I. Clinical diagnosis of HBV infection
Chronic HBV infection is defined as HBsAg positivity lasting for more than 6 months. If the liver function is normal, it is called chronic HBV carrier; if the liver function is abnormal and other causes are excluded, the diagnosis is chronic hepatitis B. Chronic HBV carriers need to review the liver function and other necessary tests every 6-12 months.
Mother-to-child transmission of HBV, i.e. HBsAg-positive maternal transmission of HBV to the offspring, occurs mainly during and after delivery, while vertical transmission (intrauterine infection before delivery) has an infection rate of <3%. It is mostly seen in hbeag-positive pregnant women.
The presence or absence of infection or immunity can be determined by testing for serologic markers of hepatitis B, namely HBsAg, hepatitis B surface antibody (anti-HBs), HBeAg, hepatitis B e antibody (anti-HBe), and hepatitis B core antibody (anti-HBc).
A positive HBsAg indicates that the virus is replicating and is infectious; a positive HBeAg is a sign of active virus replication and high viral load, and is highly infectious. Anti-HBs is a neutralizing antibody, and serum anti-HBs level ≥10 mIU/ml is protective. Fluorescence real-time quantitative PCR technique detects HBV DNA level, which can reflect the level of viral load.
However, about 30% of pregnant women who are HBsAg positive and HBeAg negative (commonly known as minor triplets), or even a few HBeAg positive (commonly known as major triplets), have HBV DNA below the lower limit of detection, which is called “HBV DNA negative”, but still have HBV in their blood and are infectious. Therefore, when a pregnant woman is HBsAg positive, regardless of her HBV DNA level, or even “negative”, her newborn will have the possibility of infection if she does not take immunoprophylaxis.
Second, the management of chronic HBV-infected patients during pregnancy
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 the growth of the popular child 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 and are contraindicated in the first 6 months of pregnancy and during pregnancy. Tenofovir and telbivudine belong to pregnancy drug class B and have no significant effect on the fetus when used in mid- to late pregnancy. b Lamivudine belongs to class C, but does not increase neonatal birth defects when used to prevent HIV I mother-to-child transmission in early, mid- and late pregnancy.
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 should be requested to decide whether to interrupt the pregnancy or to continue antiviral therapy.
2. Pregnancy follow-up: After pregnancy, liver function must be reviewed regularly in chronic HBV-infected patients, 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, the test should be repeated once every 1 to 2 months; if the alanine transferase (ALT) is elevated but does not exceed 2 times the normal value (<80 U/L) and there is no elevated bilirubin level, there is no need for drug treatment, but rest is still needed and the test should be repeated at intervals of 1 to 2 weeks; if the ALT level is elevated more than 2 times the normal value (>80 U/L) or the bilirubin level is elevated. If the ALT level rises more than twice the normal value (>80 U/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 application of HBIG in late pregnancy has no role in the prevention of mother-to-child transmission: some scholars have proposed that the application of HBIG in HBV-infected pregnant women in late pregnancy can prevent intrauterine infection in 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-HBsAb in newborns after HBIG in pregnant women; gorilla experiments and studies on the 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 the amount of HBV virus; it has also been reported in China that the regimen does not reduce mother-to-child transmission. Therefore, it is not necessary to apply HBIG to HBV-infected pregnant women in late pregnancy.
4, the problem of antiviral treatment during pregnancy: high levels of HBV in pregnant women is the main risk factor for the occurrence of mother-to-child transmission, and reducing the amount of virus can reduce mother-to-child transmission. When pregnant women are HBsAg positive but HBeAg negative, their newborns have a protection rate of 98%-100%¨ after regular prevention. 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’. Although, it has been reported that in the middle and late stages of pregnancy
treatment with lamivudine or telbivudine can reduce mother-to-child transmission, but some of these studies had a small number of cases, and some control neonates may not have had formal prophylaxis, or mother-to-child transmission still occurred after treatment. Therefore, HBeAg-positive pregnant women cannot be routinely treated with antiviral therapy as an indication for reducing mother-to-child transmission at this time.
The following factors are also reasons 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.