Information for pregnant women with hepatitis B

Hepatitis B is an infectious disease with high morbidity and high infectivity, which seriously jeopardizes human health. Globally, about 2 billion people are infected with Hepatitis B Virus (HBV), and about 350 million people are chronically infected. The younger the age of infection, the higher the probability of becoming a chronic carrier. These chronically infected people have a 15% to 25% risk of dying from HBV-related liver disease, including advanced cirrhosis and hepatocellular carcinoma. China is a high prevalence area for hepatitis B, with HBsAg-positive people amounting to 9.76%, about 130 million people, and the current estimate of the number of patients with active chronic hepatitis B is about 20 million. There are many causes of chronic HBV infection, mainly through blood, mother-to-child and sexual contact. In China, the most important is mother-to-child vertical transmission, and HBV chronic infection caused by mother-to-child vertical transmission accounts for about 30% to 50% of the total. At present, there is no effective antiviral drug for hepatitis B. Literature reports that the incidence of viral hepatitis in pregnant women is 0.8%-17.8%, and severe hepatitis is one of the causes of maternal mortality in China. First, the clinical manifestations of hepatitis B 1, systemic symptoms The liver will affect the whole body, because of the liver function is damaged, hepatitis B patients often feel weak, physical weakness, lower limbs or generalized edema, easy to fatigue, can’t beat the spirit, insomnia, dreamy and other symptoms. A few people will also have flu-like symptoms. 2, digestive symptoms The liver is an important digestive organ of the human body, and patients with hepatitis B often suffer from loss of appetite, nausea, anorexia, epigastric discomfort, bloating and other obvious symptoms due to the reduction of bile secretion. 3.Jaundice Liver is the center of bilirubin metabolism. Hepatitis B patients with increased concentration of bilirubin in the blood will have jaundice, yellowing of the skin and urine, and the urine is in the color of strong tea and other symptoms. 4, pain in the liver area The liver usually does not feel pain, but there are nociceptive nerves distributed in the hepatic peritoneum on the surface of the liver, and when hepatitis B worsens, patients with hepatitis B will have symptoms such as discomfort and vague pain in the right upper abdomen and the right quarter of the ribs. 5.Enlarged liver and spleen Hepatitis B patients often have enlarged liver due to inflammation, congestion, edema and cholestasis. 6, palm performance Many patients with hepatitis B will have liver palm, that is, the surface of the palm will be congestive red, the second ring finger joint of both hands has obvious pressure and pain on the palm surface. 7, skin performance Many patients with chronic hepatitis, especially cirrhosis, have dark or dark color, which may be due to endocrine disorders and symptoms of hepatitis B. The skin of patients with chronic hepatitis, especially cirrhosis, is dark or dark, which may be due to endocrine disorders. At the same time, hepatitis B patients will also appear on the skin, such as spider nevi. Second, the physiological changes of the liver during pregnancy 1, liver histology There is no change in the size and shape of the liver in normal pregnancy, but with the enlargement of the uterus, the position of the liver is slightly shifted upward. It is pushed to the right posterior, so if the liver can be touched in late pregnancy, it is pathologic. In late pregnancy, the systemic blood volume increases by 35% to 40%, but due to fetal shunting, the blood flow to the liver does not increase significantly, while the basal metabolic rate of pregnant women decreases slightly in early pregnancy, and then gradually increases, and can increase by 15% to 20% in late pregnancy, resulting in a relative decrease in hepatic blood flow, a relative lack of hepatic nutrients, and susceptibility to a variety of viral and toxin aggressions. Loss of appetite, nausea and vomiting during pregnancy reactions can further affect the intake of liver nutrients. Since blood lipid levels increase throughout pregnancy, there is mild fat deposition in the liver, mainly cholesterol and triglycerides, and non-specific changes in liver tissue are seen. This change helps to store energy for metabolic needs in case of starvation and undernutrition. Because of the dilatation of the gallbladder during pregnancy, the cholesterol level in the bile increases, so pregnant women are prone to gallstones. Liver function Some liver function tests may mildly exceed the normal value in late pregnancy and return to normal quickly after delivery. About half of the total serum protein in late pregnancy is less than 60g/L, mainly due to blood dilution. Plasma albumin decreases, globulin slightly increases due to hyperfunction of the hepatic reticuloepithelial system, and the ratio of albumin to globulin (A/G) decreases. In a few pregnant women, serum alanine aminotransferase (ALT) and mentholatum aminotransferase (AST) are slightly elevated in late pregnancy. Serum alkaline phosphatase (ALP) is elevated and the cause may be primarily from the placenta. Coagulation factors II, V, VII, VIII, IX, and X are increased, and fibrinogen is increased by about 50%. Serum cholesterol, triglycerides, total lipids, phospholipids, and alpha and beta lipoproteins are increased. Estrogen level rises during pregnancy, some pregnant women show “liver palms” and “spider nevus”, and aggravated with the progression of pregnancy, and disappeared 4-6 weeks after delivery. Third, the impact of pregnancy on hepatitis B pregnancy itself does not increase the susceptibility to hepatitis virus, but the physiological changes and metabolic characteristics of pregnancy, so that the liver’s ability to fight disease decreases and the burden on the liver increases, which can worsen the condition of hepatitis B and increase the difficulty of diagnosis and treatment of severe hepatitis and hepatic encephalopathy occurs in non-pregnancy 37-65 times higher than the incidence of the disease. Liver damage caused by pregnancy complications is very easy to be confused with acute viral hepatitis, which makes diagnosis and treatment more difficult. Fourth, the impact of hepatitis B on the mother and child The combination of viral hepatitis in early pregnancy can make the pregnancy reaction worse, the incidence of miscarriage and fetal malformation is about two times higher. And it is a common cause of jaundice in pregnancy, including hepatitis A, hepatitis B, hepatitis C, hepatitis D and hepatitis E. In late pregnancy, it may cause jaundice in pregnancy. It may increase the incidence of gestational hypertension in late pregnancy, possibly related to the decreased hepatic inactivation of aldosterone; the incidence of postpartum hemorrhage is significantly higher, as well as the incidence of severe hepatitis, which is 66 times higher than that of non-pregnant women. Maternal deaths due to acute severe hepatitis are rare in developed countries, about 1.2%. In developing countries, such as India, Central Asia and Africa, severe acute hepatitis, especially in late pregnancy, causes about 30% of maternal deaths. Poor nutritional status and lack of antenatal checkups may contribute to the high maternal mortality due to hepatitis in developing countries. Combined viral hepatitis in pregnancy may also increase the risk of preterm labor during late pregnancy. Preterm labor occurs in 25% of pregnant women with acute viral hepatitis in developed countries, with a perinatal mortality rate of 8%, while in India and Central Asia the perinatal mortality rate is as high as 50%. V. Pathways of mother-to-child transmission of hepatitis B virus 1. Intrauterine transmission (1) Placental pathway In the past, it was thought that hepatitis B virus seldom passes through the placenta. In recent years, more information proves that the rate of intrauterine infection is high, and the intrauterine infection caused by placenta is about 5%~10%. It is believed that HBV intrauterine infection is mainly due to the damage or permeability change of placental barrier caused by HBV. The higher the degree of maternal blood infection, the more likely placental infection. Placenta infected with HBV and fetal infection, but the placenta by HBV infection, not necessarily make the fetus infected, the placenta to a certain extent on the fetus has a protective effect. Some experiments also showed that from early pregnancy to full-term delivery, placental HBV infection has gradually increased. (2) PBMCs pathway Chorionic villous rupture during pregnancy and delivery can cause a small number of maternal leukocytes to pass through the placental barrier to the fetus, and HBV can also invade peripheral blood single nucleated cells to form a latent infection. HBV-infected PBMCs may pass through the intact placenta to infect the fetus, preterm labor, preterm delivery, and TORCH infections can cause destruction of placental tissues, the formation of placental fissures, and destruction of placental barriers. The placental barrier is destroyed, the mother’s blood mixes directly with the umbilical cord blood, and the HBV in the mother’s blood serum and PBMCs can enter the fetal circulation directly, causing intrauterine infection. (3) Transmission through germ cells In vitro test shows that normal human live sperm can capture HBV DNA, and the distribution of captured HBV DNA in sperm is the same as that of sperm of hepatitis B patients. It can be seen that HBV can exist in sperm and semen, and replicate in it, and even integrated in sperm chromosome, on the one hand, it causes aberration to sperm itself, on the other hand, it is the main way to cause the transmission of HBV, especially the transmission from father to child. 2.Natal transmission: It is the main way of HBV transmission from mother to child, accounting for 40%~60%. When the fetus passes through the birth canal, it swallows mother’s blood, amniotic fluid and vaginal secretion containing HBsAg, or the uterine contraction during delivery ruptures the placenta chorionic villi, and the mother’s blood leaks into the fetus’s blood circulation. 3, postnatal transmission: related to contact with breast milk and mother’s saliva. It is reported that when the mother’s blood HBsAg, HBeAg, anti-HBc are positive breast milk HBV-DNA rate of 100%, pure HBsAg positive, breast milk HBV-DNA rate of about 46%. Methods of mother-to-child transmission interruption 1. Establishment of a comprehensive perinatal health care system Screening, management and monitoring of HBV-infected pregnant women, and testing and follow-up of newborns to determine whether fetal infection. Whether hepatitis virus can cause fetal malformation is not conclusive, however, there are reports of increased incidence of congenital stupidity, early pregnant women with high HBsAg titer and HBeAg positive to terminate the pregnancy. newborns of HBV-infected pregnant women are showered immediately after birth, and breastfeeding is stopped and the mother is isolated for 4 weeks. 2, immunoprophylaxis (1) Hepatitis B vaccine At present, China mainly uses genetically recombinant yeast hepatitis B vaccine, 5 μg each time, according to the procedure of vaccination in the 0th, 1st month and 6th month. The protection rate of pure routine hepatitis B vaccination for newborns whose mother’s blood is positive for both HBsAg and HBeAg is 43%, and the protection rate of HBsAg infection after increasing the vaccine dose is only 80%. Since the inclusion of hepatitis B vaccine in the immunization program in 2002, the infection rate of children has been greatly reduced since the universal vaccination of newborns with hepatitis B. 70% of immunization failures of infants born to HBeAg-positive mothers who were immunized with hepatitis B vaccine alone to interrupt mother-to-child transmission were due to intrauterine infections, and almost all of those who failed to be immunized with the combined immunization were due to intrauterine infections. Therefore, it is recommended to increase the dosage of hepatitis B vaccine or use hepatitis B vaccine and HBIG combined immunization to reduce the incidence of mother-to-child transmission. (2) High-valence hepatitis B immunoglobulin (HBIG) Studies on prenatal blockade show that giving hepatitis B HBIG to pregnant women from the late 28th week of gestation until delivery can significantly reduce the rate of intrauterine infection. The mechanism is to reduce the maternal viral load as much as possible in the prenatal period, and more importantly, because hepatitis B HPV immunoglobulin can pass through the placenta, and the placenta has the function of actively transferring IgG-type antibodies from the mother to the fetus, therefore, for serum HBsAg-positive mothers, after repeated HPV immunoglobulin injections during pregnancy, the anti-HBs can be transferred to the fetus through the placenta, which can provide passive immunity protection and prevention of intrauterine infections in the uterus. If hepatitis B immunoglobulin (HBIG) and hepatitis B vaccine are injected immediately after birth, the protection rate against HBV infection can be increased to more than 92%. The protection rate can be further increased to 97% if hepatitis B HBIG and hepatitis B vaccine are injected 1 month after birth. Therefore, for newborns whose mother’s blood is positive for both HBsAg and HBeAg, a combined blockade regimen of hepatitis B vaccine and hepatitis B immunoglobulin should be used, and if immunization is successful, 27% of infants will be anti-HBc positive. For HBsAg-positive and HBeAg-negative newborns, better results can be obtained by routinely administering 20ug of hepatitis B vaccine according to the 0-1-6 regimen within 24h after birth. Therefore, prevention of HBV transmission in the perinatal period is of great significance. 3.Nucleoside antiviral drugs It has been clear that the probability of mother-to-child transmission of HBV is closely related to the HBV replication status in the mother. If HBV replication can be effectively inhibited, the success rate of mother-to-child transmission interruption will be greatly improved. Nucleoside antiviral drugs have been used for many years in the treatment of chronic HBV infection, and a wealth of clinical experience has been gained. Levamisole is a non-specific immunomodulator, mainly acting on T cells, inducing early pre-T cell differentiation and maturation, becoming functional T cells and can make dysfunctional T cells back to normal, while enhancing the chemotaxis and phagocytosis of monocytes, activating the macrophage and granulocyte movement inhibitory factors, inducing endogenous interferon, improving the immune and viral efficacy, and has been used in the treatment of chronic hepatitis B. 4, on the issue of cesarean section Cesarean section can prevent the fetus from inhaling infected birth secretions during delivery, but studies have found that cesarean section has little preventive effect, and intraoperative hemorrhage, the baby is exposed to a large number of infected mother’s blood, so cesarean section can’t reduce the rate of neonatal HBV infection. HBV carried by pregnant women can be transmitted vertically to infect the fetus. mother-to-child transmission of HBV is an important route of transmission of hepatitis B. If it can be completely blocked, it will play a key role in controlling or even eradicating hepatitis B. Active and passive immunization of HBsAg-positive pregnant women can effectively reduce the rate of intrauterine infection. People’s understanding of HBV mother-to-child transmission and China’s research on interruption measures have made great progress, but there is still a big gap from the realistic requirements, and in-depth research is needed to elucidate the mechanism and correctly evaluate and actively promote all effective interruption measures.