Congenital hepatitis B

Congenital hepatitis B is a disease that occurs as a result of intrauterine vertical infection of the fetus with the hepatitis B virus from the mother with HBV infection.

[1], [2], [3], [4], [5], [6]

Prevalence of congenital hepatitis B

The level of carrier of hepatitis B in pregnant women in general coincides with that of the population of the region where they live.

So, in the territory of Northern, Central and Western Europe HBsAg in pregnant women is rarely detected - in 0,12-0,8% of cases, but in the immigrant group the frequency of HBs-antigenemia reaches 5.1-12.5%. In Israel, HBV infection is observed in 0.88% of cases, and in newborns - in 2%.

In the Russian Federation, the frequency of detection of HBcAg in pregnant women ranges from 1 to 5-8%, and in newborns, from 1 to 15.4%.

Causes of congenital hepatitis B

The causative agent of congenital hepatitis B is the hepatitis B virus, transplacental transmitted from mother to fetus. In this case, the hepatitis B virus in pregnant women does not acquire any special properties and has the same structure as the hepatitis B virus that infects individuals in postnatal life.

The development of congenital hepatitis B is usually associated with fetal infection in the II-III trimester of pregnancy. A high risk of infection (with a probability of up to 67%) is present in cases of a mother's acute hepatitis B infection in these periods. At the same time, the full spectrum of markers of replication of the pathogen is found in the blood of the pregnant woman: HBsAg, HBeAg, HBV DNA anti-HBc IgM.

A lower risk of contracting the fetus with an HBV virus is observed when a pregnant woman with chronic hepatitis B or her marker status is treated as a carrier. This is because with chronic hepatitis B in a pregnant woman, a remission with a minimum level of virus reproduction is possible, when the genome of the pathogen is not detected in the serum, although a cow HBeAg polypeptide can be detected with a constant HBe antigenemia; The probability of infection of the fetus in this situation is about 30%.

The status of "carrier" of the HBV virus by the characteristic of replication of the pathogen can vary significantly: from complete prolonged non-recognition of DNA HBV and HBeAg to a periodic or permanent presence of HBV DNA in the serum. Consequently, the carriage of HBV with the presence of HBV DNA in a pregnant woman in the probability of fetal infection approaches the situation with acute hepatitis B.

In the literature there are numerous reports that in pregnant women with HBV virus infection, violations in the placental system are very often recorded, which, apparently, can contribute to the penetration of HBV into the fetus. There are indications that HIV infection in pregnant women serves as a potentiating factor in transferring the fetus from the mother not only to the HCV, but also to HBV.

The fact of intrauterine infection of the HBV fetus was confirmed by the detection of HBsAg in the blood serum and liver homogenates in 7 out of 16 fetuses obtained during abortions from female carriers of the hepatitis B virus. The hepatitis B virus penetrates the fetus due to hepatitis in the liver, where its reproduction begins . Further, the immune reaction of the fetus to infection is formed, which is reflected in the pathomorphological picture of the liver.

[7], [8], [9], [10], [11]

Morphology of congenital hepatitis B

Changes in the liver with congenital hepatitis B are described by leading child pathologists, in particular prof. E.N. Ter-Grigorova. Preservation of the lobular structure of the liver, the severity of portal lymphohystocyte infiltration with a large number of plasma cells are noted. Changes in hepatic cells are polymorphic, against the background of discomplexation of hepatic beams, there are vacuolar and balloon dystrophy of hepatocytes, necrosis of individual hepatocytes. In 50% of cases there is a giant cell transformation of hepatocytes by the formation of multinuclear symplast cells. In the lobules and between the lobes, numerous foci of extramedullary hematopoiesis are formed. Characteristic of cholestasis, manifested as the imbibition of the cytoplasm of hepatocytes by the bile pigment and the presence of biliary thrombi in the enlarged bile capillaries. There is proliferation along the periphery of the cholangiol lobules with cholestasis in their lumens and mononuclear cell infiltrates around them, with the development of cholangitis and pericholangitis.

There are the following variants of morphological changes in the liver with congenital hepatitis B: subacute cholestatic, predominantly giant cell, hepatitis; chronic hepatitis with pericholangiotic fibrosis; cirrhosis of the liver with giant cell metamorphosis of varying severity, as postnecrotic in cases where mothers were ill with severe form of hepatitis.

Symptoms of congenital hepatitis B

Antenatal HBV infection is mainly formed as a primary chronic with a weak clinical picture. Children have decreased appetite, regurgitation, irritability. Jaundice appears on the 2nd-5th day of life, usually weak, and after a few days disappears. Increase in liver size is observed in almost all children; while the liver is palpated from the hypochondrium for 3-5 cm, a dense consistency. In most cases, a simultaneous increase in the spleen is recorded. Characterized extrahepatic signs in the form of telangiectasias, capillaritis, palmar erythema.

According to observations of SM. Bezrodnova (2001), among children with primary-chronic congenital hepatitis, many were observed by a neurologist about various manifestations of perinatal encephalopathy.

Biochemical blood indices indicate a mild violation of the functional state of the liver. Thus, the level of total bilirubin is increased 1.5-2 times, while the levels of conjugated and non-conjugated fractions can be increased equally. The activity indices of ALT and ACT exceed the norm insignificantly - by 2-3 times. Dysproteinemia can be detected by increasing the level of the γ-globulin fraction to 20-2.5%.

When ultrasound is recorded increased echogenicity and increased parenchyma pattern of the liver.

Typical serological markers for this type of congenital hepatitis B are HBsAg, HBeAg and total anti-HBc, not always detectable by HBV DNA.

Significantly less common congenital hepatitis B appears as an acute cyclical disease. Pregnant period is not revealed. Since the birth symptoms of intoxication in the form of lethargy, anxiety, deterioration of appetite are noted, there can be a low-grade fever. Jaundice manifests on the 1-2 day of life, increases within a few days, more often by severity is characterized as moderate. Hepatomegaly is present in all patients with a manifestation process, and most of them have hepatolyenal syndrome. A hemorrhagic syndrome develops in the form of a petechial rash on the skin of the trunk and extremities, and hemorrhages at the injection sites.

Biochemical shifts in serum are expressive. The content of total bilirubin increases 3 to 6 times, the conjugated fraction predominates, though not always. Hyperfermentation is characteristic: ALT activity exceeds the norm by 4-6 times, ACT activity - 3-4 times; can increase the activity of alkaline earth metals and GTPP 2-3 times. The parameters of the prothrombin complex decrease to 50% or more.

In 20-30% of cases, congenital hepatitis B manifests with a pronounced cholestatic syndrome, when jaundice reaches an intense degree, and the level of total bilirubin is 10 times or more higher than normal, and the conjugated fraction is much more prevalent; the activity of alkaline earth metals and GTPP increases substantially. At the same time, in these patients, the activity of ALT and ACT increases slightly - by 2-3 times, in comparison with the norm.

With ultrasound in patients with a manifestation of congenital hepatitis B, high liver echo density, densification of the gallbladder walls are noted; every second patient has an anomaly of gallbladder development, often pancreatopagia. Serologic analysis in these patients shows HBsAg, anti-HBc IgM and IgG classes and not always HBV DNA.

Variants of congenital hepatitis B

Acutely manifesting congenital hepatitis B can be severe; in some cases, taking a fulminant form, ends lethal. However, in most cases, it ends with recovery with a gradual (within 3-7 months) resolution of the disease. For the first time 1-5 months, jaundice disappears, although with the cholestatic variant it is prolonged up to 6 months. The activity of hepatic cell enzymes decreases and after 3-6 months becomes normal. Also, the level of bilirubin decreases, remaining still elevated in the cholestatic variant up to a half-nog. The longest hepatomegaly persists, and in some cases - hepatosplenomegaly - up to 12 months and longer.

However, by the 6th month of life, the overwhelming majority of these patients have seen the disappearance of HBsAg from the circulation and the appearance of anti-HBs. In some children, the seroconversion of HBsAg to anti-HBs occurs later - on the 2nd-3rd month. In all children against the background of HBsAg seroconversion, HBV DNA ceases to be detected. In children with congenital hepatitis B, there is a lag in physical development compared with healthy children - a period of observation of up to 3 years.

A different situation is observed in malosymptomatic primary-chronic congenital hepatitis B. The disease takes a slow character, with a slow normalization of enzyme activity during 7-8 months, but with a further periodic increase of that. Characteristic of stable hepatomegaly or hepatolyenal syndrome, persisting after 12 months of life. This variant of congenital hepatitis B is inherent in prolonged HBs-angiogenesis, which continues in the 2nd and 3rd years of life; HBV DNA is also found in serum for a long time.

Ultrasound reveals a diffuse increase in the echogenicity of the liver parenchyma, which persists during the study in the next few years. In some cases, the formation of liver cirrhosis is documented.

Diagnosis of congenital hepatitis B

Currently, all pregnant women are examined for the presence of markers of the hepatitis B virus, primarily on HBsAg. When ascertaining chronic HBV infection or acute hepatitis B in pregnant women, there is a concern about the possibility of antenatal infection of the fetus and the onset of congenital hepatitis.

For the diagnosis of congenital hepatitis B, the detection of hepatitis B markers in a newborn is crucial. These are HBsAg, anti-HBc IgM, and HBV DNA. There is a need for differential diagnosis of congenital hepatitis B with atresia of extrahepatic bile ducts. With congenital pathology of the biliary tract in the atrezia at the child from birth or during the first month of life, jaundice, fecal decoloration and dark urine are observed. Jaundice is gradually increasing, up to stagnant saffron type. The feces are constantly acholic, urine is intensely colored due to the bile pigment. The liver gradually increases with a gradual consolidation of the parenchema. At the age of 4-6 months of life, the liver becomes dense and very dense due to the formation of biliary cirrhosis. The spleen has not been increased since birth, but it increases with the development of cirrhosis. If for the first time months of life the general state of children changes little, then already at the 3rd and 4th month the lethargy is sharply increased, a bad increase in weight is noted, the volume of the abdomen is increased due to hepatosplenomegaly and flatulence

In the blood serum, the high content of conjugated bilirubin, total cholesterol is constantly recorded, the activity of APP and HPHP, 5-nucleotidase and other liver excreted enzymes is significantly increased, while the activity of ALT, ACT and other hepatic cell enzymes remains within normal limits.

In patients with atresia of extrahepatic bile ducts, markers of hepatitis B virus can be detected, which can be regarded as infection of the vagina by the hepatitis B virus in the early stages of development and the involvement of HBV infection in the formation of this defect. Consequently, the atresia of extrahepatic bile ducts differs from congenital hepatitis B in the clinical picture by the steady progression of jaundice and the symptoms of the emerging biliary cirrhosis.

It is also necessary to exclude jaundice variants caused by conflicts over blood or Rh-factor, as well as defects in the system of erythrocyte enzymes.

In some cases it is necessary to conduct differential diagnosis with other neonatal hepatitis - such as cytometalovirus, toxoplasmosis, chlamydia, etc. Attention is drawn to the obstetrical anamnesis of the mother and the combination of symptoms of liver damage with other manifestations of intrauterine infection (malformations of the central nervous system, heart, kidneys, gastrointestinal tract ). The final differentiation is based on the results of serological studies on the markers of various pathogens of congenital hepatitis, including early IgM class antibodies to pathogens and their genomes.

[12], [13], [14], [15], [16]

Treatment of congenital hepatitis B

In complex treatment for congenital hepatitis B in cases of severe intoxication, detoxifying parenteral therapy is carried out using 5% and 10% glucose solutions, Ringer's solution, rheopolyglucin. When cholestasis is given sorbents, ursophal, hepatoprotector, with a significant increase in the level of free bilirubin, phenobarbital is prescribed.

There are reports of a positive effect of viferon in congenital hepatitis B: under the influence of this interferon alpha, a significantly faster reverse dynamics of clinical and biochemical manifestations of hepatitis and a reduction in the timing of intoxication were observed.

Prevention of congenital hepatitis B

In connection with the fact that with congenital hepatitis B, the child is infected in utero, vaccination is ineffective. However, since it is impossible to decide the issue in which period the infection will occur, all children born from mothers with hepatitis B or virus carriers, necessarily in the first 12 hours from the moment of birth, it is necessary to introduce a vaccine against hepatitis B according to the scheme 0-1-2- 12 months in combination with anti-hepatitis immunoglobulin.