What is Viral Hepatitis B?
Viral hepatitis B is an anthroponotic viral infection from the conditional group of transfusion hepatitis, characterized by immunologically mediated lesion of hepatocytes and occurring in various clinical forms (from virus carriage to liver cirrhosis).
For a long time, viral hepatitis B was called serum, parenteral, iatrogenic, post-transfusion, syringe. This emphasized the parenteral route of transmission of the pathogen through damaged skin and mucous membranes (unlike the virus of hepatitis A, which is transmitted through the fecal-oral route).
In 1963, B. Blumberg first isolated from the blood of the Australian Aborigines a special “Australian antigen”, which later became considered a marker of serum hepatitis. Later, D. Dein (1970) first identified a new hepatitis virus, thereby substantiating the existence of a new nosological form – viral hepatitis B.
Causes of Viral Hepatitis B
The causative agent of viral hepatitis B is a DNA-genomic virus of the genus Orthohepadnavirus of the Hepadnaviridae family. In the blood of patients with viral hepatitis B particles of three morphological types circulate. Spherical particles are found most often, less often – filamentary forms. Virus particles of these types do not exhibit infectious properties. Only 7% of the particles are represented by complex bilayer spherical formations with a full structure (the so-called Dane particles), showing pronounced infectivity. Their upper layer forms a supercapsid. The genome is represented by an incomplete (one strand shorter) double-stranded circular DNA molecule and its associated DNA polymerase. Four antigens are isolated from virions – surface (HBsAg) and three internal (HBeAg, HBcAg and HBxAg).
The main antigens of Dane particles are surface HBsAg and core HBcAg. Antibodies against HBsAg and HBcAg appear during the course of the disease. The increase in antibody titer against HBcAg is directly related to the formation of antiviral immune responses, HBcAg (core, or core, antigen) plays an important role in the reproduction of the virus. In the infectious process, it is detected only in the nuclei of hepatocytes. HBeAg is localized not only in the core of the virus, it circulates in the blood in a free form or associated with antibodies. It is defined as an infectious antigen. HBsAg (surface antigen) determines the ability for long-term persistence of the virus in the body; It has relatively low immunogenicity, thermal stability, and resistance to proteases and detergents. There are several subtypes of HBsAg that differ in subdeterminants: adw, adr, ayw, ayr. A common antigenic determinant is a determinant, so post-vaccination immunity is protective against any subtype of the virus. In Ukraine, subypes ayw and adw are mainly registered. Clinical manifestations of the disease do not depend on the subtype of the virus. HBxAg remains the least studied. Presumably it mediates the malignant transformation of liver cells.
The virus of hepatitis B is extremely resistant to the environment. In whole blood and its preparations is preserved for years. Virus antigen is detected on bedding, medical and dental instruments, needles contaminated with blood serum (when stored for several months at room temperature). The virus is inactivated after autoclaving at 120 ° С in 45 minutes, sterilization by dry heat at 180 ° С in 60 minutes. Hydrogen peroxide, chloramine, formalin is detrimental to it.
The source of infection is persons with manifest or subclinical forms of the disease (patients with acute and chronic hepatitis, with cirrhosis of the liver and the so-called “healthy” virus carriers). In the patient’s blood, the virus appears long before the onset of the disease (2-8 weeks before the activity of aminotransferases is increased) and circulates during the entire acute period of the disease, as well as during chronic carrier state, which forms in 5-10% of cases. According to experts, there are 300-350 million virus carriers in the world, each of which represents a real threat as a source of infection. The contagion of infection sources determines the activity of the pathological process in the liver and the concentration of antigens of viral hepatitis B in the blood.
The mechanism of transmission of viral hepatitis B. The isolation of a virus with various biological secrets (blood, saliva, urine, bile, tears, breast milk, sperm, etc.) determines the multiplicity of ways of transmission of infection. However, only blood, semen and, possibly, saliva represent a real epidemiological danger, since in other fluids the concentration of the virus is very low. The disease is transmitted mainly by parenteral transfusions of blood and blood substitutes, when using medical instruments without their sufficiently effective sterilization. The percentage of post-transfusion viral hepatitis B has significantly decreased in recent years. Still often, patients are infected during the implementation of various therapeutic and diagnostic procedures, accompanied by a violation of the integrity of the skin or mucous membranes (injections, dental procedures, gynecological examination, etc.).
Of the natural transmission mechanisms, the contact (sexual) path is realized, as well as the transmission of the virus through various contaminated household items (razors, toothbrushes, towels, etc.) when the pathogen enters the body through microtrauma on the skin and mucous membranes. Infection also occurs as a result of tattooing, piercing earlobes and other manipulations. Sexual transmission of viral hepatitis B is realized through homo-and heterosexual contacts: the virus penetrates mucus microtraumas through sexual contact. Contact-household transmission of infection – intrafamily infection, infection in organized groups of children and adults. The main danger is the carriers of viral hepatitis B with close communication in these groups.
Vertical transmission of the pathogen is also possible. Infection usually occurs during labor, but infection of the fetus is possible in the uterus when the placenta is ruptured. The risk of transmission increases tenfold if a woman has not only HBsAg, but also HBeAg. If you do not carry out special preventive measures, viral hepatitis B is infected with up to 90% of children born to mothers with virus carriers.
The proportion of natural pathways of infection is 30-35% and tends to increase. A serious danger is the spread of viral hepatitis B in groups with around-the-clock stay of children: in children’s homes, orphanages, boarding schools. These children, as a rule, have a burdened history and often undergo parenteral therapeutic and diagnostic procedures. The threat of infection with viral hepatitis B also exists for the health workers of children’s homes who take care of children.
Natural susceptibility is high. It is known that transfusion of blood containing HBsAg leads to the development of hepatitis in 50-90% of recipients, depending on the infection dose. Post-infectious immunity is long lasting, possibly lifelong. Repeated cases of disease are observed only rarely.
The main epidemiological signs of viral hepatitis B. Viral hepatitis B is one of the ubiquitous infectious diseases. It is believed that about 2 billion people are infected with the virus, about 2 million patients die every year. The annual economic damage caused by the incidence of viral hepatitis B in Ukraine and the CIS countries is about $ 100 million. In the later stages of the disease there is a threat of the development of a tumor and cirrhosis of the liver, especially in those infected in childhood. In some countries, the virus of viral hepatitis B is responsible for 80% of all cases of primary hepatocellular carcinoma. Viral hepatitis B accounts for about half of all clinical hepatitis, and the death rate from acute viral hepatitis B is about 1%.
The incidence of hepatitis B is associated mainly with poor social and economic living conditions. The whole world can be divided into regions with high, intermediate and low endemicity. Among “healthy” carriers, a significant percentage of undetected asymptomatic forms of infection. There is every reason to believe that the ongoing epidemic process in viral hepatitis B is hidden in terms of its intensity and growth rates of indicators than manifest.
The young working-age population is intensively involved in the epidemic process: among the diseased, there is a predominance of people aged 15 to 30 years old, who account for about 90% of the diseased. Such age composition of patients with hepatitis is due to the fact that the structure of infection paths is dominated by “drug-addicted” and sexual transmission of infection. Young people under the age of 30 who used drugs account for 80% of those who died from hepatitis B. A significant proportion of deaths (up to 42%) is caused by simultaneous infection with viral hepatitis B, viral hepatitis C and viral hepatitis D. Currently in our country The problem of parenteral hepatitis is essentially transforming from a medical problem into a social one.
Persons who underwent blood transfusions and other medical parenteral manipulations prevail among the patients. Risk groups are medical workers who, in the course of their professional activities, come into contact with blood and its drugs (surgeons, dentists, hemodialysis workers, laboratories, etc.), as well as drug addicts (especially in recent years) when using a single syringe and sexually infected with each other. by. The familial nature of the incidence is characteristic, where the sexual and contact pathways of infection are actively realized. In various regions of the world, various main ways of spreading the infection prevail. In highly developed countries with initially favorable epidemic conditions, more than 50% of new cases of viral hepatitis B are due to sexual transmission of infection. Adolescents and young people, due to their active sexual life, constitute a group of particularly high risk of contracting viral hepatitis B. In regions with low endemicity, infection by the parenteral or transdermal route is of great importance in the transmission of the virus of hepatitis B. In regions with high endemicity, the most common route of infection is perinatal infection of the child from the mother. Approximately 5-17% of pregnant women are carriers of the virus of hepatitis B.
Pathogenesis During Viral Hepatitis B
The virus enters the human body through damaged skin or mucous membranes, then hematogenously disseminates into the liver, where it is fixed on hepatocytes due to surface receptors containing HBsAg. The expression of HBsAg occurs on the membrane of hepatic cells. In this case, the pathogen has no direct cytopathic effect on the liver cells.
The process of reproduction in hepatocytes is due to the activity of DNA polymerase, which is actively involved in the “completion” of the defective chain of viral DNA due to histocompatibility antigens common to various cells of the host organism. Daughter populations accumulate in the surface membrane of hepatocytes.
The cytolysis of hepatic cells occurs under the action of cytotoxic immune mechanisms. The targets for the latter are antigenic determinants of the viral hepatitis B virus associated with antigens of the major histocompatibility complex (HLA) on the surface of hepatocytes.
A significant role in the pathogenesis of viral hepatitis B is played by immune complexes (HBsAg antibodies), which settle on the vascular endothelium of various organs and lymph nodes, causing extrahepatic lesions (for example, glomerulonephritis and periarteritis nodosa).
Autoimmune reactions also occur in response to exposure to hepatocyte fragments after their death. This leads not only to the elimination of these fragments, but also to damage to healthy liver cells.
Morphological changes are characterized by dystrophic and necrobiotic processes in the centrolobular and periportal zones of the hepatic lobe with the subsequent development of fibrosis. At the same time, intrahepatic bile ducts are involved in the process, which leads to the formation of cholestasis.
Symptoms of Viral Hepatitis B
Incubation period. In the acute cyclic form of viral hepatitis B, its duration is subject to large fluctuations and varies from 30 to 180 days or more.
Dozheltushny period. It can occur in the same variants as in viral hepatitis B, but arthralgic, asthenovegetative and dyspeptic variants are more common. In the dyspeptic variant, persistent anorexia, persistent nausea, and intermittent vomiting without any apparent reason are expressed. It should be noted that with an influenza-like variant of the dozheltushny period with viral hepatitis B, catarrhal phenomena are not typical, and only in a small proportion of patients can an increase in body temperature be observed. However, patients often complain of joint pain; at the same time outwardly joints, as a rule, do not change. Arthralgia more often occurs at night and in the morning, and during movements in the joints disappear for a while. They may be accompanied by rash on the skin of the urticaria type. The combination of arthralgia and exanthema usually foreshadows a more severe course of the disease. In such cases, the clinical picture is complemented by an increase in body temperature, sometimes to high numbers.
Already in the dozheltushny period, dizziness, persistent drowsiness and manifestations of hemorrhagic syndrome in the form of bleeding from the nose and gums can be observed.
Icteric period. The state of health of patients, as a rule, does not improve, and in most cases worsens. Arthralgia and exanthema disappear, but dyspeptic symptoms increase.
Ictericism of the skin and mucous membranes slowly progresses, reaching its maximum not earlier than the 7-10th day from the moment of its appearance. Jaundice is usually intense, accompanied by pruritus. Hemorrhages in the form of petechiae or large bruises are often detected on the skin. With a more severe course, nosebleeds, bleeding of the gums are noted, and in women – an early arrival of heavy menstruation. Urine acquires a dark color, in the majority of patients the feces are aolitic.
The liver usually grows in size; it is clearly painful on palpation, quite soft in consistency. It is necessary to pay attention to the fact that, against the background of intense jaundice, the liver often does not increase, indicating a more severe course of hepatitis. In 50-60% of cases, splenomegaly is observed. The pulse is shortened, however, with more severe flow, tachycardia can be observed. Muffled heart sounds, note a slight hypotension. Patients are usually apathetic, experience dizziness, sleep disorders.
The course of the icteric period is long, delayed up to 1 month or more.
The recovery period begins from the moment the complex of dyspeptic symptoms diminishes or disappears, after which a slow decrease in bilirubinemia occurs. As for the change in the size of the liver, this process is sometimes delayed for several months.
When joining the cholestatic component (5-15% of patients), the disease acquires a torpid course. In these cases, unexpressed intoxication, prolonged cholestatic manifestations (high “monotonous” indicators of bilirubinemia and fermentemia, dark urine, acholitic stools, enlarged, non-contracting liver, subfebrile condition) are characteristic.
In addition to the acute cyclic form of the disease, viral hepatitis B can manifest itself as a chronic form (chronic in 5-10% of cases) and cirrhosis of viral etiology.
Complications of viral hepatitis B
The most serious and serious complication in terms of prognosis is acute hepatic encephalopathy (hepatic coma). It develops during massive cytolysis of hepatocytes and is characterized by deep depression of liver function, progressive neuropsychiatric symptoms and severe hemorrhagic manifestations. In its clinical development, acute hepatic encephalopathy goes through three successive stages.
Stage I (precoma I). Characterized by a sharp deterioration in the patient’s condition, increased jaundice and dyspeptic syndrome (nausea, repeated vomiting), the development of hemorrhagic manifestations, the appearance of liver odor from the mouth. Orientation in time and space, coordination of precise movements (paltsenosovaya and writing samples) are violated. Characteristic are slow thinking, sleep disturbances (drowsiness during the day and sleeplessness at night), dizziness, and a feeling of “dips” (feeling of falling into the abyss when closing eyes). Emotional instability attracts attention – apathy, lethargy, anxiety, anguish, alternating excitement, euphoria. There may be pain in the liver, fever. Bradycardia or normocardia is replaced by tachycardia. In patients with portocaval insufficiency, transient disorders of consciousness are noted.
Stage II (precoma II). A deeper disturbance of consciousness is characteristic; it is often confused. Patients are disoriented in time and space, euphoric or aggressive; excitement short-term and is replaced by apathy, intoxication amplifies. There is a tremor of the hands and the tip of the tongue, hemorrhagic syndrome increases. The liver is reduced in size and may become unavailable for palpation. Tachycardia increases, blood pressure tends to decrease. The edematous-ascitic syndrome develops. The duration of both stages of precoma is from several hours to several days.
Stage III (coma). Differs in loss of consciousness and at the beginning is shallow. Patients react with a moan to strong stimuli (for example, liver palpation). The swallowing and corneal reflexes are preserved. There are pathological reflexes, involuntary urination and defecation. With a deep coma comes reflexion, the reaction to any stimuli is lost. Patients die with symptoms of acute cardiovascular failure.
Already in the initial stages of the development of acute hepatic encephalopathy, the prothrombin index values progressively decrease, which is of great importance for assessing the severity of this condition.
Severe fulminant (fulminant) course of viral hepatitis B is more often noted in young patients, especially with mixed infections (a combination of viral hepatitis B + viral hepatitis D or viral hepatitis B + viral hepatitis C). The rapid and early development of acute hepatic encephalopathy with a high percentage (up to 90%) of deaths is characteristic.
Acute hepatic encephalopathy is characterized by the addition of a secondary infection with the development of sepsis, progressive deterioration of kidney function with a decrease in renal blood flow and glomerular filtration rate, a decrease in sodium concentration in the urine, an increase in its density, a decrease in diuresis.
Diagnosis of Viral Hepatitis B
Differential diagnosis of hepatitis B is carried out with the same infections as with hepatitis A. Unlike hepatitis A, hepatitis B is more severe with severe symptoms of intoxication, intense jaundice and often with hemorrhagic manifestations (subcutaneous hemorrhages, nasal bleeding). A great help in the differential diagnosis have indications that the patient during the last 6 months endured interventions with damage to the skin and mucous membranes or had sex with people who have had hepatitis B. The final etiological diagnosis is established using ELISA and PCR reactions.
Laboratory diagnosis
At the height of the disease, serum HBsAg, HBeAg or HBcIgM are detected by ELISA, RIA, in the early recovery period – HBcIgG, HBeIgG, in the recovery stage – HBslgG and HBcIgG. For verification of the pathogen, PCR is becoming increasingly important, revealing viral DNA, which determines the degree of virus replication activity.
In the dynamics of the disease, it is necessary to repeat these studies often enough to monitor the functional activity of the liver. Of particular importance in this regard is the determination of the prothrombin index, the reduction of which is less than 40% indicates a serious and sometimes critical condition of the patient.
Certain data indicating violations of the structure of the liver, gives ultrasound.
Treatment of Viral Hepatitis B
Patients with acute cyclical course of viral hepatitis B are hospitalized. In mild and moderate cases, treatment is similar to that in viral hepatitis A. In severe cases, prednisolone is prescribed 40-60 mg / day. Reducing the dose produced gradually since the relief of symptoms of intoxication. At the same time, patients are intensified by detoxification therapy (crystalloids and reopolyglukine in a 1: 3 ratio), correction of water-electrolyte imbalance (panangin, asparkam during hypokalemia) is carried out, lactulose (normozu), spasmolytic drugs (no-spa, eufillin) are prescribed low intestinal resorption (neomycin). In cases of marked cholestasis, ursodeoxycholic acid preparations (urosan, ursofalk) are recommended. With the development of acute hepatic encephalopathy, glucocorticoids are prescribed (intravenously 240–480 mg or more of prednisolone per day), although their effectiveness is questionable.
Prevention of Viral Hepatitis B
In the complex of preventive measures, measures aimed at preventing infections with viral hepatitis B during blood transfusions and carrying out therapeutic and diagnostic parenteral manipulations are of paramount importance. All donors are subjected to a comprehensive clinical and laboratory examination for the presence of hepatitis B antigens. Donors are excluded from persons who have had viral hepatitis B, regardless of the statute of limitations, as well as communicating with patients during the last 6 months. Persons suffering from chronic hepatitis (including unclear etiology) and who have been transfused in recent years are not allowed to donate blood. The introduction of autohemotransfusions is promising when the patient is given a blood transfusion prepared before the planned operation. Non-specific prophylaxis of hepatitis B is carried out with the use of disposable instruments during manipulations associated with damage to the skin and mucous membranes, careful sterilization of medical instruments, as well as strict control of the detection of viral antigens in donors. Of paramount importance is the widespread introduction and improvement of centralized sterilization of medical products. Interrupting the natural transmission of viral hepatitis B provides sanitary and hygienic measures: individualization of all personal hygiene items and their separate storage (shaving devices, toothbrushes, scouring pads, hairbrushes, etc.), compliance with personal hygiene rules, prevention of microtraumas in everyday life and at work . For the prevention of sexual transmission of the infection should avoid casual sex, use mechanical contraceptives. Prevention of occupational infections in health care facilities is achieved by strict compliance with the rules of the anti-epidemic regime, especially in hemodialysis, surgical, laboratory and other departments, in which staff often have contact with blood. When performing any parenteral interventions and procedures, rubber gloves are required.
Given the variety of ways of transmission of viral hepatitis B and a large number of sources of infection, the most promising means of prevention is vaccination. That it is the only means of preventing hepatitis B in newborns. This is the first vaccine that prevents cancer of the liver and reduces the carrier level of the virus in the population. WHO, having compiled many years of experience in the use of hepatitis B vaccine, recommends the introduction of vaccination into national vaccination calendars, regardless of the level of HBsAr carrier, as the most effective measure of specific prevention of this infection. Today, there is every reason to attribute hepatitis B to infections controlled by specific prophylaxis.
Over the past decade, more than 100 million people have been vaccinated in the world, which in a number of countries not only drastically reduced the incidence of hepatitis B and significantly affected the carrier rate in the population, but also made it legitimate to raise the issue of complete eradication of hepatitis B in these countries. More than 75 countries have included routine immunization against hepatitis B in newborns and / or adolescents in their vaccination programs. Currently, in many countries in Europe and America, they carry out a combined vaccination against hepatitis B as part of an expanded program of immunization of children. Specific prevention of hepatitis B is carried out by using one of the vaccines: HBVax-II (USA), Endzheriks-B (Belgium), Rec-HbsAg (Cuba), Evuks B (South Korea) and Combiotech (Russia).
All hepatitis B vaccines are interchangeable. Any of these can be used to complete a course of primary immunization initiated by another vaccine. The vaccine is administered intramuscularly, in children and adults – in the region of the deltoid muscle, in newborns and young children – in the anterolateral surface of the thigh. When combined with other parenteral vaccines, it is injected with a separate syringe into another area. Vaccines induce the formation of specific antibodies to HBsAr. An anti-HBsAT titer of 10 IU / L is sufficient to create immunity to viral hepatitis B. Achieving this level of antibodies after primary immunization leads to the formation of long-term immunological memory and provides long-lasting protection against hepatitis B even with a further drop in antibody levels. at least 5 to 12 years, regardless of the level of serum antibodies before re-administering antigens.
Vaccinations are subject to medical workers from high-risk groups for infection with viral hepatitis B, graduates of medical universities and technical schools, newborns born to mothers of HBsAr and women who had hepatitis B in the third trimester of pregnancy, children and staff of orphanages and special internaty, patients who are in offices with a high risk of infection with hepatitis B, persons in contact with patients with hepatitis B in the outbreaks of the disease at the place of residence. The calendar of Ukraine provides for routine vaccinations for children of the first year of life according to the scheme: newborns (in the first 12 hours of life), 1 month, 6 months. At the age of 13, children who have not previously been vaccinated against hepatitis B according to the scheme of 0-1-6 months are vaccinated. Children born to mothers, carriers of hepatitis B virus, or patients with viral hepatitis B in the third trimester of pregnancy, are vaccinated against hepatitis B according to the scheme of 0-1-2-12 months. Vaccinations at any age are subject to: children and adults in whose families there is a carrier of HbsAg or a patient with chronic hepatitis B; children of children’s homes, orphanages and boarding schools; children and adults who regularly receive blood and its preparations, as well as those who are on hemodialysis and hematologic patients; persons who have come into contact with material infected with the hepatitis B virus; medical professionals who have contact with the blood of patients; persons engaged in the production of immunobiological preparations from donor and placental blood; students of medical institutes and students of secondary medical schools (first of all graduates); injecting drug users.
Currently, it is assumed that the duration of post-vaccination immunity is approximately 15 years. Accumulated experience shows that vaccination leads to a decrease in the incidence of 10-12 times and HBSAg carriers in the population from 9-12% to 1%.
More than half of all cases of illness among health care workers account for the first five years from the start of work, and most of them – with an experience of one to five years. This indicates the need for compulsory vaccination against hepatitis B of health workers before the start of their professional activities.
However, immunization of only risk groups (health workers with blood contacts, newborns from carriers and patients, staff and children in children’s homes) does not effectively reduce the incidence. Actively influencing the epidemic process and achieving a significant reduction in the incidence of hepatitis B is only possible by moving from vaccination only those at risk to immunization of adolescents and newborns.
It is necessary to note the priority of this infection in terms of its economic significance, determined by the combination of a very high “cost” of one acute case of the disease (second only to polio and tetanus) and a wide and increasing spread among the population.