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 a mother with HBV infection.

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Prevalence of congenital hepatitis B

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

Thus, in the territory of Northern, Central and Western Europe, HBsAg is rarely detected in pregnant women - in 0.12-0.8% of cases, but in the group of immigrants 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, which is transmitted transplacentally from mother to fetus. In this case, the hepatitis B virus in a pregnant woman does not acquire any special properties and has the same structure as the hepatitis B virus infecting individuals in postnatal life.

The development of congenital hepatitis B is usually associated with infection of the fetus in the II-III trimester of pregnancy. There is a high risk of infection (with a probability of up to 67%) if the mother is ill with acute hepatitis B during the specified periods. In this case, the pregnant woman's blood contains a full range of pathogen replication markers: HBsAg, HBeAg, HBV DNA anti-HBc IgM.

A lower risk of fetal infection with the HB virus is observed when the pregnant woman has chronic hepatitis B or her marker status is assessed as a carrier. This is explained by the fact that with chronic hepatitis B, a pregnant woman may experience remission with a minimal level of virus reproduction, when the pathogen genome is not detected in the blood serum, although the bovine polypeptide HBeAg may be detected with constant HBe antigenemia; the probability of fetal infection in this situation is about 30%.

The status of "carrier" of the HB virus according to the characteristics of the pathogen replication can vary significantly: from complete long-term undetectable DNA of HBV and HBeAg to periodic or constant presence of DNA of HBV in the blood serum. Consequently, the carriage of HBV with the presence of DNA of HBV in the blood of a pregnant woman in terms of the probability of infection of the fetus approaches the situation with acute hepatitis B.

There are numerous reports in the literature that pregnant women with HBV infection very often have disturbances in the placental system, which, apparently, can facilitate the penetration of the HBV into the fetus. There are indications that HIV infection in a pregnant woman serves as a potentiating factor in the transmission of not only НСV but also НВV from the mother to the fetus.

The fact of intrauterine infection of the fetus with HBV was confirmed by the detection of HBsAg in the blood serum and liver homogenates in 7 of 16 fetuses obtained during abortions from women - carriers of the hepatitis B virus. The hepatitis B virus that has penetrated the fetus's body, due to its hepatotropism, ends up in the liver, where it begins to reproduce. Then, the immune response of the fetus to the infection is formed, which is reflected in the pathomorphological picture of the liver.

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Morphology of congenital hepatitis B

Liver changes in congenital hepatitis B have been described by leading pediatric pathologists, in particular, Professor E. N. Ter-Grigorova. Preservation of the lobular structure of the liver, severity of portal lymphohistiocytic infiltration with a large number of plasma cells are noted. Changes in liver cells are polymorphic, against the background of discomplexation of the liver beams, vacuolar and balloon dystrophy of hepatocytes, necrosis of individual hepatocytes are observed. In 50% of cases, there is giant cell transformation of hepatocytes by the formation of multinuclear symplast cells. Numerous foci of extramedullary hematopoiesis are formed in the lobules and between the lobules. Cholestasis is characteristic, manifested in the form of imbibition of the cytoplasm of hepatocytes by bile pigment and the presence of bile thrombi in the dilated bile capillaries. Proliferation is observed along the periphery of the cholangioli lobules with cholestasis in their lumens and mononuclear cellular infiltrates around them, with the development of cholangitis and pericholangitis.

The following variants of morphological changes in the liver in congenital hepatitis B are distinguished: subacute cholestatic, predominantly giant cell, hepatitis; chronic hepatitis with pericholangiolytic fibrosis; cirrhosis of the liver with giant cell metamorphosis of varying severity, such as postnecrotic in cases where mothers suffered from a severe form of hepatitis.

Symptoms of congenital hepatitis B

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

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

Biochemical blood parameters indicate a mild impairment of the functional state of the liver. Thus, the level of total bilirubin is increased by 1.5-2 times, while the levels of conjugated and non-conjugated fractions can be increased equally. ALT and AST activity parameters exceed the norm slightly - by 2-3 times. Dysproteinemia can be detected due to an increase in the level of the y-globulin fraction to 20-2.5%.

Ultrasound shows increased echogenicity and enhanced liver parenchyma pattern.

Characteristic serological markers for this type of congenital hepatitis B are HBsAg, HBeAg and total anti-HBc; HBV DNA is not always detected.

Much less frequently, congenital hepatitis B manifests itself as an acute cyclic disease. The pre-icteric period is not detected. Symptoms of intoxication in the form of lethargy, anxiety, loss of appetite, and a subfebrile temperature are observed from birth. Jaundice manifests itself on the 1st or 2nd day of life, intensifies over several days, and is often characterized by its severity as moderate. Hepatomegaly is present in all patients with a manifest process, and most of them have hepatosplenic syndrome. Hemorrhagic syndrome develops in the form of a petechial rash on the skin of the trunk and extremities, and hemorrhages at injection sites.

Biochemical changes in the blood serum are significant. The total bilirubin content increases 3-6 times, the conjugated fraction predominates, although not always. Hyperfermentemia is characteristic: ALT activity exceeds the norm by 4-6 times, AST activity - by 3-4 times; the activity of alkaline phosphatase and GPTP may increase by 2-3 times. The prothrombin complex indicators decrease to 50% or more.

In 20-30% of cases, congenital hepatitis B manifests with pronounced cholestatic syndrome, when jaundice reaches an intense degree, and the level of total bilirubin is 10 times or more higher than normal, with the conjugated fraction significantly predominating; the activity of alkaline phosphatase and GTTP increases significantly. At the same time, in these patients, the activity of ALT and AST increases slightly - 2-3 times, compared to the norm.

Ultrasound examination of patients with manifest congenital hepatitis B reveals increased liver echo density, thickening of the gallbladder walls; every second patient has an abnormal development of the gallbladder, often pancreatopagia. Serological analysis of these patients reveals HBsAg, anti-HBc classes IgM and IgG, and not always HBV DNA.

Variants of the course of congenital hepatitis B

Acutely manifesting congenital hepatitis B can proceed severely; in some cases, taking a fulminant form, it ends fatally. However, in most cases it ends with recovery with a gradual (within 3-7 months) resolution of the disease. For the first time, jaundice disappears in 1-5 months, although in the cholestatic variant it lasts up to 6 months. The activity of liver-cell enzymes decreases and after 3-6 months becomes normal. The bilirubin level also decreases, although it remains elevated in the cholestatic variant up to half a point. Hepatomegaly persists the longest, and in some cases - hepatosplenomegaly - up to 12 months and longer.

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

A different situation is observed in low-symptom primary chronic congenital hepatitis B. The disease takes on a sluggish nature, with slow normalization of enzyme activity over 7-8 months, but with subsequent periodic increase in it. Characteristic are persistent hepatomegaly or hepatosplenic syndrome, persisting after 12 months of life. This variant of congenital hepatitis B is characterized by prolonged HBs-angigenemia, continuing in the 2nd and 3rd years of life; in this case, HBV DNA is also detected in the blood serum for a long time.

Ultrasound reveals a diffuse increase in the echogenicity of the liver parenchyma, which persists during examination over the next several years. In some cases, the development of liver cirrhosis is noted.

Diagnosis of congenital hepatitis B

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

For diagnostics of congenital hepatitis B, detection of hepatitis B markers in a newborn is of crucial importance. These are HBsAg, anti-HBc IgM and HBV DNA. There is a need for differential diagnostics of congenital hepatitis B with atresia of the extrahepatic bile ducts. In case of congenital pathology of the biliary tract due to atresia, a child has jaundice, discolored stool and dark urine from birth or during the first month of life. Jaundice gradually increases, up to a stagnant saffron appearance. Stool is constantly acholic, urine is intensely colored due to bile pigment. The liver gradually increases with gradual compaction of the parenchyma. At the age of 4-6 months of life, the liver becomes dense and very dense due to developing biliary cirrhosis. The spleen is not enlarged from birth, but increases as cirrhosis develops. If in the first months of life the general condition of children changes little, then already in the 3rd-4th month lethargy increases sharply, poor weight gain is noted, the volume of the abdomen increases due to hepatosplenomegaly and flatulence

The blood serum constantly shows high levels of conjugated bilirubin and total cholesterol, significantly increased activity of alkaline phosphatase and GPGP, 5-nucleotidase and other enzymes excreted by the liver, while the activity of ALT, AST and other liver cell enzymes remains within normal limits.

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

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

In some cases, differential diagnostics with other neonatal hepatitis should be performed, such as cytometallovirus, toxoplasmosis, chlamydial, etc. In this case, attention should be paid to the mother's obstetric history and the combination of symptoms of liver damage with other manifestations of intrauterine infection (malformations of the central nervous system, heart, kidneys, gastrointestinal tract). Final differentiation is carried out based on the results of serological studies for markers of various pathogens of congenital hepatitis, including early IgM antibodies to pathogens and their genomes.

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Treatment of congenital hepatitis B

In complex treatment of congenital hepatitis B in cases of severe intoxication, detoxifying parenteral therapy is performed using 5% and 10% glucose solutions, Ringer's solution, rheopolyglucin. In case of cholestasis, sorbents, ursofal, hepatoprotector are given, and in case of 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 duration of intoxication were observed.

Prevention of congenital hepatitis B

Since congenital hepatitis B is acquired in utero, vaccination is ineffective. However, since it is impossible to determine when the infection will occur, all children born to mothers with hepatitis B or carriers of the virus must be given the hepatitis B vaccine within 12 hours of birth according to the 0-1-2-12 month schedule in combination with antihepatitis immunoglobulin.