telbivudine as a pregnancy category B drug, which is a potent, moderately resistant nucleoside analogue, with which it can be used relatively safely in pregnant women. However, research data on mother-to-child blockade is still being accumulated.
3. Women on antiviral therapy should actively use contraception! After achieving the treatment goal and stopping the drug, pregnancy must be considered 6 months after stopping the drug if alpha interferon is used; if a nucleoside analogue is used, pregnancy can be carried out 3 to 6 months after stopping the drug after achieving the treatment goal (the drug has long been completely cleared from the body after 3 months).