Management of pregnancy in chronic HBV-infected patients
1. Timing of pregnancy.
Before a woman with chronic HBV infection plans to become pregnant, it is best to have her liver function evaluated by a specialist in infection or hepatology. Infected patients whose liver function is always normal can have a normal pregnancy; those with abnormal liver function can have a pregnancy if they return to normal after treatment and are rechecked normal for more than 6 months after stopping medication.
Pregnancy during antiviral therapy must be done with caution. Interferon can inhibit fetal growth and contraception must be used during its use. Among the nucleoside (acid) analogues, adefovir and entecavir have adverse effects on fetal development or teratogenic effects [2] and are contraindicated in the first 6 months of pregnancy and during pregnancy. Tenofovir and telbivudine belong to pregnancy drug class B [2] and have no significant effect on the fetus when used in mid- to late pregnancy. Lamivudine belongs to class C drugs but does not increase neonatal birth defects when used in early, mid and late pregnancy to prevent mother-to-child transmission of HIV [3]. Nevertheless, if pregnancy occurs during the use of any antiviral drug, the patient must be informed of the various risks of the drug used and a consultation with the relevant physician must be requested to decide whether to interrupt the pregnancy or to continue antiviral therapy.
2.Follow-up of pregnant women.
After pregnancy, chronic HBV-infected patients must have their liver function reviewed regularly, especially in the early and late stages of pregnancy. If the liver function is normal in the first test, if there are no clinical symptoms of hepatitis, it should be rechecked once every one to two months; if the alanine transferase (ALT) is elevated but not more than two times the normal value (<80U/L) and there is no elevated bilirubin level, there is no need for medication, but rest is still needed and rechecked at intervals of one to two weeks; if the ALT level is elevated more than two times the normal value (>80U/L) or the bilirubin level is elevated. If the ALT level rises more than twice the normal value (>80U/L) or the bilirubin level rises, it is necessary to consult the relevant professional physician, and if necessary, hospitalization, and in serious cases, termination of pregnancy.
3. The use of HBIG in late pregnancy has no effect on the prevention of mother-to-child transmission.
It has been proposed that the application of HBIG to HBV-infected pregnant women in late pregnancy can prevent intrauterine infection of the fetus, but the following problems exist in related studies.
(1) The protection rate of neonates in the control group after immunoprophylaxis was only 55%~85%, which was significantly lower than the accepted protection rate, suggesting that there was no formal prevention in the control group;
(2) The diagnostic criteria were incorrect and exaggerated the rate of intrauterine infection;
(3) Some studies had contradictory results before and after themselves. In addition, there was no anti-HBS in the newborn after HBIG in pregnant women [4]; gorilla experiments and studies on prevention of reinfection after liver transplantation in HBV-infected patients suggest that HBIG injections of 200-400 U every 4 weeks during late pregnancy are unlikely to reduce HBV viral load [5]; it has also been reported in China that this regimen does not reduce mother-to-child transmission [6-7]. Therefore, it is not necessary to apply HBIG to HBV-infected pregnant women in late pregnancy.
4, Problems of antiviral therapy during pregnancy.
High levels of HBV in pregnant women are the main risk factor for the occurrence of mother-to-child transmission, and reducing the viral load can reduce mother-to-child transmission. When pregnant women are HBsAg positive but HBeAg negative, their newborns have achieved 98% to 100% protection after regular prophylaxis [7-9]. Therefore, there is no need to use antiviral therapy to prevent mother-to-child transmission in HBeAg-negative infected pregnant women.
Chronic HBV infection still occurs in 5%-15% of newborns of HBeAg-positive pregnant women after formal prophylaxis [7-9]. Although, treatment with lamivudine or telbivudine in mid- and late pregnancy has been reported to reduce mother-to-child transmission [10-12], some of these studies had a small number of cases [IO], and some control neonates may not have been formally prophylactic [11], or mother-to-child transmission still occurred after treatment [10-11,13]. Therefore, HBeAg-positive pregnant women cannot be routinely treated with antiviral therapy as an indication to reduce mother-to-child transmission at this time.
The following factors also justify the need for caution in anti-HBV therapy in pregnant women.
(1) Nucleoside (acid) analogs do not clear the virus and upon discontinuation the virus will return to its original level or even higher, even inducing severe liver function damage;
(2) Long-term use of drugs will increase the financial burden and make the virus mutate and produce drug resistance and other side effects;
(3) 85%-95% of HBeAg-positive pregnant women can be protected by regular prophylaxis of their newborns even without anti-HBV treatment;
(4) Anti-HBV therapy usually starts in mid- and late pregnancy and is not effective for intrauterine infection in early and mid pregnancy.
In conclusion, whether anti-HBV therapy is needed to reduce mother-to-child transmission in HBeAg-positive pregnant women remains to be studied in more rigorously designed, rigorously controlled, large-sample, multicenter studies.
In addition, abnormal liver function during pregnancy in HBV-infected patients does not increase the risk of mother-to-child transmission of HBV [8-9], and most pregnant women will return to normal liver function after delivery. Therefore, routine anti-HBV therapy cannot be administered to those with abnormal liver function, and the indications for anti-HBV therapy should be strictly controlled.
Cesarean delivery cannot reduce mother-to-child transmission
It was previously believed that the contraction of the uterus during natural delivery “squeezes” the placenta, prompting the virus in the mother to enter the fetus and cause intrauterine infection, so theoretically cesarean delivery can reduce the mother-to-poppy transmission of HBV [14]. However, recent studies have shown that there is no statistically significant difference between the rate of HBV infection in newborns delivered by curettage and those delivered spontaneously after formal prophylaxis in chronically infected pregnant women (P>0.05) [15], indicating that curettage does not reduce the mother-to-child transmission of HBV. Therefore, cesarean delivery cannot be chosen for the purpose of interrupting mother-to-child transmission of HBV [16].
IV. Prevention of mother-to-child transmission of HBV
Vaccination against hepatitis B is the most effective measure to prevent HBV infection, and the active ingredient of hepatitis B vaccine is HBsAg, which works by inducing the body to actively produce anti-HBs. After the first vaccination, most anti-HBs are still negative or below the lower limit of detection; anti-HBs turn positive only about l week after the second vaccination [17], i.e., immunity to HBV 35-40 d after the start of vaccination; pressing the third vaccination can lead to a significant increase in the level of anti-HBs and prolong the years of protection. The positive conversion rate of anti-HBs after full vaccination of neonates is as high as 95%-100% [8,18], and the protection period can be more than 22 years [19]. After the body actively produces anti-HBs, it has immune memory, and even if anti-HBs turn negative, the body can produce anti-HBs within a short period of time when exposed to HBV again [19]; therefore, booster vaccination against hepatitis B is not needed for non-high-risk groups.
Key points of neonatal hepatitis B immunoprophylaxis
1, all pregnant women need to be tested for hepatitis B serologic markers before delivery: HBsAg positive, indicating that they have HBV infection and are infectious; HBeAg positive, highly infectious; and anti-one HBs positive, immune to hepatitis B.
2, HBsAg negative pregnant women: newborns are vaccinated with hepatitis B vaccine according to the 3-dose program at 0, 1 and 6 months, i.e. 1 dose at 1 month and 6 months respectively within 24h of birth; it is not necessary to inject HBIG again.
3.Pregnant women with positive HBsAg: newborns are given one intramuscular injection of HBIG within 12h of birth; at the same time, they are vaccinated with hepatitis B vaccine according to the 3-dose program at 0, 1 and 6 months.
4, HBsAg-positive pregnant women’s breastfeeding: after the formal prevention of newborns, regardless of whether the pregnant women are HBeAg negative or positive, breastfeeding is feasible.
5, mode of delivery and mother-to-child transmission: cesarean delivery cannot reduce the rate of mother-to-child transmission of HBV.
6, preterm infants: when the birth mass ≥ 2000g, no special treatment. When the body mass <2000g, the first vaccination will be given after the body mass reaches 2000g, and then after an interval of 1-2 months, the 3-dose program will be implemented according to 0, 1 and 6 months. If the pregnant woman is HBsAg negative and the premature baby is in good health, deal with it as above; if the health condition is not good, deal with the related disease first and wait for recovery before vaccination. If the pregnant woman is HBsAg positive, regardless of the health condition of the premature baby, the vaccine will be injected intramuscularly within 12 hours.
7, other family members HBsAg positive: If the newborn is in close contact with HBsAg positive members, HBIG must be injected; not in close contact, no injection is necessary.
8, follow-up of newborns of HBsAg-positive pregnant women: at 7-12 months, test for serological markers of hepatitis B. If HBsAg negative, anti- a HBs positive, prevention is successful and resistant; if HBsAg negative, anti-, HBs negative, prevention is successful, but need another 3 doses of vaccination program; if HBsAg positive, prevention fails and become chronic infected.
9, other precautions: before any operation that damages the skin mucosa, it must be fully cleaned and disinfected before proceeding.
10.Whether to perform anti-HBV treatment for HBsAg-positive pregnant women to reduce the rate of mother-to-child transmission: when HBeAg-negative, no antiviral is needed; when HBeAg-positive, whether anti-HBV treatment should be performed is inconclusive and requires a rigorous multi-center controlled study.