Hepatitis A - symptoms. Complications of viral hepatitis A

Viral hepatitis – group viral diseases humans, affecting the liver and manifested by enlarged liver, spleen, jaundice and intoxication. Chronic hepatitis (diffuse inflammatory processes in the liver that last more than six months) are also of a non-viral nature.

Among infectious diseases, viral hepatitis ranks second in number of people affected, after influenza.

Causative agents of viral hepatitis:

• hepatitis A virus;
• hepatitis B virus;
• hepatitis C virus;
• hepatitis D virus;
• hepatitis E virus;
• hepatitis F virus;
• hepatitis G virus.

Signs that unite viral hepatitis into a single group:

1. All viral hepatitis is transmitted from person to person.
2. The main routes of infection are through the blood and the gastrointestinal tract.
3. All pathogens are viruses that are quite stable in the environment.
4. The main target organ for all viruses is the liver.
5. The basis of the disease is the destruction of liver cells - hepatocytes.
6. All viral hepatitis have similar changes in many biochemical parameters, their dynamics.
7. The principles of treatment are similar for all viral hepatitis.

Classification of viral hepatitis

According to the duration of the process, viral hepatitis is:

• acute – up to 3 months (hepatitis A);
• protracted – up to 6 months (hepatitis B, C);
• chronic – over 6 months (hepatitis B, C, D).

By severity clinical manifestations highlight:

• Asymptomatic forms (carriage of the virus is typical for hepatitis B, C, subclinical form can occur with any hepatitis).
• Manifest forms (may be icteric or anicteric).

The course and symptoms of viral hepatitis of various forms

Viral hepatitis is characterized by a cyclic and acyclic (with exacerbations) course.

Subclinical forms are detected by chance - during examination of donors, persons in contact with patients with viral hepatitis, during medical examination. Such patients have no complaints or jaundice. However, the examination reveals an enlargement of the liver and spleen, and an increase in the activity of liver enzymes. The diagnosis can be confirmed using markers of viral hepatitis. The danger of subclinical forms is the possibility of the process transitioning into a chronic form.

The main periods of the disease with a cyclic course:

• incubation;
• preicteric;
• icteric;
• recovery.

The length of the incubation period depends on the specific virus, the infecting dose and the reactivity of the body.

Options for the course of the pre-icteric period:

• The asthenovegetative variant is characteristic of all viral hepatitis. He appears increased fatigue, decreased performance, weakness, and sometimes sleep disturbances.
• The dyspeptic (abdominal) variant occurs in all viral hepatitis. Its main symptoms are loss of appetite, a feeling of heaviness in the epigastric region, bloating, constipation or diarrhea.
• The arthralgic variant occurs with viral hepatitis B, C, D. It manifests itself as pain in large joints, but the configuration of the joints and the color of the skin over them remain unchanged.
• The pseudo-influenza variant is characteristic of viral hepatitis A and E. Catarrhal syndrome is absent in most cases, but aches throughout the body, fever, and headache appear.
• The allergic variant most often occurs with viral hepatitis B, C, D. It is accompanied by skin rashes, skin itching and increased body temperature.

In most cases, a mixed version of the course of the pre-icteric period occurs.

In the icteric period there are:

• The period of increase in clinical manifestations (intoxication, jaundice).
• The height of the illness; this period ends with a urinary crisis - at the height of jaundice, the amount of urine increases, it becomes light, and the jaundice decreases.
• The period of subsidence of jaundice.

Jaundice appears when the bilirubin level is 1.5 times or more higher than normal. First the urine darkens. Then a slight yellowness of the sclera appears. And the last thing to acquire a yellow tint is the skin.

The more intense the jaundice, the more severe the patient’s condition and the more pronounced the intoxication.

The recovery period is the time from the beginning of recovery, the elimination of all clinical symptoms and until all biochemical parameters are completely normalized.

Diagnosis of viral hepatitis

A general blood test indicates the presence of an inflammatory process: the number of leukocytes may increase, a shift in the leukocyte formula to the left may appear, and the ESR may accelerate.

In a general urine test in the pre-icteric period, an increase in the level of bile pigments and urobilin is determined. With the development of jaundice, the urine becomes dark color due to direct bilirubin, and urobilin disappears.

At the height of the disease, stool becomes grayish in color, since it lacks stercobilin, which colors stool brown.

When assessing cytolytic syndrome (liver destruction), the activity of the enzymes alanine aminotransferase (ALAT), aspartate aminotransferase (AST), glutamyl dehydrogenase (GlDH) and lactate dehydrogenase (LDH) is determined.

A violation of the synthetic function of the liver is indicated by a decrease in the level of total protein, the level of prothrombin, fibrinogen, and an increase in prothrombin time.

An increase in cholesterol levels indicates the presence of cholestasis (stagnation of bile).

With viral hepatitis, the level of bilirubin increases, mainly due to direct (bound) bilirubin.

From instrumental methods Ultrasound is widely used for differential diagnosis of viral hepatitis with other clinically similar diseases of the liver, pancreas, and biliary tract.

Specific diagnosis of viral hepatitis consists in identifying antibodies and virus particles that cause specific viral hepatitis.

Currently, 7 etiologically independent hepatitis have been identified, which are designated by the letters of the Latin alphabet: A, B, D, E, C, F, G. This does not exhaust the variety of viral liver lesions in humans. The antigenic heterogeneity of the viruses that cause hepatitis C and E has been proven, and it is possible to predict in the near future the identification of new etiologically independent forms of the disease.

HEPATITIS A

Hepatitis A (B 15) is an acute cyclical disease caused by an RNA virus; characterized short-term symptoms intoxication, quickly passing disorders of liver function. The course is benign. According to ICD-10, acute hepatitis A (B 15), hepatitis A with hepatic coma (B 15.0) and hepatitis A without hepatic coma(B 15.9).

Etiology. Hepatitis A virus (HAV) was discovered by S. Feinstone and co-workers (1970). It is a spherical RNA-containing particle with a diameter of 27-30 nm. By physical and chemical properties HAV belongs to enteroviruses with serial number 72 and is localized in the cytoplasm of hepatocytes. The virus is insensitive to ether, but is quickly inactivated by a solution of formaldehyde, chloramine and ultraviolet rays; at a temperature of 85°C it is inactivated within 1 minute.

The possibility of virus reproduction in primary and continuous monolayer lines of human and monkey cell cultures has been demonstrated, which opens up a source of reagents for the production of diagnostics, as well as for the design of vaccine preparations.

Epidemiology. Hepatitis A - common infection in childhood. The incidence can be sporadic or in the form of epidemic outbreaks.

IN general structure The incidence of hepatitis A in children accounts for more than 60%. Children aged 3-7 years are most often affected. Children of the 1st year of life practically do not get sick due to transplacental immunity received from the mother.

Hepatitis A is a typical anthroponotic infection. Sources of infection are only people with obvious or erased forms diseases, as well as virus carriers - healthy or convalescents. The main role in the active maintenance of the epidemic process is played by patients, especially with atypical forms. Often their disease remains unrecognized; they treat active image life, visit organized children's groups and become hidden and often powerful sources of infection.

In patients, the virus is contained in the blood, feces and urine. The virus appears in feces long before the first clinical symptoms, but its highest concentration occurs in the pre-icteric period. In the first days of the jaundice period, the virus can be detected in the blood and feces of no more than 10-15% of patients, and after the 4-5th day from the onset of jaundice - only in isolated cases.

Hepatitis A is a typical intestinal infection. The virus is transmitted mainly through contact and household contact, through hands contaminated with feces, as well as from food products And drinking water. Airborne transmission has not been confirmed. The role of flies as a transmission factor has been exaggerated. Transmission of infection parenterally occurs only when the patient’s blood containing the virus enters the recipient’s bloodstream. This is theoretically possible, but in practice it is, apparently, extremely rare due to the instability of the virus in the blood. All researchers exclude transplacental transmission of the virus from mother to fetus.

Susceptibility to the virus is extremely high. Antibodies to the hepatitis A virus are found in 70-80% and even 100% of adults.

The incidence of hepatitis A has seasonal increases and periodicity. The highest incidence is recorded in the autumn-winter period (September - January), the lowest in the summer (July - August). Epidemic outbreaks are usually observed in child care institutions.

After hepatitis A, persistent lifelong immunity is formed.

Pathogenesis. In hepatitis A, a direct cytopathic effect of the virus on the liver parenchyma is allowed. Taking this into account, the pathogenesis of the disease can be presented as follows. The virus enters the stomach with saliva, food or water, and then into small intestine, where, apparently, it is absorbed into the portal bloodstream and, through a related receptor, penetrates hepatocytes and interacts with biological macromolecules involved in detoxification processes. The consequence of this interaction is the release of free radicals, which act as initiators of lipid peroxidation processes in cell membranes. Increased peroxidation processes lead to changes structural organization lipid components of membranes due to the formation of hydroperoxide groups, which causes the appearance of “holes” in the hydrophobic barrier biological membranes and, therefore, increases their permeability. The central link in the pathogenesis of hepatitis A appears - cytolysis syndrome. Movement occurs biologically active substances along the concentration gradient. In the blood serum, the activity of hepatocellular enzymes with cytoplasmic, mitochondrial, lysosomal and other localization increases, which indirectly indicates a decrease in their content in intracellular structures, and, consequently, a reduced bioenergetic regime chemical transformations. All types of metabolism are disrupted (protein, fat, carbohydrate, pigment, etc.), resulting in a deficiency of energy-rich compounds and the bioenergetic potential of hepatocytes decreases. The ability to synthesize albumin, blood clotting factors, various vitamins is impaired, the use of glucose, amino acids for protein synthesis, complex protein complexes, and biologically active compounds is impaired; the processes of transamination and deamination of amino acids slow down, difficulties arise in the excretion of conjugated bilirubin, esterification of cholesterol and glucuronidation of many other compounds, which indicates sharp violation detoxifying function of the liver.

In the convalescence phase, protective factors and reparative processes are strengthened with complete fixation of the virus and complete restoration of the functional state of the liver. Most children recover within 1.5 to 3 months from the onset of the disease. For only some (3-5%) the initial protective factors may be insufficient; Relatively long-term (from 3 to 6-8 months or more) replicative activity of the virus in hepatocytes is maintained with disruption of their structure and function. In such cases, the course of the disease becomes protracted with complex mechanism structural and functional changes. However, even in these children, the defense mechanisms ultimately prevail - viral activity is blocked and recovery occurs. Chronic process As a result, hepatitis A is not formed.

Pathomorphology. The morphology of hepatitis A was studied based on data from intravital liver puncture biopsies. Changes are noted in all its tissue components: parenchyma, connective stroma, reticuloedothelium, biliary tract. The degree of organ damage can vary from slightly expressed dystrophic and necrotic changes in epithelial tissue lobules in mild forms to more widespread focal necrosis of the liver parenchyma in moderate and severe forms. There is no widespread necrosis of the liver parenchyma, and especially massive necrosis of the liver with hepatitis A.

Clinical manifestations. In the typical course of the disease, a cyclicity is clearly expressed with a successive change of 5 periods: incubation, initial or prodromal (pre-icteric), peak (icteric), post-icteric and the period of convalescence.

Incubation period with hepatitis A it lasts from 10 to 45 days, usually 15-30 days. During this period, there are no clinical manifestations of the disease, but viral antigen can already be detected in the blood and high activity hepatocellular enzymes (AlAT, AST, F-1-FA, etc.).

Initial (prodromal) period. The disease in most children begins acutely, with a rise in body temperature to 38-39°C and the appearance of symptoms of intoxication: malaise, weakness, headaches, loss of appetite, nausea and vomiting. Pain occurs in the right hypochondrium, in the epigastrium, or without a specific localization.

Children become capricious, irritable, lose interest in games and studies, and have trouble sleeping. Transient dyspeptic disorders often occur: flatulence, constipation, and less commonly, diarrhea.

After 1-2, less often after 3 days from the onset of the disease, the body temperature normalizes and the symptoms of intoxication weaken somewhat, but general weakness, anorexia, and nausea remain.

The most important objective symptoms in this period of the disease are enlargement of the liver, its sensitivity and pain on palpation.

In isolated cases, the spleen is palpable. By the end of the pre-icteric period, partial discoloration of feces (clay color) is observed.

In some children, the clinical manifestations of the initial period are mild or absent altogether; the disease begins immediately with a change in the color of urine and feces (see Fig. 73, 74 on the color insert). This onset of hepatitis usually occurs in mild and mild forms of the disease.

The duration of the prodromal (pre-icteric) period for hepatitis A is 3-8 days, on average 6±2 days, rarely it extends to 9-12 days or shortens to 1-2 days.

The height of the period (icteric period). The transition to the 3rd period usually occurs with a clear improvement in the general condition and a decrease in complaints. With the onset of jaundice general state in half of the patients it can be regarded as satisfactory, in the other half - as moderate for another 2-3 days of the icteric period. First, yellowness of the sclera appears, and then - the skin of the face, body, hard and soft palate, later - limbs. Jaundice grows quickly, within 1-2 days; often the patient turns yellow as if “overnight.”

Jaundice in hepatitis A can be mild, moderate or intense and lasts 7-14, usually 9-13 days, the icteric coloration of the skin folds lasts the longest, ears and especially the sclera in the form of marginal icterus.

At the height of jaundice, the liver is maximally enlarged, its edge is compacted, rounded, and painful on palpation. The edge of the spleen is often palpated.

Changes in other organs with hepatitis A are mild. Only moderate bradycardia can be noted, a slight decrease blood pressure, weakening of heart sounds, impurity of the first tone or slight systolic murmur at the apex, slight accent of the second tone on pulmonary artery; There are short-term extrasystoles.

After reaching the maximum level (usually on the 7-10th day from the onset of the disease), jaundice begins to decrease. This is accompanied by the complete disappearance of intoxication symptoms, improved appetite, and a significant increase in diuresis (polyuria). Bile pigments disappear in the urine and urobilin bodies appear, and the feces become colored. With a cyclical course of the disease, the decline in clinical manifestations takes 7-10 days. After this the 4th begins, post-icteric period with a relatively slow decline in the liver. Children feel quite healthy, but in addition to an enlarged liver and, in rare cases, the spleen, their liver function tests remain pathologically altered.

5th, recovery period, or period of convalescence, in most children it is accompanied by normalization of liver size, restoration of its functions and a completely satisfactory condition. In some cases, children complain of rapid fatigue during physical activity and abdominal pain; sometimes there remains a slight enlargement of the liver, symptoms of dysproteinemia, episodic or constant slight increase in the activity of hepatic cellular enzymes. These symptoms occur in isolation or in various combinations. The convalescence period takes about 2-3 months.

Classification. Hepatitis A is classified by type, severity and course.

Typical include all cases with the appearance of icteric staining of the skin and visible mucous membranes. Based on severity, they are classified into mild, moderate and severe forms. Atypical cases (anicteric, erased, subclinical hepatitis) are not divided by severity, since they are always regarded as mild hepatitis.

The severity of the clinical form of the disease is determined by initial period, but not before the maximum clinical symptoms of viral hepatitis; At the same time, manifestations of the initial (pre-icteric) period are also taken into account.

When assessing severity, the severity of general intoxication, jaundice, as well as the results of biochemical studies are taken into account.

Light form. It occurs in half of the patients and is manifested by a short-term moderate increase in body temperature or low-grade fever, mild signs of intoxication, minor subjective complaints during the height of the disease, and moderate enlargement of the liver.

Blood serum content total bilirubin does not exceed 85 µmol/l (with a norm of up to 17 µmol/l), and free - 25 µmol/l (with a norm of 15 µmol/l), the value of the prothrombin index is on the border of normal, thymol test moderately increased, the activity of hepatocellular enzymes exceeds the norm by 5-10 times. The course of the disease is cyclical and benign. The duration of the icteric period is about 7-10 days. The size of the liver returns to normal on the 25-35th day. In 5% of children the disease takes a protracted course.

Moderate form. It occurs in 30% of patients and manifests itself with moderately severe symptoms of intoxication. The severity of jaundice ranges from moderate to significant. The liver is painful, its edge is dense, protrudes from under the costal arch by 2-5 cm. The spleen is often enlarged. The amount of urine is noticeably reduced. In the blood serum, the level of total bilirubin ranges from 85 to 200 µmol/l, including unconjugated (indirect) - up to 50 µmol/l. Reduced with great consistency prothrombin index(up to 60-70%). The activity of hepatocellular enzymes exceeds the norm by 10-15 times.

The course of the disease is smooth. Symptoms of intoxication persist until the 10-14th day of illness, jaundice - 2-3 weeks, on average 14±5 days. Liver function is completely restored on the 40-60th day of illness. A protracted course is observed in only 3% of children.

Severe form hepatitis A is rare, occurring in no more than 1-3% of patients. In this form, the phenomena of general intoxication and jaundice are clearly expressed. The symptoms of the initial (prodromal) period differ little from those in the moderate form of the disease (vomiting, lethargy, anorexia). However, with the appearance of jaundice, the symptoms of intoxication not only do not weaken, but may even intensify. Apathy, lethargy, anorexia, dizziness, repeated vomiting, bradycardia, nosebleeds, hemorrhagic rashes, and a significant decrease in diuresis are noted. The liver is sharply enlarged, its palpation is painful, the spleen is enlarged. The bilirubin content in the blood serum is more than 170-200 µmol/l, while unconjugated (indirect) bilirubin is more than 50 µmol/l, the prothrombin index is reduced to 50-60%, the activity of hepatocellular enzymes is increased 15-30 times.

Anicteric form. Throughout the entire disease, icterus of the skin and sclera is not observed during systematic monitoring of the patient. The remaining symptoms in the anicteric form correspond to those in the icteric form. A short-term increase in body temperature, loss of appetite, lethargy, weakness, nausea and even vomiting are possible, lasting no more than 3-5 days. The leading symptom of the anicteric form is acute enlargement of the liver with its hardening and pain on palpation. There is an enlargement of the spleen, dark urine and somewhat discolored stool. Always found in blood serum increased activity AlAT, AST, F-1-FA and other liver enzymes; the thymol test and the content of β-lipoproteins were increased. There is often a short-term increase in conjugated (direct) bilirubin by 1.5-2 times the norm.

The anicteric form occurs in approximately 20% of patients with verified hepatitis A.

At subclinical (inapparent) form There are completely no clinical manifestations. The diagnosis is established only by biochemical examination of children who are in contact with patients with viral hepatitis. The most significant for the diagnosis of such forms is an increase in enzyme activity (AlAT, AST, F-1-FA, etc.), less often - a positive thymol test. The diagnosis is reliably confirmed by the detection of IgM antibodies to HAV in the blood serum. There is reason to believe that in the focus of hepatitis A infection, most children carry inapparent forms, which, while remaining undetected, support the epidemic process.

At cholestatic form Symptoms come to the fore in the clinical picture obstructive jaundice. There is reason to believe that this form of the disease does not have clinical independence. Its development is based on bile retention at the level of the intrahepatic bile ducts. According to statistics, cholestasis syndrome with hepatitis A occurs rarely - in no more than 2% of patients and, as a rule, in girls in the prepubertal and pubertal periods.

The leading clinical symptom of hepatitis A with cholestatic syndrome is severe and prolonged (30-40 days or more) congestive jaundice and itching of the skin. Often the jaundice has a greenish or saffron tint, but sometimes it may be completely absent, then itching of the skin predominates. Symptoms of intoxication are not expressed, the liver is slightly enlarged, the urine is dark, the feces are discolored. In blood serum, the bilirubin content is usually high, exclusively due to the direct fraction. The activity of hepatocellular enzymes is within normal limits or slightly increased. There is an increased level of total cholesterol, β-lipoproteins, alkaline phosphatase. The course of hepatitis A with cholestatic syndrome, although long-term, is always favorable. Chronic hepatitis does not develop.

Flow. Hepatitis A can be acute and protracted, smooth without exacerbation, with exacerbations, as well as with complications from the biliary tract and the addition of intercurrent diseases.

Acute course observed in 95% of children with verified hepatitis A. When acute course There are cases with particularly rapid disappearance of clinical symptoms, when by the end of the 2-3rd week of the disease a complete clinical recovery occurs and the functional state of the liver is normalized. In children, the overall duration of the disease, although it fits within the time frame acute hepatitis(2-3 months), but within 6-8 weeks after the disappearance of jaundice, certain complaints may remain (appetite disturbance, discomfort in the liver, rarely - enlarged spleen, incomplete normalization of liver function, etc.). These cases can be considered as prolonged convalescence. The further course of the disease in these children is also benign. The formation of chronic hepatitis is not observed.

Protracted current accompanied by clinical, biochemical and morphological signs of active hepatitis lasting from 3 to 6 months or more. The initial manifestations of the disease in a prolonged course are practically no different from those in acute hepatitis. Violation of cyclicity is detected only in the post-icteric period. At the same time, the liver and sometimes the spleen remain enlarged for a long time. In the blood serum, the activity of hepatocellular enzymes does not show any tendency towards normalization. However, prolonged hepatitis A always ends in recovery.

The course is aggravated. Exacerbation is understood as an increase in clinical signs of hepatitis and deterioration in liver function tests against the background of persistent pathological process in the liver. Exacerbation should be distinguished from relapses - re-occurrence (after a period of absence of visible manifestations of the disease) of the main symptom complex in the form of an enlarged liver, spleen, the appearance of jaundice, a possible increase in body temperature, etc. Relapses can also occur in the form of an anicteric variant. Both exacerbations and relapses are always preceded by an increase in the activity of hepatocellular enzymes.

In all children with a “relapse” of hepatitis A, the addition of another hepatitis - B, C, etc. is usually determined. The main reason for the exacerbation is the activation of the virus in a child with a functional deficiency of the T-immune system of the hyposuppressor type, which results in incomplete elimination of infected hepatocytes and repeated breakthrough of the virus into free circulation with subsequent damage to new hepatocytes.

Course with damage to the bile ducts. In hepatitis A, damage to the biliary tract usually manifests itself as dyskinetic phenomena. hypertensive type. They occur in any form of hepatitis A, but are more pronounced in the moderate form, especially in patients with cholestatic syndrome. Clinically, damage to the biliary tract can manifest itself with all the symptoms characteristic of the cholestatic form of the disease, but often occurs without clear symptoms and is diagnosed based on the results of a laboratory test. In most children, dyskinetic disorders of the biliary tract resolve without any treatment, as the symptoms of hepatitis A disappear. The total duration of the disease in most cases falls within the framework of acute hepatitis.

Course with the addition of intercurrent infections. Intercurrent diseases usually do not have a significant effect on the severity of clinical manifestations, functional disorders, as well as the course, immediate and long-term outcomes of hepatitis A. In some patients, with the addition of an intercurrent infection, a slight enlargement of the liver, an increase in the activity of hepatocellular enzymes, and the thymol test are observed.

Exodus. As a result of hepatitis A, recovery with complete restoration of the liver structure is possible; recovery from anatomical defects (residual fibrosis) or formation various complications from the biliary tract and gastroduodenal zone.

Recovery with complete restoration of liver structure and function - the most common outcome of hepatitis A.

Residual fibrosis or recovery with anatomical defect (post-hepatitis hepatomegaly)- long-term or lifelong enlargement of the liver with complete absence clinical symptoms and changes in results laboratory research. The morphological basis of hepatomegaly is residual liver fibrosis in the complete absence dystrophic changes hepatocytes.

Biliary tract damage it is more correct to interpret it not as an outcome, but as a complication of hepatitis A as a result of activation of microbial flora.

Clinically, damage to the biliary tract is manifested by various complaints: pain in the right hypochondrium, nausea, vomiting. As a rule, complaints in children appear 2-3 months after hepatitis A. In most patients, combined gastroduodenal and hepatobiliary pathology is determined, often with an abnormal development of the gallbladder.

Diagnostics hepatitis A is based on clinical, epidemiological and laboratory data. Clinical signs can be considered supporting, epidemiological - suggestive, but the results laboratory methods have crucial at all stages of the disease.

Laboratory indicators are divided into specific and nonspecific. Specific are based on the detection of HAV RNA in the blood by PCR and specific anti-HAV IgM antibodies by ELISA. Determination of IgG class antibodies has diagnostic value only when the titer increases in the dynamics of the disease. In addition, testing for anti-HAV IgG may be important for assessing the immunostructure of the population, i.e. for broad epidemiological generalizations.

Non-specific methods play a decisive role in establishing the fact of liver damage, assessing the severity, course and prognosis of the disease. Among the numerous laboratory biochemical tests, the most effective are the determination of the activity of hepatic cellular enzymes (AlAT, AST, F-1 - FA, etc.), indicators of pigment metabolism and protein-synthesizing function of the liver.

Treatment Patients with hepatitis A are best treated at home. Restrictions in motor activity should depend on the severity of symptoms of intoxication, the patient’s well-being and the severity of the disease. With erased, anicteric and in most cases with mild forms, the regime can be semi-bed from the first days of the icteric period. For moderate and especially severe forms, it is prescribed bed rest during the entire period of intoxication - usually the first 3-5 days of the icteric period. As intoxication disappears, children are transferred to semi-bed rest. The criteria for expanding the regimen are improvement of well-being and appetite, reduction of jaundice.

Children are exempt from physical education for 3-6 months, and sports for 6-12 months. Increase physical activity must be individualized and fully consistent with the course of the pathological process, functional restoration of the liver, taking into account residual effects, age and premorbid background of the child.

Patients need a complete, high-calorie and, if possible, physiological diet with a ratio of proteins, fats and carbohydrates of 1:1:4-5.

Proteins are introduced into the diet in the form of cottage cheese, milk, kefir, low-fat varieties meat (beef, veal, chicken), low-fat fish (cod, pike perch, navaga, pike), omelet, low-fat cheese. Fats are given in the form of creamy and vegetable oil(corn, olive, sunflower). Carbohydrates are found in rice, semolina, oatmeal, buckwheat porridge, bread, pasta, sugar, and potatoes.

IN daily ration The child must be provided with a sufficient amount of raw and boiled vegetables (carrots, cabbage, cucumbers, tomatoes, zucchini), herbs, fruits, juices.

Extractive substances, refractory fats (lard, margarine, shortening), fatty sausages, pork, ham, canned meat, fat bird, fatty types fish, spicy sauces, marinades, legumes, spicy cheeses, garlic, radishes, radishes, chocolate, cakes, pastries, sweets, hot seasonings (mustard, pepper, mayonnaise), smoked meats, mushrooms, nuts, horseradish, etc.

Honey, jam, marshmallows, savory cookies, dried apricots, prunes, raisins, mousses, jellies, jelly, salads, vinaigrettes, soaked herring, jellied fish are allowed.

People with hepatitis A usually do not need medications, but it is still advisable to prescribe drugs with choleretic effect. In the acute period of the disease, it is better to use drugs with predominantly cholelytic action (magnesium sulfate, flamin, berberine, etc.), and in the period of convalescence - cholesecreting agents (allochol, cholenzyme, etc.). In case of hepatitis A, it is pathogenetically justified to prescribe a complex of B vitamins (B 1, B 3, B 6), as well as vitamins C and PP orally in the standard dose. During the period of convalescence and especially with prolonged hepatitis A, you can prescribe phosphogliv 1 capsule 3 times a day with meals for 2-4 weeks, Liv52 K (children from 2 years old) 10-20 drops 2 times a day 30 minutes before food, Liv52 in tablets (children from 6 years old) 1-2 tablets 2-3 times a day 30 minutes before meals for 2-4 weeks, or take a course of treatment with Legalon 1/2 -1 tablet ( 1/2 -1 spoon) 3 times a day for 2-3 weeks. Pathogenetically justified is the administration of a complex of vitamins A (B1, B3, B6), as well as vitamins C and PP orally in the standard dose.

In the cholestatic form, relief of cholestasis is achieved by prescribing the drug ursodeoxycholic acid (ursosan) at a dose of 10-15 mg/(kg day) for the entire period of clinical and laboratory manifestations plus 2-3 weeks to eliminate subclinical cholestasis.

In the period of early and late convalescence, especially with a protracted course of hepatitis A and significant severity of residual effects, taking into account the possibility of the formation of pathology of the biliary tract and gastroduodenal zone as a drug that can effectively influence these adverse consequences and complications, the prescription of Ursosan for a longer course (3-6 months) is pathogenetically justified. For the same purpose, during the period of convalescence, you can prescribe phosphogliv or essentiale, 1 capsule 3 times a day with meals for 2-4 weeks, or carry out a course of treatment with legalon. Infusion therapy prescribed for severe forms and for individual patients with moderate forms of the disease. A 1.5% solution of reamberin is injected intravenously at a rate of 10 ml/kg body weight reopolyglucin, hemodez, 10% glucose solution.

After the end of the acute period, all children are subject to mandatory dispensary observation. It is better to carry out clinical examination in a special room organized at the hospital. If it is impossible to organize such an office, medical examination should be carried out by a local pediatrician in a children's clinic.

The first examination and examination of the child is carried out on the 45-60th day from the onset of the disease, repeated - after 3 months. In the absence of residual effects, convalescents are removed from the register. If there are clinical or biochemical signs of incompleteness of the process, dispensary observation carried out until complete recovery.

Regardless of the form and severity of the disease, enterosorption therapy (enterosgel, enterodesis) must be prescribed for the entire duration of treatment. Enterosorbents bind toxic substances and metabolites in the gastrointestinal tract and interrupt their recycling processes. All this, of course, leads to a reduction in the metabolic and toxic load on liver cells and accelerates the repair processes of liver tissue.

Clinical examination of convalescents living in rural areas, is carried out at infectious diseases departments of central regional children's hospitals and in children's clinics.

Prevention. Measures to prevent the spread of hepatitis A infection involve influencing the source of infection, the routes of its transmission and the susceptibility of the body.

Neutralization of the source of infection is ensured early diagnosis of all cases of the disease and timely isolation of patients.

In all contact children, the skin and sclera are examined daily, and attention is paid to the size of the liver, the color of urine and feces.

In the focus of hepatitis A to identify atypical forms It is recommended to conduct a laboratory examination: determine the activity of ALT and anti-HAV IgM in blood serum (blood is taken from a finger). These studies should be repeated every 10-15 days until the outbreak ends. This makes it possible to identify almost all infected people and quickly localize the source of infection.

To suppress the transmission of infection, strict control over public catering, quality drinking water, maintaining public and personal hygiene.

When a patient with hepatitis A is identified, current and final disinfection is carried out at the source of infection.

To increase the immunity of the population to hepatitis A, the introduction of normal immunoglobulin is of particular importance. Timely use of immunoglobulin in the focus of hepatitis A helps stop the outbreak. For achievement preventive effect it is necessary to use immunoglobulin with a high content of antibodies to the hepatitis A virus - 1:10,000 or higher.

There is planned or pre-season immunoprophylaxis for hepatitis A and immunoprophylaxis for epidemic indications. Planned pre-season (August-September) prevention is carried out in regions with a high incidence of hepatitis A - more than 12 per 1000 children.

In areas with low incidence, immunoprophylaxis is carried out only for epidemic indications.

Titrated immunoglobulin is administered to children from 1 to 14 years of age, as well as to pregnant women who have had contact with people with hepatitis A in the family or children's institution within 7-10 days after the 1st case of illness. Children aged 1 to 10 years are administered 1 ml of 10% immunoglobulin, over 10 years and adults - 1.5 ml.

In children's institutions, with incomplete separation of groups, immunoglobulin is administered to all children who have not had hepatitis A. In case of complete separation (school classes), the issue of administering immunoglobulin to children of the entire institution should be decided individually.

Effective prevention of hepatitis A is possible only through universal vaccination. The following vaccines are registered and approved for use in Russia:

Vaccine against hepatitis A, purified concentrated adsorbed inactivated liquid GEP-A-in-VAK, Russia;

Vaccine against hepatitis A with polyoxidonium GEP-A-in-VAK-POL, Russia;

Havrix 1440 from Glaxo Smith Klein, England;

Havrix 720 from Glaxo Smith Klein, England;

Avaxim from Sanofi Pasteur, France;

Waqta 25 units (and 50 units). Merck Sharp and Dome, USA;

Twinrix is ​​a vaccine against hepatitis A and B from Glaxo Smith Klein, England.

It is recommended to start vaccination against hepatitis A at 12 months of age. The vaccine is administered intramuscularly twice according to the schedule: 0 and 6 months - 12 months. The hepatitis A vaccine can be administered simultaneously with the hepatitis B vaccine if the timing of vaccinations in different parts of the body coincides. A protective level of immunity is formed in 95% of vaccinated people.

Reactions to hepatitis A vaccine are relatively rare. Some children may experience pain, hyperemia and swelling at the injection site; they rarely occur. general reactions: increased body temperature, chills, allergic rash. In hypersensitized children, anaphylactic reactions are theoretically possible, which can be easily eliminated with generally accepted desensitizing drugs.

HEPATITIS E

Hepatitis E (B 17.2) is a widespread disease in many developing countries with hot climates.

Etiology. The causative agent of the disease is a virus-like spherical particle with a diameter of 27 nm. It has no antigenic similarity to HAV and is not considered a variant or subtype. The virus is found in the feces of individuals with a clinical picture of acute hepatitis, classified as “neither A, nor B” hepatitis, as well as in monkeys experimentally infected with this type of virus. Viral particles react with the sera of the same sick and experimental animals in the convalescent stage.

Epidemiology. The source of infection is a sick person who suffers a typical or atypical (anicteric, erased) form of the disease. Chronic carriage of the virus has not been described. The infection is transmitted through the fecal-oral route, mainly through contaminated water; transmission through food and household contact is possible. Seasonality coincides with the period of increased incidence of hepatitis A.

In the CIS countries, the largest number of diseases is recorded in Central Asia, mainly in the autumn-winter period.

The majority of cases are between 15 and 30 years of age, and only about 30% are children. It is possible that the relatively low incidence in children is explained by the predominance of erased and subclinical forms that are not diagnosed. Susceptibility to hepatitis E has not been precisely established; there is reason to consider it high. The lack of widespread spread of hepatitis E in our country is probably due to the predominance of the water mechanism of infection and the high infectious dose. There is an opinion that hepatitis E is a natural focal disease.

Pathogenesis. The mechanisms leading to liver damage in hepatitis E are not precisely known. One can only assume that they do not differ from those with hepatitis A. In an experiment on monkeys, it was shown that by the end of the month from the moment of their infection with a suspension of fecal extract from patients with hepatitis E, a picture of acute hepatitis was found in the liver of animals, accompanied by an increase in the level of transaminases; at the same time, virus-like particles appear in the feces, and after that, on the 8-15th day, antibodies to the virus are detected in the blood serum.

The morphological picture of the liver with hepatitis E is generally the same as with hepatitis A.

Clinical manifestations. The incubation period ranges from 10 to 50 days. The disease begins with the appearance of lethargy, weakness, loss of appetite; Possible nausea and repeated vomiting, abdominal pain. An increase in body temperature, unlike that with hepatitis A, is uncommon. The pre-icteric period lasts from 1 to 10 days. Usually the urine darkens on the 3-4th day from the onset of the disease. Jaundice appears and gradually increases over 2-3 days. With the appearance of jaundice, the symptoms of intoxication do not disappear (with hepatitis A they disappear). Patients still complain of weakness, poor appetite, pain in epigastric region and right hypochondrium. Sometimes there is itching of the skin and low-grade fever bodies. The liver is enlarged in all patients, the edge of the spleen is palpable only in isolated cases.

At the height of the disease in the blood serum, the content of total bilirubin is increased by 2-10 times, mainly due to the direct fraction, the activity of hepatocellular enzymes is increased by 5-10 times, the thymol test, unlike that in hepatitis A, remains within normal limits or increased by no more than 1.5-2 times, i.e., as with hepatitis B. A decrease in the mercuric acid test seems unusual, since it, as a rule, does not decrease in mild and moderate forms of hepatitis A and B.

The icteric period lasts 2-3 weeks. The size of the liver, the activity of enzymes and the protein-synthesizing function of the liver are gradually normalized.

Flow. The disease is usually acute. After 2-3 months from the onset of the disease, most children experience complete restoration of the structure and function of the liver. The protracted course is clinically no different from that of hepatitis A. In adults, especially often in pregnant women, malignant forms with fatal. In children, such forms apparently do not occur. The formation of chronic hepatitis has not been described.

Diagnostics. The diagnosis of hepatitis E is currently established based on the detection in the blood serum of antibodies to the hepatitis E virus of the IgM class in ELISA and viral RNA in PCR.

Treatment. Hepatitis E is treated in the same way as other viral hepatitis.

Prevention. When a case of hepatitis E appears, send emergency notice in SES. Patients are isolated for up to 30 days from the onset of the disease. In children's institutions, after isolating the patient, final disinfection is carried out, and the group is quarantined for 45 days. Contact children are subject to regular medical supervision Before the end of quarantine, those who have not had hepatitis E can be given immunoglobulin. However, the effectiveness of this measure requires further study. Obviously, it is effective only if commercial batches of immunoglobulin contain antibodies to the hepatitis E virus.

HEPATITIS B

Hepatitis B (B 16) is an acute or chronic liver disease caused by a DNA virus. Transmission of infection occurs parenterally. Hepatitis B occurs in various clinical and morphological variants: from “healthy” carriage to malignant forms, chronic hepatitis, liver cirrhosis and hepatocellular carcinoma.

According to ICD-10 there are:

B16.0 - acute hepatitis B with delta agent (co-infection) and hepatic coma;

B16.1 - acute hepatitis B with delta agent (co-infection) without hepatic coma;

B16.2 - acute hepatitis B without delta agent with hepatic coma;

B16.9 - acute hepatitis B without delta agent and without hepatic coma.

Etiology. The causative agent of the disease is a DNA-containing virus from the hepadnavirus family (from the Greek hepar - liver and English DNA - DNA).

Hepatitis B viruses (HBV), or Dane particles, are spherical formations with a diameter of 42 nm, consisting of an electron-dense core (nucleocapsid) with a diameter of 27 nm and an outer shell 7-8 nm thick. In the center of the nucleocapsid is the viral genome, represented by double-stranded DNA.

The virus contains 3 antigens that have vital importance for laboratory diagnosis of the disease: HBcAg - nuclear, core antigen of a protein nature; HBeAg - transformed HBcAg (infectiousness antigen); HBsAg is a surface (Australian) antigen that forms the outer shell of the Dane particle.

HBV is very resistant to high and low temperatures. At a temperature of 100° C, the virus dies in 2-10 minutes; at room temperature it lasts 3-6 months, in the refrigerator - 6-12 months, frozen - up to 20 years; in dried plasma - 25 years. The virus is extremely resistant to exposure chemical factors: 1-2% chloramine solution kills the virus after 2 hours, 1.5% formaldehyde solution - after 7 days. The virus is resistant to lyophilization, exposure to ether, ultraviolet rays, acids, etc. When autoclaving (120°C), the activity of the virus is completely suppressed only after 5 minutes, and when exposed to dry heat (160°C) - after 2 hours.

Epidemiology. Hepatitis B is an anthroponotic infection: the only source of infection is humans.

The main reservoir of the virus is “healthy” virus carriers; Patients with acute and chronic forms of the disease are less contagious.

Currently, according to incomplete data, there are about 300 million virus carriers in the world, including more than 5 million living in our country.

The prevalence of “healthy” carriage varies in different territories. There are territories with low (less than 1%) carriage of the virus in the population: the USA, Canada, Australia, Central and Northern Europe; medium (6-8%): Japan, Mediterranean countries, South-West Africa; high (20-50%): Tropical Africa, islands of Oceania, Southeast Asia, Taiwan.

In the CIS countries, the number of virus carriers also varies wide range. A large number of them are registered in Central Asia, Kazakhstan, Eastern Siberia, Moldova - about 10-15%; in Moscow, the Baltic states, Nizhny Novgorod - 1-2%.

In all people infected with HBV, regardless of the nature of the process (“healthy” carriers, patients with acute, chronic hepatitis), HBsAg - the main marker of infection - is found in almost all biological environments of the body: in blood, semen, saliva, urine, bile, tear fluid , breast milk, vaginal secretion, cerebrospinal fluid, synovial fluid. However, only blood, semen and saliva, where the concentration of the virus is significantly higher than the threshold, pose a real epidemic danger. The most dangerous is the blood of the patient and the virus carrier.

HBV is transmitted exclusively by the parenteral route: through the transfusion of infected blood or its preparations (plasma, red blood cells, albumin, protein, cryoprecipitate, antithrombin, etc.), the use of poorly sterilized syringes, needles, cutting instruments, as well as during scarification, tattoos, and surgical interventions. , dental treatment, endoscopic examination, duodenal intubation and other manipulations during which the integrity of the skin and mucous membranes is disrupted.

TO natural ways HBV transmission includes transmission of the virus through sexual contact and vertical transmission from mother to child. Sexual tract transmission should be considered parenteral, since infection occurs through inoculation of the virus through microtraumas of the skin and mucous membranes of the genitals.

Vertical transmission HBV is carried out mainly in regions with a high prevalence of virus carriage. A mother can infect her baby if she is a carrier of the virus or has hepatitis B, especially in the last trimester of pregnancy. Infection of the fetus can occur transplacentally, during childbirth or immediately after birth. Transplacental transmission occurs relatively rarely - no more than 10% of cases. The risk of infection increases sharply when HBeAg is detected in the mother’s blood, especially in high concentration(up to 95%).

Infection of children from mothers who are carriers of HBV occurs mainly during childbirth as a result of contamination from blood containing amniotic fluid through macerated skin and mucous membranes of the child. In rare cases, a child becomes infected immediately after birth through close contact with an infected mother. Transmission of infection in these cases occurs through microtrauma, i.e., parenterally, and possibly during breastfeeding. Infection of the child most likely occurs not through milk, but as a result of the contact of the mother’s blood (from cracked nipples) on the macerated mucous membranes of the child’s oral cavity.

When using all routes of transmission of infection, the risk of perinatal infection of a child from a mother with hepatitis B or a virus carrier can reach 40%. Most often, infection through close household contact occurs in the family, as well as in orphanages, boarding schools and other closed institutions. The spread of infection is facilitated by overcrowding, low sanitary and hygienic living standards, and poor communication culture. In close relatives (father, mother, brothers, sisters) of children with chronic hepatitis B, during the first study, markers of hepatitis B are detected in 40% of cases, and after 3-5 years - in 80%.

The population's susceptibility to the hepatitis B virus appears to be universal, but the outcome of a person's encounter with the virus usually results in asymptomatic infection. The frequency of atypical forms cannot be accurately counted, but judging by the identification of seropositive individuals, then for each case of manifest hepatitis B there are tens and even hundreds of subclinical forms.

As a result of hepatitis B, persistent lifelong immunity is formed. Recurrent disease unlikely.

Pathogenesis. In the mechanism of development of the pathological process in hepatitis B, several leading links can be distinguished:

Introduction of a pathogen - infection;

Fixation on the hepatocyte and penetration into the cell;

Reproduction and release of the virus onto the surface of the hepatocyte, as well as into the blood;

Inclusion of immune reactions aimed at eliminating the pathogen;

Damage to extrahepatic organs and systems;

Formation of immunity, release from the pathogen, recovery.

Since HBV infection always occurs through the parenteral route, the moment of infection is almost equivalent to the penetration of the virus into the blood.

The tropism of HBV to liver tissue is predetermined by the presence in HBsAg of a special receptor - a polypeptide with a molecular weight of 31,000 D (P31), which has albumin-binding activity. A similar zone of polyalbumin is also found on the membrane of human and chimpanzee liver hepatocytes, which essentially determines the tropism of HBV to the liver.

When a hepatocyte is infected, the process can develop along a replicative and integrative path. In the 1st case, there is a picture of acute or chronic hepatitis, and in the 2nd case - virus carriage.

The reasons that determine the interaction of viral DNA and hepatocytes have not been precisely established. Most likely, the type of response is genetically determined.

The final result of the replicative interaction is the assembly of cow antigen structures (in the nucleus) and the assembly of the complete virus (in the cytoplasm), followed by the presentation of the complete virus or its antigens on the membrane or in the membrane structure of hepatocytes.

In the future, the liver is necessarily included in the immunopathological process. The damage to hepatocytes is due to the fact that as a result of the expression of viral antigens in the membrane of hepatocytes and the release of viral antigens into free circulation, a chain of successive cellular and humoral immune reactions is activated, aimed at removing the virus from the body. This process is carried out in full accordance with the general patterns of the immune response during viral infections. To eliminate the pathogen, cellular cytotoxic reactions are activated, mediated by various classes of effector cells: K cells, T cells, natural killer cells, macrophages. During these reactions, the destruction of infected hepatocytes occurs, which is accompanied by the release of viral antigens (HBcAg, HBeAg, HBsAg), which trigger the antibody genesis system, as a result of which specific antibodies accumulate in the blood, primarily to the cow - anti-HBc and e-antigen - anti- NWe. Consequently, the process of releasing the liver cell from the virus occurs through its death as a result of cellular cytolysis reactions.

At the same time, specific antibodies accumulating in the blood bind virus antigens, forming immune complexes, which are phagocytosed by macrophages and excreted by the kidneys. In this case, various immune complex lesions may occur in the form of glomerulonephritis, arteritis, arthralgia, skin rashes etc. During these processes, the body of most patients is cleared of the pathogen and complete recovery occurs.

In accordance with the concept of the pathogenesis of hepatitis B, all the diversity clinical options The course of the disease is explained by the peculiarities of the interaction of the pathogen virus and the cooperation of immunocompetent cells, in other words, by the strength of the immune response to the presence of viral antigens.

In conditions of an adequate immune response to viral antigens, acute hepatitis develops with a cyclical course and complete recovery. With a decrease in the immune response, immune-mediated cytolysis is insignificantly expressed, so effective elimination of infected liver cells does not occur. This leads to mild clinical manifestations with long-term persistence of the virus and, possibly, to the development of chronic hepatitis. On the contrary, in the case of a genetically determined strong immune response and massive infection (blood transfusion), extensive areas of liver cell damage occur, which clinically correspond to severe and malignant forms of the disease.

Pathomorphology. Based on the characteristics of morphological changes, there are 3 variants of acute hepatitis B: cyclic, massive liver necrosis, cholestatic pericholangiolytic hepatitis.

At cyclic form of hepatitis B dystrophic, inflammatory and proliferative changes are more pronounced in the center of the lobules, and with hepatitis A they are localized along the periphery of the lobules, spreading to the center. These differences are explained in different ways penetration of the virus into the liver parenchyma. The hepatitis A virus enters the liver through portal vein and spreads to the center of the lobules, and HBV penetrates through the hepatic artery and the branches of the capillaries, which uniformly supply all the lobules down to their center.

Largest morphological changes in the parenchyma are observed at the height of clinical manifestations, which usually coincides with the 1st decade of the disease. During the 2nd and especially the 3rd decade, regeneration processes intensify. By this period, necrobiotic changes have almost completely disappeared and processes of cellular infiltration begin to predominate, with a slow subsequent restoration of the structure of the hepatocellular plates. However, complete restoration of the structure and function of the liver parenchyma occurs only after 3-6 months from the onset of the disease and not in all children.

At massive liver necrosis morphological changes are maximally expressed. Depending on the severity and prevalence, liver necrosis can be massive or submassive. With massive necrosis, almost the entire epithelium dies or a small border of cells remains along the periphery of the lobules. With submassive necrosis, the majority of hepatocytes are destroyed, mainly in the center of the lobules. Massive necrosis represents the peak of the changes that are characteristic viral hepatitis IN.

Cholestatic (pericholangiolytic) hepatitis - a special form of the disease in which the greatest morphological changes are found in the intrahepatic bile ducts; a picture of cholangiolitis and pericholangiolitis is observed. This is a relatively rare form in children and occurs almost exclusively in hepatitis B. In the cholestatic form, there is cholestasis with dilation of the bile capillaries with stasis of bile in them, with proliferation of cholangioles and cellular infiltrates around them. Liver cells are slightly affected in this form of hepatitis.

Clinical manifestations. In typical cases of the disease, 4 periods are distinguished: incubation, initial (pre-icteric), peak period (icteric) and convalescence.

Incubation period lasts 60-180 days, more often 2-4 months, in rare cases it is shortened to 30-45 days or extended to 225 days. The duration of the incubation period depends on the infecting dose and the age of the children. In case of massive infection (blood or plasma transfusions) incubation period is equal to 1.5-2 months, and with parenteral manipulations (subcutaneous and intramuscular injections) and especially with domestic infection, the incubation period is 4-6 months. In children of the first months of life, the incubation period is usually shorter (92.8 ± 1.6 days) than in older children age groups(117.8±2.6 days; p<0,05).

Clinical manifestations of the disease in this period are completely absent, but, as with hepatitis A, at the end of incubation, high activity of hepatocellular enzymes is constantly detected in the blood and markers of an active infection are detected: HBsAg, HBeAg, anti-HBc IgM.

Initial (pre-icteric) period. The disease often begins gradually (65%). An increase in body temperature is not always observed (40%) and usually not on the 1st day of illness. The patient experiences lethargy, weakness, increased fatigue, and decreased appetite. Often these symptoms are so mild that they are not noticed, and the disease begins with darkening of the urine and the appearance of discolored feces. In rare cases, the initial symptoms are pronounced: nausea, repeated vomiting, dizziness, drowsiness. Dyspeptic disorders often occur: loss of appetite up to anorexia, aversion to food, nausea, vomiting, flatulence, constipation, and less often diarrhea. Older children complain of dull pain in the abdomen. When examined during this period, general asthenia, anorexia, enlargement, hardening and tenderness of the liver, as well as darkening of urine and often discoloration of feces can be detected.

Muscular and joint pain, often found in adult patients, is very rare in children in the pre-icteric period.

Rarely in the pre-icteric period, skin rashes, flatulence, and stool disorders are observed.

Catarrhal phenomena are not at all characteristic of hepatitis B.

The most objective symptoms in the initial period are enlargement, hardening and tenderness of the liver.

Changes in peripheral blood in the initial period of hepatitis B are not typical. Only slight leukocytosis and a tendency to lymphocytosis can be noted; ESR is always within normal limits.

In all patients, already in the pre-icteric period, high activity of ALT, AST and other hepatocellular enzymes is detected in the blood serum; at the end of this period, the content of conjugated bilirubin in the blood increases, but the indicators of sediment samples, as a rule, do not change, and there is no dysproteinemia. HBsAg, HBeAg, and anti-HBc IgM circulate in the blood in high concentrations, and viral DNA is often detected.

The duration of the initial (pre-icteric) period can range from several hours to 2-3 weeks; on average 5 days.

Jaundice period (the height of the disease). 1-2 days before the onset of jaundice, all patients experience darkening of urine and most patients experience discoloration of stool. Unlike hepatitis A, hepatitis B, passing into the third, icteric period, in most cases is not accompanied by an improvement in general condition. On the contrary, in many children the symptoms of intoxication intensify.

Jaundice increases gradually, usually over 5-7 days, sometimes 2 weeks or longer. Yellowness can vary from faint canary or lemon yellow to greenish yellow or ocher yellow, saffron. The severity and shade of jaundice are associated with the severity of the disease and the development of cholestasis syndrome.

Having reached its peak severity, jaundice with hepatitis B usually stabilizes within 5-10 days, and only after that does it begin to decrease.

A rare symptom of hepatitis B in children is a skin rash. The rash is located symmetrically on the limbs, buttocks and torso, and is maculopapular, red, and up to 2 mm in diameter. When squeezed, the rash takes on an ocher color; after a few days, slight peeling appears in the center of the papules. These rashes should be interpreted as Gianotti-Crosti syndrome, described by Italian authors for hepatitis B.

In severe forms, at the height of the disease, manifestations of hemorrhagic syndrome may be observed: pinpoint or more significant hemorrhages in the skin.

In parallel with the increase in jaundice in hepatitis B, the liver enlarges, its edge thickens, and pain on palpation is noted.

An enlarged spleen is observed less frequently than an enlarged liver. The spleen is often enlarged in more severe cases and with a long course of the disease. Enlargement of the spleen is observed throughout the acute period with slow reverse dynamics. Often the spleen is palpated after the disappearance of other symptoms (with the exception of liver enlargement), which, as a rule, indicates a protracted or chronic course of the disease.

In the peripheral blood at the height of jaundice, the number of red blood cells tends to decrease. In severe forms, anemia develops. In rare cases, more severe changes in the bone marrow are possible, up to the development of panmyelophthisis.

During the icteric period, the number of leukocytes is normal or reduced. In the blood count, at the height of toxicosis, a tendency towards neutrophilia is revealed, and during the recovery period - towards lymphocytosis. ESR is usually within normal limits. Low ESR (1-2 mm/h) with severe intoxication in a patient with severe hepatitis B is an unfavorable sign.

Convalescent, recovery period. The total duration of the icteric period with hepatitis B ranges from 7-10 days to 1.5-2 months. With the disappearance of jaundice, children no longer complain, they are active, their appetite is restored, but in half of the patients hepatomegaly remains, and in 2/3 there is slight hyperfermentemia. Sometimes the thymol test is elevated and dysproteinemia, etc., are observed.

In the convalescent period, HBsAg and especially HBeAg are usually no longer detected in the blood serum, but anti-HBe, anti-HBc IgG and often anti-HBs are always detected.

Classification. Hepatitis B, like hepatitis A, is classified by type, severity and course.

The criteria for determining the type and distinguishing clinical forms are the same as for hepatitis A. However, along with mild, moderate and severe forms, a malignant form is also distinguished, which occurs almost exclusively in hepatitis B and hepatitis delta, and the course, in addition to acute and protracted, can be chronic.

Clinical and laboratory criteria for anicteric, erased, subclinical, as well as mild, moderate and severe forms of hepatitis B are not fundamentally different from those for hepatitis A.

Malignant form occurs almost exclusively in children 1 year of age.

Clinical manifestations of malignant forms depend on the prevalence of liver necrosis, the rate of their development, and the stage of the pathological process. There is an initial period of the disease or a period of precursors, a period of development of massive liver necrosis, which usually corresponds to a state of precoma and rapidly progressive decompensation of liver functions, clinically manifested by coma of I and II degrees.

The disease often begins acutely: body temperature rises to 38-39°C, lethargy, adynamia, and sometimes drowsiness appear, followed by attacks of anxiety or motor agitation. Dyspeptic disorders are expressed: nausea, regurgitation, vomiting (often repeated), sometimes diarrhea.

With the appearance of jaundice, the most constant symptoms are: psychomotor agitation, repeated vomiting with blood, tachycardia, rapid toxic breathing, bloating, severe hemorrhagic syndrome, increased body temperature and decreased diuresis. Vomiting "coffee grounds", sleep inversion, convulsive syndrome, hyperthermia, tachycardia, rapid toxic breathing, hepatic breath, liver shrinkage are observed only in malignant forms of the disease. Following these symptoms or simultaneously with them, a blackout occurs with the clinical symptoms of hepatic coma (see Fig. 75, 76 on the color plate).

Among the biochemical indicators, the most informative are the so-called bilirubin-protein dissociation (with a high content of bilirubin in the blood serum, the level of protein complexes decreases sharply) and bilirubin-enzyme dissociation (with a high content of bilirubin, there is a drop in the activity of hepatocellular enzymes, as well as a drop in the level of blood clotting factors ).

Flow. According to the classification, the course of hepatitis B can be acute, protracted and chronic.

An acute course is observed in 90% of children. The acute phase of the disease ends by the 25-30th day from the onset of the disease, and in 30% of children a complete recovery can already be stated. The rest have a slight enlargement of the liver (no more than 2 cm below the edge of the costal arch) in combination with hyperfermentemia, exceeding normal values ​​by no more than 2-4 times.

A protracted course is observed in approximately 10% of children. In these cases, hepatomegaly and hyperfermentemia persist for 4-6 months. Chronic course (chronic hepatitis B) as a result of manifest (icteric) forms does not occur in children. Chronic hepatitis almost always develops as a primary chronic process.

The most common outcome of acute manifest hepatitis B is recovery with complete restoration of liver function. As with hepatitis A, it is also possible to recover with an anatomical defect (liver fibrosis) or with the formation of various complications from the biliary tract and gastrointestinal tract. These outcomes of hepatitis B are almost no different from those of hepatitis A.

In practical work, in all cases of chronic hepatitis B, which appears to form as a result of an acute infection, it is necessary to exclude hepatitis A and hepatitis delta against the background of latent HBV infection.

Diagnostics. In hepatitis B, the supporting diagnostic signs include pronounced hepatolienal syndrome and gradually progressive jaundice. Only with hepatitis B is there an increase in jaundice of the skin and visible mucous membranes for 7 days or more. Following this, you can usually observe the so-called plateau of jaundice, when it remains intense for another 1-2 weeks. The size of the liver undergoes similar dynamics, and less commonly, the size of the spleen.

From epidemiological data, indications of previous operations, blood transfusions, injections and other manipulations associated with violation of the integrity of the skin or mucous membranes 3-6 months before the disease, as well as close contact with a patient with chronic hepatitis B or a virus carrier, are important.

Among biochemical tests, only low levels of the thymol test are typical for hepatitis B.

Specific laboratory research methods based on the determination of hepatitis B virus antigens (HBsAg, HBeAg) and antibodies to them (antiHBc, IgM and IgG, anti-HBe) in blood serum are of decisive importance in diagnosis.

Differential diagnosis. Acute hepatitis B must be differentiated primarily from other viral hepatitis: A, C, E, etc. The main differential diagnostic signs of these hepatitis are given in Table. 6.

Presented in table. 6 data should be considered indicative, since on their basis it is possible to carry out differential diagnosis only with group analysis, but a final etiological diagnosis is possible only by determining specific markers in the blood serum.

Objective difficulties may also arise in the differential diagnosis of hepatitis B with other diseases, the list of which is determined by the age of the children, the form, severity and phase of the pathological process.

Treatment. The general principles of treatment for patients with acute hepatitis B are the same as for hepatitis A. However, it must be taken into account that hepatitis B, unlike hepatitis A, often occurs in severe and malignant forms. In addition, the disease can result in the formation of chronic hepatitis and even cirrhosis, so specific recommendations for the treatment of patients with hepatitis B should be more detailed than for the treatment of patients with hepatitis A.

There is currently no fundamental objection to children with mild to moderate forms of hepatitis B being treated at home. The results of such treatment are no worse, and in some respects even better, than with hospital treatment.

Specific recommendations regarding physical activity, therapeutic nutrition and criteria for their expansion are in principle the same as for hepatitis A; one should only take into account that the terms of all restrictions for hepatitis B are usually somewhat extended in full accordance with the course of the disease.

In general, we can say that if the infection progresses smoothly, all restrictions on movement and nutrition should be lifted after 6 months from the onset of the disease, and sports can be allowed after 12 months.

Table 6. Differential diagnostic signs of viral hepatitis in children

Drug therapy is carried out according to the same principles as for hepatitis A. In addition to this basic therapy, for moderate and severe forms of hepatitis B, interferon can be used intramuscularly at a dose of 1 million units 1-2 times a day for 15 days. If necessary, treatment can be continued at 1 million units 2 times a week until recovery. The use of cycloferon is indicated both parenterally and in tablet form at a rate of 10-15 mg/kg body weight.

In severe forms of the disease, for the purpose of detoxification, hemodez, rheopolyglucin, 10% glucose solution up to 500-800 ml/day are administered intravenously, and corticosteroid hormones are prescribed at the rate of 2-3 mg/(kg. day) for prednisolone during the first 3- 4 days (until clinical improvement) followed by rapid dose reduction (course no more than 7-10 days). In children of the 1st year of life, moderate forms of the disease are also indications for prescribing corticosteroid hormones.

If a malignant form is suspected or there is a threat of its development, the following is prescribed:

Glucocorticosteroid hormones up to 10-15 mg/(kg day) for prednisolone intravenously in equal doses every 3-4 hours without an overnight break;

Plasma, albumin, hemodez, rheopolyglucin, 10% glucose solution at the rate of 100-200 ml/(kg day) depending on age and diuresis;

Proteolysis inhibitors: trasylol, gordox, contrical in an age-related dose;

Lasix 2-3 mg/kg and mannitol 0.5-1 g/kg intravenously in a slow stream to enhance diuresis;

According to indications (disseminated intravascular coagulation syndrome), heparin 100-300 units/kg intravenously.

To prevent the absorption of endotoxin from gram-negative bacteria and toxic metabolites from the intestine resulting from the vital activity of microbial flora, enterosorption therapy (enterosgel, enterodesis, etc.) is prescribed. Enterosorption prevents the reabsorption of toxic substances in the lumen and interrupts their circulation in the body. It should be taken into account that the level of toxic substances passing through the intestinal barrier depends on the condition of the mucous membrane, therefore, the result of enterosorption also depends on the effect of the enterosorbent on the mucous membrane, therefore it is preferable to use enterosorbent Enterosgel, which has exceptional hydrophobic and selective properties and clearly promotes the regeneration of the mucosa intestinal lining. Gastric lavage, high cleansing enemas, and broad-spectrum antibiotics (gentamicin, polymyxin, ceporin) are also prescribed.

If the complex of therapeutic measures is ineffective, repeated sessions of plasmapheresis should be performed. Repeated hemosorption sessions and replacement blood transfusions are less effective.

It is advisable to include hyperbaric oxygenation in the complex of pathogenetic agents (1-2 sessions per day: compression 1.6-1.8 atm, exposure 30-45 minutes).

The success of treatment of malignant forms mainly depends on the timeliness of the above therapy. If deep hepatic coma develops, therapy is ineffective.

Just as with hepatitis A, with cholestatic forms of hepatitis B and in the period of convalescence with a prolonged course and pronounced residual effects, ursodeoxycholic acid (ursosan) is indicated. The drug is prescribed in usual doses (10-15 mg/kg/day). The duration of treatment is determined in accordance with the clinical and laboratory manifestations of the disease.

Discharge from hospital and follow-up. Typically, children are discharged on the 30-40th day from the onset of the disease, and moderate hepatomegaly and hyperfermentemia are allowed. Upon discharge from the hospital, the patient is given a leaflet outlining the recommended regimen and diet. If the child continues to have HBsAg at the time of discharge, information about this is entered into the outpatient observation card and reported to the SES at the place of residence.

Subsequent monitoring of convalescence is best carried out in a consultation and dispensary office, organized at an infectious diseases hospital. If it is impossible to organize such an office, dispensary observation of survivors of hepatitis B should be carried out by the attending physician. The first clinical examination is carried out no later than a month after discharge from the hospital, subsequent ones - after 3; 4; 6 months In the absence of subjective complaints and objective deviations from the norm, convalescents are removed from the dispensary register, otherwise they continue to be examined once a month until complete recovery.

Children with significant or increasing clinical and laboratory changes, as well as with exacerbation of the disease or suspected development of chronic hepatitis, are readmitted to the hospital to clarify the diagnosis and continue treatment. Children without signs of chronic hepatitis, but with persistent HBs antigenemia, are also subject to repeated hospitalization. Subsequently, such children undergo clinical and laboratory examination as indicated.

Patients are removed from the dispensary register when, during 2 regular examinations, normalization of clinical and biochemical data is established, and HBsAg is not detected in the blood.

Clinical observation is indicated for children who have received transfusions of blood products (plasma, fibrinogen, leukocyte mass, red blood cell mass, etc.). This is especially true for children 1 year of age. The follow-up period is 6 months after the last blood transfusion. During this period, the child is examined monthly and, if hepatitis is suspected, is hospitalized in an infectious diseases hospital. In doubtful cases, blood serum is examined for the activity of hepatocellular enzymes and HBsAg.

Prevention consists primarily of a thorough examination of all categories of donors with a mandatory blood test for HBsAg at each blood donation using highly sensitive methods for its identification (ELISA, radioimmunoassay - RIA), as well as determination of ALT activity.

Persons who have had viral hepatitis in the past, patients with chronic liver diseases, as well as persons who have received transfusions of blood and its components within the last 6 months are not allowed to donate. It is prohibited to use blood and its components from donors who have not been tested for HBsAg for transfusion.

To improve the safety of blood products, it is recommended that donors be tested not only for HBsAg, but also for anti-HBc. Removal from donation of persons with anti-HBc, considered as hidden carriers of HBsAg, practically eliminates the possibility of post-transfusion hepatitis B.

To prevent infection of newborns, all pregnant women are tested twice for HBsAg using highly sensitive methods: when registering a pregnant woman (8 weeks of pregnancy) and when registering for maternity leave (32 weeks). If HBsAg is detected, the question of pregnancy should be decided strictly individually. It is important to consider that the risk of intrauterine infection of the fetus is especially high if a woman has HBeAg and is negligible if it is absent, even if HBsAg is detected in high concentrations. The risk of infection of the child during delivery by cesarean section is also significantly reduced.

Interruption of infection transmission routes is achieved by the use of disposable syringes, needles, scarifiers, probes, catheters, blood transfusion systems, other medical instruments and equipment used during manipulations associated with violation of the integrity of the skin and mucous membranes.

All medical instruments and reusable equipment must undergo thorough pre-sterilization cleaning and sterilization after each use.

For the prevention of post-transfusion hepatitis, strict adherence to the indications for hemotherapy is of great importance. Transfusion of canned blood and its components (erythrocyte mass, plasma, antithrombin, etc.) is done only for health reasons and noted in the medical history. It is necessary to switch, if possible, to transfusion of blood substitutes or, as a last resort, transfusion of its components (albumin, specially washed red blood cells, protein, plasma). This is due to the fact that pasteurization of plasma (60°C, 10 hours), although it does not guarantee complete inactivation of HBV, still reduces the risk of infection; The risk of infection during transfusion of albumin and protein is even lower, and the risk of infection during transfusion of immunoglobulins is negligible.

In departments at high risk of hepatitis B infection (hemodialysis centers, resuscitation units, intensive care wards, burn centers, oncology hospitals, hematology departments, etc.), hepatitis B prevention is ensured through strict adherence to anti-epidemic measures (use of one disposable instrumentation, assignment of each device to a fixed group of patients, thorough cleaning of blood from complex medical devices, maximum separation of patients, limitation of parenteral interventions, etc.). In all these cases, HBsAg identification is carried out using highly sensitive methods and at least once a month.

To prevent occupational infections, all employees must work with blood wearing rubber gloves and strictly observe personal hygiene rules.

To prevent the spread of infection in families of patients with hepatitis and HBV carriers, routine disinfection is carried out, personal hygiene items (toothbrushes, towels, bed linen, washcloths, combs, shaving accessories, etc.) are strictly individualized. All family members are explained under what conditions infection can occur. Family members of patients with chronic hepatitis B and carriers of HBsAg are subject to medical supervision.

Specific prevention of hepatitis B is achieved through passive and active immunization of children at high risk of infection.

For passive immunization, immunoglobulin with a high content of antibodies to HBsAg is used (titer in the passive hemagglutination reaction is 1:100,000 - 1:200,000). This immunoglobulin is obtained from the plasma of donors in whose blood anti-HBs is detected in high titer.

Born from mothers who are carriers of HBsAg or who have developed acute hepatitis B in the last months of pregnancy (immunoglobulin is administered immediately after birth, and then again after 1, 3 and 6 months);

After virus-containing material enters the body (blood or its components are transfused from a patient or a carrier of HBV, accidental cuts, injections with suspected contamination with virus-containing material); in these cases, immunoglobulin is administered in the first hours after the suspected infection and after 1 month;

If there is a long-term threat of infection - for children admitted to hemodialysis centers, patients with hemoblastosis, etc. (re-administered at various intervals - after 1-3 months or every 4-6 months); the effectiveness of passive immunization depends primarily on the timing of immunoglobulin administration; when administered immediately after infection, the preventive effect reaches 90%, within up to 2 days - 50-70%, and when administered after 5 days, immunoglobulin prophylaxis is practically ineffective.

With intramuscular injection of immunoglobulin, the peak concentration of anti-HBs in the blood is reached after 2-5 days. To obtain a faster protective effect, immunoglobulin can be administered intravenously.

The elimination period of immunoglobulin ranges from 2 to 6 months, but a reliable protective effect is ensured only in the 1st month after administration, therefore, to obtain a prolonged effect, repeated administration of immunoglobulin is necessary. In addition, the use of immunoglobulin is effective only at a low infectious dose of HBV. In case of massive infection (blood transfusion, plasma, etc.), immunoglobulin prophylaxis is ineffective.

Despite the shortcomings, the introduction of specific immunoglobulin should take its rightful place in the prevention of hepatitis B. According to the literature, timely specific immunoglobulin prophylaxis can prevent hepatitis B infection in 70-90% of vaccinated people.

For active prevention of hepatitis B, genetically engineered vaccines are used.

Several recombinant vaccines against hepatitis B have been created in our country (JSC NPK Combiotech Regevak B and other vaccines). In addition, several foreign drugs have been registered and approved for use (Engerix B; NV-VAX II, Euvax; Shanvak-B; Eberbiovak).

The following are subject to active immunization against hepatitis B:

Newborns from mothers with hepatitis or carriers of HBsAg, especially if they have HBeAg;

Newborns in areas where hepatitis B is endemic with HBsAg carriage rates greater than 5%;

Patients who often undergo various parenteral procedures (chronic renal failure, diabetes mellitus, blood diseases, proposed surgery using a heart-lung machine, etc.);

Persons in close contact with HBsAg carriers (in families, closed children's groups);

Medical personnel of hepatitis departments, hemodialysis centers, blood service departments, surgeons, dentists, pathologists;

Persons who have been accidentally injured by instruments contaminated with the blood of patients with hepatitis B or carriers of HBsAg.

Vaccination is carried out three times according to scheme 0; 1; 6 months Other schemes are also allowed: 0; 1; 3 months or 0; 1; 2; 12 months Revaccination is carried out every 5 years.

Only persons who do not have HBV markers detected in their blood (HBsAg, anti-HBc, anti-HBs) are subject to active immunization. If one of the markers of hepatitis B is present, vaccination is not carried out.

The effectiveness of vaccination is very high. Numerous studies show that when the vaccine is administered according to scheme 0; 1; After 6 months, 95% of individuals develop protective immunity, which provides reliable protection against HBV infection for 5 years or more.

There are no contraindications to vaccination against hepatitis B. The vaccine is safe and areactogenic.

Vaccination can reduce the incidence of hepatitis B by 10-30 times.

To prevent vertical transmission of HBV, the first phase of vaccines is administered immediately after birth (no later than 24 hours), then vaccinated after 1; 2 and 12 months For this purpose, combined passive-active immunization of newborns from mothers with hepatitis B or virus carriers can be used. Specific immunoglobulin is administered immediately after birth, and vaccination is carried out in the first 2 days, then at age 0; 1; 2 months with revaccination at 12 months. This passive-active immunization reduces the risk of infection of children from mothers with HBeAg from 90 to 5%.

Widespread implementation of vaccination against hepatitis B will reduce the incidence of not only acute but also chronic hepatitis B, as well as cirrhosis and primary liver cancer.

HEPATITIS DELTA

B16.0 - acute hepatitis B with delta agents (co-infection) and hepatic coma;

B16.1 - acute hepatitis B with delta agents (co-infection) without hepatic coma;

B17.0 - acute delta (super) - infection of the hepatitis B virus carrier.

Etiology. Hepatitis delta virus (HDV) is a spherical particle with a diameter of 35-37 nm, the outer shell of which is the HBV surface antigen (HBsAg). At the center of the particle is a specific antigen (AgD) containing small RNA (genome). For replication and expression, HDV requires the obligate HBV helper function, as a result of which it is one of the defective viruses with an incomplete genome. It has been established that the delta antigen is located mainly in the nuclei of hepatocytes in the form of aggregates of individual particles 20-30 nm in size, localized in the chromatin zone and occasionally in the cytoplasm in association with ribosomes or in the hyaloplasm. The delta antigen is resistant to heat and acids, but is inactivated by alkalis and proteases. The experimental infection can be reproduced on chimpanzees.

Epidemiology. The source of the disease are patients with acute and especially chronic hepatitis delta, as well as healthy carriers IOP and even carriers of antibodies to IOP.

IOP is transmitted exclusively by the parenteral route - through transfusion of virus-containing blood and its preparations, as well as through the use of needles, catheters, probes and other medical instruments contaminated with virus-containing blood. The risk of infection with IOP is especially high among regular recipients of donor blood or blood products (patients with hemophilia, hematological malignancies, and other chronic diseases), as well as among people serving hemodialysis centers, surgeons, and drug addicts.

Infection occurs through HBsAg-positive blood or its preparations containing antibodies to IOP. A donor of such blood usually has chronic hepatitis and delta antigen can always be detected in liver cells.

Transplacental transmission of IOP from mother to fetus is possible. However, more often newborns become infected during childbirth or immediately after birth as a result of contamination with maternal blood containing IOP through damaged skin and mucous membranes.

Persons who have not had hepatitis B, as well as carriers of HBV, are susceptible to IOP. The greatest susceptibility is observed in young children and in persons with chronic hepatitis B.

Pathogenesis. When infected with IOP, coinfection and superinfection can develop. Coinfection occurs in individuals who have not had viral hepatitis B and are not immune to HBV. Superinfection is possible when patients with chronic hepatitis B or carriers of HBV become infected. When coinfected, hepatitis B and hepatitis delta occur with corresponding serological responses to HBV and HDV. With superinfection, a clinical picture of acute hepatitis develops, accompanied by the appearance of antibodies to IOP with a simultaneous drop in the level of HBV markers in the blood and liver, which is explained by the influence of reproducing IOP on HBV. HDV superinfection usually manifests itself within a period of 3 weeks to 3 months after infection and, as a rule, ends in the formation of a joint chronic infection of HBV and HDV or the occurrence of chronic hepatitis delta against the background of ongoing carriage of HBV.

Pathomorphology. It is not possible to identify any specific morphological signs unique to delta hepatitis. Signs of a severe inflammatory process predominate.

Clinical manifestations. Depending on the mechanism of development, 4 forms of the disease are distinguished: mixed acute infection of HBV and HDV (co-infection); delta HDV superinfection; chronic concurrent hepatitis B and hepatitis delta; chronic hepatitis delta due to HBV carriage.

Coinfection. The incubation period ranges from 8 to 10 weeks. The disease manifests itself with the same clinical symptoms as acute hepatitis B, the initial period of the disease is often more defined: increased body temperature to 38-39 ° C, adynamia, decreased appetite, nausea, vomiting, abdominal pain, enlarged liver and spleen. In the blood serum, the content of total bilirubin is increased due to the direct fraction, the activity of hepatocellular enzymes is high, and dysproteinemia is noted.

With a favorable course, the duration of the disease is 1.5-3 months. Some children may develop protracted forms with clinically significant exacerbations, repeated increases in bilirubin levels and the activity of hepatocellular enzymes in the blood serum.

The formation of chronic hepatitis in the outcome of manifest clinical forms is not observed. In children in the first months of life, malignant hepatitis often occurs with a fatal outcome. The absence of chronicity of acute manifest forms of coinfection does not exclude the possibility of the formation of primary chronic hepatitis B and hepatitis delta, which occur latently, without an acute manifest phase.

IOP superinfection. When HDV infection is superimposed on chronic HBV infection, such as chronic hepatitis or as a healthy carrier, the incubation period is 3-4 weeks. In these cases, IOP infection is usually manifested by a clinical picture of acute hepatitis: increased body temperature to 38-39°C, malaise, general weakness, nausea, vomiting, abdominal pain. After 2-3 days, dark urine, discolored feces, icteric staining of the sclera and skin appear, and the liver and spleen become enlarged. At the same time, the content of total bilirubin in the blood serum increases 3-5 times, mainly due to the conjugated fraction, the activity of hepatic cellular enzymes increases 4-10 times, the thymol test indicators increase, the sublimate test and prothrombin index significantly decrease. The course of the disease is often severe, up to the occurrence of a malignant form with a fatal outcome in some patients. In other cases, chronic hepatitis delta is formed with high activity of the process.

Chronic active hepatitis B and hepatitis delta should be considered as a mixed chronic infection, since the pathological process is caused by actively occurring hepatitis B and hepatitis delta. In children, the disease manifests itself as severe symptoms of intoxication in the form of increased fatigue, emotional instability, decreased appetite, signs of dysfunction of the gastrointestinal tract (nausea, feeling of heaviness in the epigastric region, right hypochondrium, flatulence). Some patients have mild icterus of the skin, and all have enlarged liver and spleen. Multiple bruises on the extremities are constantly detected, nosebleeds are sometimes noted, telangiectasia, palmar erythema and other extrahepatic signs are common. In the blood serum of all patients, high activity of hepatocellular enzymes, a decrease in prothrombin, dysproteinemia, as well as HBsAg, HBeAg and markers of current hepatitis delta (HDV RNA and anti-HDV IgM) are detected. The course of the disease can be severe, with alternating short remissions and long-term exacerbations. After 5-6 years, the disease can already be interpreted as chronic active hepatitis delta with the formation of liver cirrhosis (see Fig. 77, 78, 79 on the color insert). These children have a pronounced hepatolienal syndrome with a sharp thickening of the liver, hemorrhagic manifestations, extrahepatic signs, high activity of hepatocellular enzymes, low levels of sublimate test, prothrombin index and the phenomenon of progressive dysproteinemia. Changes in the marker spectrum indicate continued HDV activity (anti-HDV IgM is detected) in the absence of HBV replicative activity (HBsAg and anti-HBe are detected).

Diagnosis hepatitis delta is established based on the detection of HDV RNA, HBV DNA, IgM and IgG antibodies in the blood by PCR method to HDV and HBV.

Based only on clinical data, HDV infection can be assumed if a patient with chronic hepatitis B or a so-called healthy carrier of HBsAg experiences a clinically significant exacerbation with symptoms of intoxication, jaundice, a sharp enlargement of the liver and an increase in the activity of hepatocellular enzymes.

Treatment for hepatitis, the delta is the same as for hepatitis B, and is built taking into account the severity of clinical manifestations and the course of the disease. Since the course of hepatitis delta is often unpredictable, all patients are subject to mandatory hospitalization in the hepatitis department of an infectious diseases hospital.

Prevention. In the prevention of hepatitis delta, the leading role is played by the prevention of hepatitis B. It is necessary to carefully protect HBV carriers and patients with chronic hepatitis B from superinfection with HDV. Such superinfection can occur not only during the transfusion of infected blood products or during parenteral manipulations, but also during close household contact through microtrauma of the skin and mucous membranes.

HEPATITIS C

Etiology. Hepatitis C virus (HCV) belongs to the flavivirus family. It has a diameter of 22 to 60 nm and is found both in blood and in liver extracts from humans or experimentally infected chimpanzees. Unlike other hepatitis viruses, it is found in the blood serum of patients in extremely low concentrations, and the immune response in the form of specific antibodies is very weak and late. The virus is sensitive to chloroform and formalin; when heated to 60°C it is inactivated within 10 hours, and when boiled - within 2 minutes. Sterilization of blood products using ultraviolet rays is effective.

Epidemiology. In Western Europe and the USA, up to 95% of all cases of post-transfusion and parenteral hepatitis are caused by HCV. The disease occurs after transfusion of virus-containing blood, plasma, fibrinogen, antihemophilic factor and other blood products. Outbreaks of hepatitis C have been noted among patients with immunodeficiencies after intravenous infusions of immunoglobulin drugs. Hepatitis C is the leading acute hepatitis in hemodialysis centers, among patients in organ transplant departments, in oncology hospitals, plasmapheresis centers, etc.

HCV is transmitted exclusively by the parenteral route, mainly with blood products and during various invasive interventions, including through microtrauma during household contact. The possibility of perinatal transmission of infection from mother to fetus transplacentally, as well as during childbirth and immediately after birth when the child is contaminated with mother’s blood through damaged skin has been shown. Sexual transmission of HCV is quite likely.

Pathogenesis. In the mechanism of damage to liver cells in hepatitis C, the leading role is played by immune cytolysis, realized by T-cell cytotoxicity directed against infected hepatocytes. The possibility of direct cytopathic effects of the virus on liver cells is possible. In the pathogenesis of the formation of chronic forms of the disease, the weakened ability of blood mononuclear cells to produce γ-interferon, as well as a change in the ratio of immunoregulatory subpopulations of T-helpers and T-suppressors with a predominance of the latter and the associated insufficiently effective T-cell and humoral immune response to the action, are of decisive importance pathogen and infected hepatocytes. The increased ability of the HCV antigen to masquerade into immune complexes is also of certain importance, which brings this disease closer to the immune complex.

Pathomorphology. Morphological changes in the liver with hepatitis C do not have strict specificity. However, in acute hepatitis C, portal inflammation is less pronounced, focal necrosis is less common, and steatosis is significantly more noticeable compared to that in hepatitis A and hepatitis B.

With the formation of chronic hepatitis, there is a significant increase in the portal and periportal inflammatory reaction with the accumulation of mononuclear elements, and mild fibrosis with a tendency to septal proliferation is detected. Diffuse dystrophic changes ranging from mild to severe, including balloon degeneration and necrosis, are observed in hepatocytes.

A chronic process in the liver may fit into the morphological picture of persistent hepatitis, but in most cases it is active hepatitis with relatively rare bridging necrosis and moderate lymphoid infiltration.

Clinical manifestations. The incubation period averages 7-8 weeks, with fluctuations from several days (with massive infection) to 26 weeks. The disease begins gradually with asthenovegetative and dyspeptic manifestations: lethargy, malaise, nausea, and sometimes low-grade body temperature. Abdominal pain and sometimes vomiting are possible. After a few days, dark urine and discolored feces appear. In all patients, the liver is enlarged, and sometimes the spleen is enlarged. Jaundice appears rarely, only in 15-40% of patients. In the absence of jaundice, the leading symptoms are malaise, asthenia and enlarged liver. In the blood serum of all patients, the activity of ALT and AST is increased, in some cases the content of total bilirubin is increased due to the direct fraction, a decrease in prothrombin, dysproteinemia, etc. are possible. The indicators of functional liver tests fully correspond to the severity of liver damage and the stage of the pathological process.

Viral hepatitis C is classified in the same way as other viral hepatitis. There are typical and atypical variants of the disease.

Based on severity, they are divided into mild, moderate, severe and malignant, and according to their course - acute, protracted and chronic forms.

The characteristics of clinical forms and the criteria for their diagnosis are the same as for other hepatitis.

Flow. The acute course of hepatitis C occurs in 10-20% of cases, in other children the disease takes a chronic course. The transition to the chronic stage is manifested by persistent hyperfermentemia with a relatively satisfactory general condition, complete absence of complaints, slight enlargement and hardening of the liver. In the stage of established chronic hepatitis, patients may complain of increased fatigue, weakness, and dyspeptic symptoms. Upon examination, vascular changes can be detected (telangiectasia, palmar erythema), the liver is always enlarged, and often the spleen is enlarged. Despite the low severity of clinical symptoms, the pathological process in the liver morphologically in most cases corresponds to chronic active hepatitis, often with signs of developing cirrhosis.

Diagnostics. The diagnosis of hepatitis C is established when specific antibodies to the structural and non-structural proteins of the virus are detected in the blood serum by ELISA, as well as viral RNA by PCR.

Treatment. The general principles of treatment for patients with acute and chronic hepatitis C are the same as for other viral hepatitis. Prescribe bed rest, diet, and symptomatic medications. For malignant forms, corticosteroid hormones are used, and in patients with chronic hepatitis, recombinant interferon preparations (viferon, intron A, roferon A, etc.) are successfully used.

To relieve the toxic load on the liver, it is necessary to carry out enterosorption therapy (enterosgel, enterodesis). For long-term enterosorption, a selective enterosorbent with pronounced hydrophobic properties is recommended. In children with chronic viral liver damage (HBV and HCV), combination therapy using drugs with antiviral activity with a different mechanism of action is indicated: for chronic viral hepatitis B - lamivudine and cycloferon or viferon and cycloferon.

As a means of pathogenetic therapy for chronic hepatitis C, ursodeoxycholic acid (ursosan) is prescribed, which has a corrective effect on the main links of pathogenesis that predetermine the chronic course of the infection (anticholestatic, immunomodulatory, antifibrotic, antioxidant, antiapoptotic). The drug Ursosan is prescribed at a dose of 10-15 mg/kg. days both during treatment with interferons and as monotherapy with a course duration of 3-6 months to one year.

Prevention. The principles of preventing hepatitis C are the same as for hepatitis B. The use of disposable syringes, infusion systems, catheters, as well as compliance with the rules of sterilization of surgical, dental and other instruments lead to a significant reduction in the incidence of not only hepatitis B, but also hepatitis C.

Testing blood products for anti-HCV and transaminase activity and then excluding positive samples leads to a significant reduction in the incidence of hepatitis C among blood product recipients.

HEPATITIS G

Based on the composition of nucleotide and amino acid sequences, the G virus, together with HCV, forms a group of hepatitis-associated viruses within the flavivirus family (Flaviviridae). In this case, the HCV RNA is constructed according to a scheme characteristic of the entire flavivirus family: at the 5th end there is a zone encoding structural proteins, at the 3rd end there is a zone encoding non-structural proteins.

The RNA molecule contains one open reading frame; encodes the synthesis of a precursor polyprotein consisting of approximately 2900 amino acids. The virus has constant regions of the genome (used to create primers used in PCR), but is also characterized by significant variability, which is explained by the low reliability of the reading function of the viral RNA polymerase. The virus is believed to contain a core protein (nucleocapsid protein) and surface proteins (supercapsid proteins). Various variants of HCV nucleotide sequences in different isolates are regarded as different subtypes within a single genotype or as intermediate between genotypes and subtypes. There are several genotypes of GBV (GBV-C and GBV-prototype, etc.).

Epidemiology. CHG is found everywhere. The frequency of HCV RNA detection clearly correlates with blood transfusions and multiple parenteral interventions. HCV is very common among drug addicts who inject drugs intravenously, people receiving hemodialysis, blood donors, and also among patients with chronic hepatitis C.

Sexual and vertical transmission of infection cannot be excluded.

Pathogenesis. HCV RNA begins to be detected in blood serum 1 week after transfusion of infected blood components. More than 9 years of observation of individuals with persistent HCV infection showed both high (up to 10 7 /ml) and low (up to 10 2 /ml) RNA titers; titers may remain constant during the observation period or they fluctuate widely (up to 6 orders of magnitude), as well as periodic disappearance of HCV RNA in serum samples. HCV RNA is also found in liver tissue. During experimental infection (chimpanzees), liver damage, intralobular necrotic-inflammatory changes and inflammatory infiltration along the portal tracts are found, similar to those with hepatitis C.

Pathomorphology. Pathological changes in liver tissue with hepatitis G correspond to those with hepatitis C.

Clinical manifestations. The disease manifests itself in a wide range of liver lesions - from acute cyclic hepatitis and chronic forms to asymptomatic carriage.

In acute monoinfection, a slight increase in body temperature, asthenodyspeptic symptoms in the form of lethargy, nausea, abdominal pain, and vomiting may be observed. At the height of the disease, the liver enlarges, and less often, the spleen. In the blood serum, the activity of ALT and AST is always increased, and the level of bilirubin, as a rule, is within normal limits, HGG RNA is detected. The course of the disease can be acute, protracted and chronic. The clinical manifestations of these forms are practically indistinguishable from those of viral hepatitis C.

Diagnostics. Specific diagnosis of hepatitis G is based on detection of HCV RNA in blood serum using PCR. The primers used for PCR are specific to the 5NCR, NS3 and NS5a regions of the viral genome as the most conserved ones.

Another way to diagnose HCV infection is to test for the detection of antibodies to the surface protein E2 of HGV using ELISA.

Treatment. The principles of therapy for hepatitis G are the same as for hepatitis C.

Prevention. A set of the same measures is being carried out as to prevent other viral hepatitis with pyrexial infection.

Viral hepatitis A (or Botkin's disease)– a special type of viral hepatitis; it does not have chronic forms and has a fecal-oral transmission mechanism. A less common type of viral hepatitis has the same properties - hepatitis E.

Hepatitis viruses A and E do not have a direct damaging effect on the liver. Hepatitis - inflammation of the liver - occurs when viruses penetrate liver cells, thereby causing a reaction of protective blood cells against the altered liver tissue.

Hepatitis A is one of the most common infections in the world. Many people get this disease in childhood, which is associated with the greater prevalence of hepatitis A in children's institutions, in closed groups. Children tolerate the infection much more easily than adults; many suffer an asymptomatic form of hepatitis A and acquire lifelong immunity. In adults, severe forms of hepatitis requiring hospitalization are more common, most likely due to various concomitant diseases.

Viral hepatitis A is most widespread in countries with warm climates and poor sanitary conditions. Therefore, the likelihood of catching hepatitis A increases when traveling to hot countries: Egypt, Tunisia, Turkey, Central Asia, India, etc.

Hepatitis E distributed in the countries of Southeast Asia, Africa, and Central America. In our latitudes, hepatitis E is much less common.

Hepatitis A virus

The hepatitis A virus is extremely resistant to external influences and can persist in the environment for a long time.

• Withstands boiling for 5 minutes.
• Chlorination - 30 minutes.
• Formaldehyde treatment - 3 hours.
• Withstands treatment with 20% ethyl alcohol.
• Withstands acidic environments (pH 3.0).
• It lives in water at a temperature of 20ºC for 3 days.
• In meat and shellfish dishes at a temperature of 80 ºС it is active for 20 minutes.

How can you become infected with hepatitis A?

The source of infection is a sick person who releases viruses into the environment with feces. Viruses entering water and food penetrate the body of a healthy person and can cause disease. Especially dangerous are dishes prepared from insufficiently heat-treated seafood. In addition, infection often occurs by eating vegetables and fruits, which may themselves contain hepatitis A viruses or may be washed with contaminated water.

A less common mechanism of transmission is through contaminated blood. This occurs during blood transfusions, drug addicts using shared syringes, and also during homosexual contacts.

Development of hepatitis A and E virus

Hepatitis viruses penetrate the intestines through the mouth, from there, being absorbed into the blood, they penetrate the liver cells, causing their inflammation through an attack by the body's own immune cells. The viruses then enter the bile ducts, and from there into the intestines and the environment.

A sick person is dangerous to others in the last week of the incubation period and in the first week of the disease. The incubation period is the period from infection to the first manifestations of the disease. In the case of hepatitis A, it is 14-28 days. And in case hepatitis E can reach 60 days (average 40 days).

While the virus is in the blood, there is no jaundice, there are general signs of intoxication, and the infection occurs under the guise of an acute respiratory viral infection.

The appearance of jaundice means that there are no more viruses in the blood and the immune response is fully formed. However viral hepatitis A often occurs without jaundice.

The appearance of jaundice indicates damage to 70% of the liver, so all patients with jaundice are recommended to be treated in a hospital setting. However, in most cases, with adherence to the regimen and adequate treatment, the structure and function of the liver is completely restored.

Symptoms of hepatitis A and E

Anicteric period with hepatitis A and E virus

The anicteric period can last for 1-2 weeks. In this case, general symptoms are observed that are very similar to the symptoms of flu and colds.

• Decreased appetite.
• Fatigue.
• Malaise.
• Fever (usually 38-39ºС, rarely the temperature rises to 40 ºС).
• Pain in muscles and joints.
• Headache.
• Cough.
• Runny nose.
• Sore throat.
• Nausea and vomiting.
• Abdominal pain.

Jaundice period with hepatitis A and E virus

The first symptom that makes you wary is darkening of urine. The urine turns dark brown, “the color of dark beer.” Then the eye sclera and mucous membranes of the eyes and mouth turn yellow, which can be determined by raising the tongue to the upper palate; The yellowing is also more noticeable on the palms. Later the skin turns yellow.

With the onset of the icteric period, general symptoms decrease and the patient usually feels better. However, in addition to yellowing of the skin and mucous membranes, heaviness and pain appear in the right hypochondrium. Sometimes there is discoloration of stool, which is associated with blockage of the bile ducts.

Full recovery occurs in 1-2 months.

Severe forms of hepatitis A and E virus

Severe forms of the disease include the so-called cholestatic forms when bile stagnation occurs, which is caused by inflammation of the walls of the bile ducts. In this case, the stool becomes lighter and skin itching occurs, which is caused by irritation of the skin by bile components.

Fulminant hepatitis is especially dangerous, in which massive liver necrosis develops, acute liver failure and often the death of the patient. At hepatitis A the fulminant form occurs extremely rarely, and when hepatitis E– its frequency is 1-2%. However, there is a particular danger hepatitis E represents for pregnant women - the frequency of the fulminant form is 25%

Mortality at hepatitis A ranges from 1 to 30%. Mortality increases with age, as well as in chronic carriers of other viral hepatitis.

Who is more likely to get hepatitis A and E virus?

• People traveling to countries where the incidence is higher (endemic regions)
• Children attending preschool institutions
• Workers of preschool institutions
• Food service workers
• Sewage and water workers
• People whose family members have hepatitis A
• Homosexuals
• Drug addicts

It should be noted that in countries with a high prevalence hepatitis A, as well as in rural areas, many people contract hepatitis A in childhood, often in mild or asymptomatic forms, thereby acquiring lifelong immunity. Whereas people living in cities suffer from hepatitis A much less frequently, and therefore have a greater risk of becoming infected through contact with a sick person, as well as when traveling to endemic areas.

Prevention of hepatitis A and E virus

General preventive measures come down to the basic principles of general hygiene. It is necessary to wash your hands before eating, wash fruits and vegetables with water, the purity of which is beyond doubt. Do not eat under-processed meat, fish, especially seafood.

Immunoglobulin

With the help of normal human immunoglobolin, so-called passive immunization is achieved, i.e. a person is injected with ready-made antibodies (protective proteins) against hepatitis A viruses. The duration of action of these antibodies is 2 months. When the drug is administered at the beginning of the incubation period, it prevents the development of the disease.

Immunoglobulin can be used in people who have been in close contact with the sick person no later than 2 weeks after the suspected infection; as well as in people located in an endemic region.

Immunoglobulin is safe and well tolerated; HIV infection cannot be transmitted through it, since the virus is inactivated during the manufacture of the drug.

Vaccination

Vaccines are available in Russia, which are viruses grown in cell culture and inactivated by formaldehyde. There are several vaccines of this type: Hep-A-in-vac (Russia), Avaxim (France), Havrix (Belgium), Vakta (USA).

Vaccination can be given to children starting from 2 years of age. After a single vaccination, immunity is formed in 1-4 weeks (depending on the type of vaccine), so it can be used 1-4 weeks or more before traveling to countries with a high prevalence of hepatitis A. After a single immunization, immunity is formed for 2 years; after two times – for more than 20 years.

For adults, the vaccine is administered intramuscularly - 2 doses with an interval of 6-12 months. Children aged 2-18 years are administered intramuscularly with 2 half doses at monthly intervals and a third dose after 6-12 months.

Complications of hepatitis A and E

Hepatitis A, which arises against the background of complete health, almost always ends in recovery. In elderly patients with concomitant diseases, especially with chronic carriage of other viral hepatitis, the prognosis worsens, and a protracted course of the disease is more often observed.

In a small number of patients, weeks and months after the illness, a relapse may occur, i.e. return of all symptoms of the disease: intoxication, jaundice. But even in these cases, hepatitis does not become chronic.

Besides, viral hepatitis E can cause hemolysis - destruction of blood cells - red blood cells, which can lead to kidney damage and acute renal failure.

Liver dysfunction after surgery hepatitis A are extremely rare, mainly in older patients. However, there are cases when hepatitis A occurs in an anicteric form, under the guise of ARVI, when the patient does not comply with bed rest; this can lead to the formation of scar tissue in the liver - hepatic fibrosis, which is dangerous due to the development of bile duct dyskinesia - disruption of the normal passage of bile.

With hepatitis E, liver cirrhosis occurs in 5% of cases.

Diagnosis of hepatitis A

Diagnosis is primarily based on clinical data - i.e. manifestations of the disease.

To confirm the diagnosis of viral hepatitis, a number of laboratory tests are performed. Biochemical blood tests may reveal significant increases in bilirubin and liver enzymes, confirming liver damage.

Then a differential diagnosis of viral hepatitis is carried out. Specific diagnosis of hepatitis A is based on the determination of antibodies in the virus in the blood, and specific antibodies characteristic of acute hepatitis are determined.

Regimen and diet for acute hepatitis

During acute hepatitis, it is better to stay in bed. Lying down improves blood supply to internal organs, including the liver, which helps normal restoration of liver cells.

For acute hepatitis, a special type of diet is indicated - diet No. 5.

Food should be consumed 5-6 times a day, warm.

Allowed:

• Dried bread or day-old bread.
• Soups made from vegetables, cereals, pasta with vegetable broth, as well as milk soups.
• Dishes made from lean beef, poultry, boiled or baked after boiling.
• Low-fat varieties of fish (cod, pike perch, navaga, pike, carp, silver hake) boiled or steamed.
• Various types of vegetables and herbs, sour sauerkraut, ripe tomatoes.
• Crumbly semi-viscous porridges, puddings, casseroles, dishes made from oatmeal and buckwheat porridge are especially recommended.
• Eggs - no more than one per day in the form of adding to dishes, egg white omelet.
• Fruits and berries except very sour ones, compotes, jelly, lemon (with tea).
• Sugar, jam, honey.
• milk with tea, condensed, dry, low-fat cottage cheese, small amounts of sour cream, mild cheeses (Dutch, etc.). Cottage cheese and curd products are especially recommended.
• Butter, vegetable oil (up to 50 g per day).
• Tea and weak coffee with milk, non-acidic fruit and berry juices, tomato juice, rose hip decoction.

Forbidden:

• All alcoholic drinks.
• Fresh bakery products, pastry products.
• Soups with meat, fish, and mushroom broths.
• Fatty varieties of meat, poultry, fish (stellate sturgeon, sturgeon, beluga, catfish).
• Mushrooms, spinach, sorrel, radishes, radishes, green onions, pickled vegetables.
• Canned food, smoked meats, caviar.
• Ice cream, cream products, chocolate.
• Legumes, mustard, pepper, horseradish.
• Black coffee, cocoa, cold drinks.
• Cooking fats, lard.
• Cranberries, sour fruits and berries.
• Hard-boiled and fried eggs.

In case of severe vomiting, parenteral nutrition is administered, i.e. nutrients are administered intravenously. A nutritious, high-calorie diet is an important factor in the treatment of these patients.

Treatment of viral hepatitis A and E

As a rule, hepatitis A and E do not require treatment, except for severe forms of the disease. In these cases, drug treatment consists of detoxification therapy, i.e. reducing the level of toxins that accumulate in the blood due to liver damage. Usually this is the intravenous administration of various detoxification solutions.

The content of the article

Hepatitis A(synonyms for the disease: Botkin's disease, infectious, or epidemic, hepatitis) - an acute infectious disease caused by the hepatitis A virus, predominantly with a fecal-oral mechanism of infection; characterized by the presence of an initial period with an increase in body temperature, dyspeptic, flu-like symptoms, predominant liver damage, symptoms of hepatitis, metabolic disorders, and often jaundice.

Historical data of hepatitis A

For a long time, the disease was mistakenly considered catarrhal jaundice, caused by blockage of the common bile duct with mucus and swelling of its mucous membrane (R. Virchow, 1849). For the first time, the position that so-called catarrhal jaundice is an infectious disease was scientifically substantiated was expressed by S. P. Botkin (1883). The causative agent of the disease, hepatitis A virus (HAV), was discovered in 1973. S. Feinstone.

Etiology of hepatitis A

The causative agent of hepatitis A belongs to the family Picornaviridae(Italian picollo - small, small; English RNA - ribonucleic acid), a genus of enteroviruses (type 72). Unlike other enteroviruses, HAV replication in the gut has not been definitively proven. HAV is a particle with a size of 27 - 32 nm, which does not contain lipids and carbohydrates. The virus can reproduce in some primary and continuous cell cultures of humans and monkeys. The virus is resistant to environmental factors, can survive at room temperature for several months, is sensitive to formalin, concentrated solutions of chloramine and bleach, is resistant to freezing, and remains viable for two years at a temperature of -20 ° C.
Sterilization with flowing steam at a temperature of 120 ° C for 20 minutes completely inactivates infectious material.

Epidemiology of hepatitis A

The only source of infection is a sick person. The release of the pathogen into the external environment with feces begins during the incubation period, 1-3 weeks before the onset of clinical symptoms of the disease. The greatest contagiousness is observed in the first 1-2 days of the disease and stops after the 10-14th day of the disease. The pathogen is found in urine, menstrual blood, and semen, which is of less epidemiological significance.
There is no pathogen in breast milk. Often the source of infection are patients with anicteric and inparant forms of viral hepatitis A, the number of which can significantly exceed the number of patients with the manifest form. Virus carriage is not observed.
The main mechanism of infection is fecal-oral, carried out by water, food and contact-household routes. There are a large number of cases of food and water outbreaks of infection. Often group outbreaks of viral hepatitis A occur in preschool institutions and schools. There is a possibility of parenteral infection with hepatitis A during medical procedures, however, the short duration of the period of viremia makes this route of infection secondary. Sexual transmission is possible.
The susceptibility of people to infection with hepatitis A is 100%. Due to the intensive spread of the disease, most people manage to recover from the icteric or anicteric form of the infection before the age of 14. In terms of age structure, the incidence of hepatitis A is close to childhood infectious diseases (measles, scarlet fever). Adults account for approximately 10-20% of all hepatitis A cases.
Seasonality is autumn-winter, observed only among children. The periodicity of the increase in incidence with an interval of 5-5 years is typical.
Hepatitis A is a very common infection; the incidence rate depends on the state of sanitary culture and public amenities. Immunity is strong and lifelong.

Pathogenesis and pathomorphology of hepatitis A

Pathogenesis has not been studied enough. This is largely due to the lack of an adequate model of the disease and the lack of data on the replication of the pathogen. According to the scheme developed by A.F. Bluger and I. GI. Novitsky (1988), there are seven main phases of pathogenesis.
I. Epidemiological phase, or penetration of the pathogen into the human body.
II. Enteral phase. The virus enters the intestines, but it cannot be detected in the cells of the intestinal mucosa. The hypothesis that the virus multiplies in the intestines is confirmed experimentally in tamarin monkeys. According to electron morphological studies, at the onset of the disease, signs of cytolysis of varying degrees are found in enterocytes, similar to those observed in various viral infections.
III. Regional lymphadenitis.
IV. The primary generalization of infection is the penetration of the pathogen through the blood into parenchymal organs.
V. Hepatogenic phase, which begins with the penetration of the virus into the liver. There are two forms of liver damage. In one case, the changes cover the mesenchyme, hepatocytes are not damaged, and the process ends in the phase of parenchymal dissemination. In the second form, moderate damage to hepatocytes is observed. It was believed that cell damage was caused only by the cytopathic effect of the virus (CPE). However, the development of pathological changes in the liver coincides with the appearance of antibodies against the virus, and the most significant changes develop after the cessation of viral replication. It has been proven that the virus is capable of causing a strong and rapid immune response, antibodies appear even before the onset of clinical symptoms, and sensitization of immunocytes occurs early. All this gives reason to believe that the destruction of hepatocytes is largely associated with immunological processes.
VI. The phase of secondary viremia associated with the release of the virus from damaged liver cells.
VII. Convalescence phase.
Secondary viremia ends with strengthening of the immune system, liberation of the body from the virus, and the predominance of reparative processes.
Morphological changes in the case of hepatitis A are somewhat different from those observed in patients with viral hepatitis B. The characteristic morphological type of liver damage in hepatitis A is portal or periportal hepatitis. Inflammatory and alternative changes in the central zone of the hepatic lobule around the hepatic vein, as a rule, are not observed. Electron microscopic examination does not detect hepatitis A virus in liver tissue.

Hepatitis A Clinic

The following clinical forms of hepatitis A are distinguished: icteric (with cytolysis syndrome; with cholestasis syndrome), anicteric, subclinical.
The disease most often occurs in an acute cyclic form, although exacerbations, relapses, protracted course and transition to a chronic form are possible (0.3-0.5% of patients).
The following periods of illness are distinguished: incubation; initial, or pre-Zhovtyanichny; icteric; convalescence. The incubation period lasts 10-50 days, on average 15-30 days.

Jaundice form

Initial period. In most cases, the disease begins acutely. An increase in temperature (no more than 38.5 ° C) is observed within 2-3 days. Patients complain of general weakness, loss of appetite, nausea, sometimes vomiting, pain or a feeling of heaviness in the right hypochondrium and epigastric region. Upon examination, the liver and sometimes the spleen are moderately enlarged. This onset of the disease is observed in the dyspeptic variant. The flu-like variant of the initial period is characterized by short-term fever (2-3 days), short-term body aches, and sore throat.
At the end of the initial period, the urine becomes dark in color (strong tea or beer), which is due to the presence of bile pigments and precedes jaundice by 2-3 days.
The patient may complain of itchy skin. In the initial period of the disease, an important laboratory sign of viral hepatitis is an increase in the activity of serum enzymes, primarily alanine aminotransferase (ALT). The duration of the initial period is on average 3-7 days.

Jaundice period

Subictericity of the sclera indicates the end of the initial period and the transition to icteric. Jaundice reaches its maximum development within 2-3 days, after which it lasts for an average of 5-7 days. First it appears on the sclera, mucous membrane of the soft palate, frenulum of the tongue, then on the skin of the face and torso. With the development of jaundice, a significant part of the clinical manifestations of the disease characteristic of the initial period disappear, the general condition of patients improves, in most of them appetite normalizes, nausea and signs of intoxication disappear.
In most cases, the disease has a mild course, only 3-5% of patients have a moderate course. Severe form of hepatitis A is rare (1-2%). When examining the patient (palpation), attention is drawn to a further enlargement of the liver, which can be dense, sensitive, and even painful. More often than in the initial period, an enlarged spleen is detected.
During the period of increasing jaundice, the main laboratory indicator is the level of bilirubin in the blood serum. The concentration of bilirubin in the blood of patients with hepatitis A can vary widely, reaching 300-500 µmol/l in severe forms of the disease, although such high levels are rarely found. Hyperbilirubinemia is characterized by the predominant accumulation of a bound (direct, soluble) fraction of pigment in the blood, which accounts for 70-80% of its total amount. The relatively low level of free bilirubin fraction (20-30%) indicates that the function of hepatocytes regarding the binding of bilirubin with glucuronic acid is the least vulnerable, excretory function is more impaired. Impaired excretion of bilirubin into the intestines leads to discoloration of stool. Thus, clinically, disorders of pigment metabolism are manifested by jaundice, darkening of urine and discoloration of feces. Urobilinuria stops at this time, since due to acholia, urobilinogen is not produced and does not enter the blood. Jaundice gradually decreases. The first sign of renewal of the excretory function of hepatocytes is the color of stool. From this time on, the level of bilirubin in the blood serum and the intensity of jaundice decrease.
During the height of the disease, increased activity of ALT remains. Among other laboratory indicators, an increase (sometimes significant) in the thymol test and an increase in the specific gravity of gamma globulins in the blood serum should be noted. In patients with severe forms of hepatitis, hemorrhagic manifestations may appear on the skin. In these cases, disorders of the blood coagulation system are detected (decreased prothrombin index, as well as plasma concentrations of coagulation factors V, II, VI, X).
When examining blood - leukopenia with relative lymphocytosis or a normal number of lymphocytes, ESR, as a rule, does not change.
Cholestasis syndrome is not typical for hepatitis A. It is characterized by the presence of cholestasis without pronounced signs of hepatocellular failure. The duration of the cholestatic form can be C-4 months. In addition to jaundice, acholic stool, clinical signs of cholestasis include skin itching. A blood test reveals moderate leukocytosis, an increase in ESR, an increase in the activity of alkaline phosphatase, cholesterol, and beta-lipoproteins.
The anicteric form of hepatitis A includes cases of the disease without jaundice syndrome, when the blood bilirubin level does not exceed 25-30 µmol/l. Other main clinical manifestations of icteric and anicteric forms of hepatitis A are the same, but with the latter they are weaker and the duration of the disease is shorter. Changes in the blood are insignificant, except for the level of ALT activity, which increases in all clinical forms of hepatitis A.
Chronic forms of the disease are possible (0.5-1% of cases).

Complications of hepatitis A

Exacerbation and relapses are observed in 2-5% of patients. They are often associated with violations of diet and regimen, irrational use of glycocorticosteroids, the addition of intercurrent diseases, and the like. In some patients, exacerbations are manifested by deterioration of laboratory parameters (biochemical exacerbations). In case of distant relapses, the possibility of infection with viral hepatitis B must be taken into account. In such cases, testing for markers of the hepatitis B virus (HBsAg, anti-HBc) is required.
The prognosis for patients with hepatitis A is favorable.

Diagnosis of hepatitis A

The main symptoms of the clinical diagnosis of hepatitis A in all variants of the initial (pre-zhovtyanichny) period are pain or a feeling of heaviness in the right hypochondrium, sometimes itching of the skin, enlargement and sensitivity of the liver, darkening of the urine. These signs indicate damage to the liver. It is important to increase the activity of ALT in the blood serum. In the icteric period, the above symptoms are accompanied by jaundice, acholia (white feces), the content of bilirubin in the blood serum increases with a predominance of the bound (direct) fraction, and the activity of ALT increases significantly. Epidemiological data, communication with patients and a certain duration of the incubation period are taken into account. Considering that hepatitis A affects mainly children.

Specific diagnosis of hepatitis A

Specific diagnosis is based primarily on the detection of antibodies to the hepatitis A virus, which belong to class M immunoglobulins - the so-called early antibodies (anti-HAV IgM). Detection of the virus in feces in the presence of clinical signs of the disease almost stops, so scatological examination is informative when examining persons who have had contact with patients in outbreaks, especially during outbreaks in children's institutions.

Differential diagnosis of hepatitis A

In the initial (pre-zhovtyanichny) period of the disease, hepatitis A most often needs to be differentiated from influenza and other respiratory diseases, acute gastritis, and food poisoning. Hepatomegaly, pain or a feeling of heaviness in the right hypochondrium, liver sensitivity on palpation, a feeling of bitterness in the mouth, sometimes itchy skin, dark urine, splenomegaly are not observed in these diseases. Sometimes rapid enlargement of the liver with stretching of its fibrous capsule and enlargement of the lymph nodes at the porta hepatis cause a pain syndrome that resembles the clinical picture of acute appendicitis. A carefully collected medical history in most cases allows us to establish that the patient had a loss of appetite, nausea, and dark urine several days before the onset of signs of an acute abdomen. A careful examination of the patient reveals an enlargement of the liver and sometimes the spleen.
Instead of the expected leukocytosis, a normal number of leukocytes or leukopenia with relative lymphocytosis is observed. Epidemiological history data are of great importance.
Determining the level of serum alanine aminotransferase activity helps to establish the diagnosis of hepatitis A in the initial period of the disease or in the case of anicteric form.
During the icteric period of viral hepatitis, it is necessary to find out the origin of the jaundice.
Prehepatic jaundice is caused by increased hemolysis of red blood cells (hemolytic jaundice) and the accumulation of unbound (indirect, insoluble) bilirubin fraction in the blood, which indicates against viral hepatitis. In such persons, unlike patients with viral hepatitis, the level of ALT does not increase, the color of urine does not change, and acholia does not occur - the feces are intensely colored.
Differentiating subhepatic (obstructive) jaundice from the cholestatic form of viral hepatitis can cause significant difficulties. In such cases, a thorough analysis of the characteristics of the pre-zhovtyanichny period helps to clarify the diagnosis; in case of hepatitis it has quite pronounced signs, but in the case of subhepatic (obstructive) jaundice there are none. Clinically, the possibility of subhepatic jaundice is indicated by an earthy-gray skin tone, intense itching, and sharp abdominal pain.
Often the development of jaundice is preceded by attacks of biliary colic or acute pancreatitis. Examination of the patient is of great importance - the presence of Courvoisier's symptom, local muscle tension, Ortner's symptom, etc. If jaundice is caused by cholelithiasis, fever, chills, leukocytosis, and an increase in ESR are often observed.
The differential diagnosis of viral hepatitis with cancer of the major duodenal papilla is quite difficult. In these cases, jaundice is often preceded by prolonged itching of the skin, while the mouth of the common bile duct and pancreatic duct is only partially blocked. In such patients, the manifestation of pancreatitis and cholangitis is possible, jaundice has an alternating character (an important sign of this pathology).
In all forms of obstructive jaundice, bilirubin testing has no differential diagnostic value. More attention is deserved by determining the activity of ALT in the blood serum, which in this form of jaundice is normal or slightly increased, while in viral hepatitis it is significantly increased. Of auxiliary importance is the ratio of transaminases - AST / ALT. In patients with viral hepatitis, the activity of ALT predominantly increases, so this coefficient is less than one, in case of obstructive jaundice it is more than one. The activity of alkaline phosphatase in viral hepatitis is normal or moderately increased, and in obstructive jaundice it increases significantly. However, with the cholestatic form of viral hepatitis, the activity of the enzyme in the blood serum increases markedly, and therefore its differential diagnostic value decreases. In difficult cases, special instrumental (including endoscopic), ultrasound, duodenography, and, if necessary, laparoscopy are used.
Viral hepatitis is differentiated from chronic hepatitis and liver cirrhosis on the basis of the clinical characteristics of the disease and laboratory parameters - duration of the course, signs of portal hypertension, profound disorders of protein metabolism, decreased albumin synthesis, an increase in the amount of gamma globulins of more than 30%, the presence of similar liver signs. In complex cases, a liver scan is of diagnostic value.
Jaundice can develop with infectious diseases such as infectious mononucleosis, leptospirosis, cytomegalovirus disease, toxoplasmosis, pseudotuberculosis, etc. Leptospirosis, for example, is characterized by an acute onset, fever, pain in the calf muscles, kidney damage, hemorrhagic syndrome, scleritis, leukocytosis and a significant increase in ESR; infectious mononucleosis is characterized by sore throat, polyadenitis, leukocytosis, and the presence of atypical mononuclear cells in the blood. Pseudotuberculosis is characterized by an acute onset, pain in the area of ​​the appendix, a clinical picture of mesadenitis, symptoms of socks, gloves, cuffs, various rashes, including scarlet fever.
Differential diagnosis of hepatitis A with other types of viral hepatitis (B, C, E) is carried out using specific research methods. Epidemiological data are taken into account.

Treatment of hepatitis A

Treatment of patients with mild and moderate forms of hepatitis A does not require the use of drugs. The basis of treatment is sufficient basic therapy, a gentle regime in the acute period - bed rest and diet No. 5, which provides for the exclusion of fatty, smoked, pickled foods, fried foods, canned food, meat broths, sour cream, etc. from the patient’s diet. The consumption of foods is prohibited containing refractory fats (for example, lard), strong tea, coffee, cocoa and all types of alcohol. Low-fat cheese, vegetarian and dairy soups, oatmeal, semolina, buckwheat, rice porridge, kefir, yogurt, pasta, low-fat meat and fish are recommended. It is allowed to consume vegetable fats and butter within the limits of physiological need. To enrich the diet with vitamins, berries, fruits, vegetables (beets, carrots, cabbage) in grated form, as well as compotes, jelly, mousses and jellies from juices are recommended. Food should be prepared without salt (limited during meals), in grated form, meat (in the form of minced meat) is steamed. The amount of fluid should exceed the physiological need by 30-40%. Of the choleretic drugs in the acute period, it is advisable to prescribe only sorbitol and magnesium sulfate, which, without increasing the production of bile, promote its outflow due to osmotic action and the release of the hormone cholecystokinin. You need to make sure that you have bowel movements every day.
If necessary, detoxification and infusion therapy are used. In case of significant intoxication, a 5-10% glucose solution with the addition of ascorbic acid is administered.
Patients are discharged from the hospital according to clinical indications, after complete normalization of pigment metabolism.

Clinical examination

A month after discharge, the patient is examined in the infectious diseases hospital where he was treated. If the biochemical parameters are normal, the patient further requires observation by a CIZ doctor or gastroenterologist, or a local doctor at the place of residence with a re-examination after 3 and 6 months.
In case of residual effects of viral hepatitis, the patient is subject to monthly outpatient supervision by a doctor at an infectious diseases hospital, and, if indicated, hospitalization.

Prevention of hepatitis A

Patients are hospitalized and sometimes isolated at home under the supervision of an epidemiologist. Basic sanitary and epidemiological measures to prevent the fecal-oral spread of infection.
Surveillance of persons who were in contact with patients in outbreaks is carried out for 35 days. In children's institutions, quarantine is established for 35 days; within two months after the last case of hepatitis A, routine vaccinations are not carried out. Prevention of viral hepatitis A involves the administration of immunoglobulin according to epidemiological indications (intensity of incidence) in the most susceptible age groups of the population: children from 1 to 6 years old - 0.75 ml, 7-10 years old - 1.5 ml, over 10 years old and adults - 3 ml.

Viral hepatitis A is an acute, cyclical disease characterized by short-term symptoms of intoxication, transient disorders of liver function, and a benign course.

In childhood, HAV accounts for up to 85% of all registered cases of viral hepatitis.

Etiology. Hepatitis A virus (HAV) was discovered by S. Feinstone (1973). The virus is a spherical RNA-containing particle with a diameter of 27 nm (Fig. 39). The central part of the virus is represented by the nucleocapsid, the outer part has a two-layer shell consisting of protein capsomers. The properties of the virus are similar to enteroviruses. Localized in the cytoplasm of hepatocytes. Insensitive to ether, but quickly inactivated by formaldehyde solutions and UV irradiation; at a temperature of 100° C it is inactivated within 5 minutes. It is found in feces in the initial (pre-icteric) period of the disease; with the appearance of jaundice, the excretion of the virus quickly decreases. Experimental models of HAV are monkeys and chimpanzees. The possibility of cultivating virus A in transplanted human liver tissue has been proven.

Epidemiology . HAV is common in all countries of the world. The incidence can be sporadic or in the form of epidemic outbreaks. In different regions of our country, incidence rates are not the same. The highest incidence is in the republics of Central Asia.

In the overall structure of the incidence of HAV, children account for more than 70%. Children aged 3 to 7-10 years are most often affected. Petya is practically never sick in life due to the immunity received transplacentally from the mother.

The source of infection is only a sick person. The greatest epidemiological danger is posed by patients with erased, anicteric and inapparent forms.

The virus is found in patients' blood, feces and urine. Its appearance in feces is noted long before the first clinical symptoms, but the highest concentration occurs in the pre-icteric period. In the first days of the jaundice period, the virus can be detected in the blood and feces of no more than 10-15% of patients, and after the 4-5th day from the onset of jaundice - only in isolated cases.

Viral hepatitis A is a typical intestinal infection. Transmission of the virus occurs mainly through household contact, as well as through food and water. Mechanical transmission can be carried out by flies. Transmission of infection by airborne droplets is allowed. However, if such a path occurs, it is apparently very rare. Transplacental transmission of hepatitis A virus has not been proven. Susceptibility to the virus is extremely high. Among the adult population, antibodies to the hepatitis D virus are found in 70-80%, which proves the widespread prevalence of infection among people.

The highest incidence of HAV is recorded in the autumn-winter period (September-January), the lowest - in the summer period (July-August). Epidemic outbreaks of diseases are usually observed in children's institutions.

After suffering from HAV, stable, lifelong immunity is formed. Recurrent diseases are rare - in 1-5% of children. In these cases, infection with another type of hepatotropic virus cannot be ruled out.

Pathogenesis. After infection through the fecal-oral route, the virus from the intestine hematogenously enters hepatocytes, where it finds optimal conditions for reproduction. The direct mechanisms leading to damage to hepatocytes have not been fully established. A direct cytopathic effect of the virus is allowed; in this case, the initial link of the pathological process in HAV is the penetration of the virus into the hepatocyte and its interaction with biological macromolecules taking part in detoxification processes. The consequence of this interaction is the release of free radicals, which act as initiators of lipid peroxidation processes in cell membranes. The intensification of lipid peroxidation processes leads to a change in the structural organization of lipid components of membranes due to the formation of hydroperoxide groups, which causes the appearance of “holes” in the hydrophobic barrier of biological membranes and, consequently, an increase in their permeability. A central link in the pathogenesis of IAV appears - cytolysis syndrome. It becomes possible for biologically active substances to move along a concentration gradient. Since the concentration of enzymes inside heiatocytes is tens and even hundreds of thousands of times higher than their content in the extracellular space, the activity of enzymes with cytoplasmic, mitochondrial, lysosomal and other localization increases in the blood serum, which indirectly indicates a decrease in their content in intracellular structures, and therefore, to a reduced bioenergetic regime of chemical transformations. Replacement of intracellular potassium increases damage to oxidative phosphorylation and contributes to the development of intracellular acidosis.

The changed reaction of the environment in hepatocytes and the disruption of the structural organization of subcellular membranes lead to the activation of acid hydrolases (RNase, cathepsins, leucine aminopeptidase, etc.), which is to a certain extent facilitated by a decrease in the activity of the tissue proteinase inhibitor α 2 -macroglobulin.

The final action of proteolytic enzymes is the hydrolytic breakdown of necrotic hepatocytes with the release of protein complexes, which can act as autoantigens and, along with the hepatotropic virus, stimulate the T- and B-system of immunity, activating, on the one hand, hypersensitized killer cells, and on the other - causing the formation of specific anti-hepatic antibodies that can attack the liver parenchyma. However, the mechanism of autoimmune aggression in HAV is not fully realized, therefore severe forms of this type of hepatitis do not occur. Thus, the pathological process with HAV goes through a number of successive interdependent stages with the obligatory participation of the virus itself and the inclusion of the liver in the immunopathological process.

The pathomorphology of IAV was studied using liver puncture biopsy material, since there are practically no lethal outcomes. The pathological process in the liver begins several days before the appearance of the first clinical symptoms of the disease with the activation and proliferation of stellate reticuloendotheliocytes (Kupffer cells), as well as mononuclear infiltration mainly along the portal tracts. Changes in hepatocytes occur at the end of the prodromal period. Initially, the nucleoli enlarge, numerous mitoses occur, and protein dystrophic changes appear in hepatocytes, mainly in the peripheral zone of the acini.

At the height of clinical manifestations, the phenomena of balloon degeneration increase and scattered necrosis of hepatocytes appears. The latter undergo autolytic breakdown or can mummify, turning into eosinophilic bodies similar to Councilman's bodies. In areas of scattered necrosis, cellular lymphohistiocytic infiltration occurs, which, along with increased inflammatory infiltrates along the portal tracts, disrupts the structure of the hepatic parenchyma and causes discomplexation of its beam structure. Simultaneously with the processes of dystrophy and necrobiosis, regeneration occurs. As clinical manifestations decline, the number of dividing cells increases, and the reticulin stroma of the parenchyma becomes coarser. Cellular infiltration gradually decreases. The process usually ends at 6-8 weeks of illness, but can drag on for up to 4-5 months of illness, ending with complete restoration of the functional state of the liver. Chronic hepatitis does not develop; residual fibrosis is possible.

Clinical picture . In the typical course of the disease, cyclicity is clearly expressed with a sequential change of four periods: initial, or prodromal (pre-icteric), peak (icteric), post-icteric and the period of convalescence.

The incubation period for HAV is from 10 to 45 days, with an average of 15-30 days. During this period, there are no clinical manifestations of the disease, however, the virus and high activity of liver cell enzymes (AlAT, AST, F-1-FA, etc.) can already be detected in the blood.

• Initial (prodromal) period [show]

  The disease, as a rule, begins acutely with a rise in body temperature to 38-39 ° C, less often to higher numbers and the appearance of symptoms of intoxication: malaise, weakness, headache, loss of appetite, nausea and vomiting. Characteristic pain is in the right hypochondrium, in the epigastrium or without a specific localization. Usually the pain is dull, there is a feeling of heaviness or pressure in the right hypochondrium, but sometimes the pain can be of an acute paroxysmal nature, creating the impression of an attack of acute appendicitis, acute cholecystitis and even cholelithiasis. Children become capricious, irritable, lose interest in games and studies, and have trouble sleeping. Transient dyspeptic disorders often occur: flatulence, constipation, and less commonly, diarrhea. In rare cases, mild catarrhal symptoms are possible in the form of nasal congestion, hyperemia of the pharynx, and slight coughing.

  After 1-2 days, less often 3 days from the onset of the disease, the body temperature normalizes and the symptoms of intoxication weaken somewhat, but general weakness, anorexia, nausea still persist, vomiting occurs, and abdominal pain intensifies. The most important objective symptom is an increase in the size of the liver, sensitivity and pain on palpation. This symptom is detected in all patients from the first days of the disease; in a third of cases the spleen is palpable. By the end of the pre-icteric period, as a rule, darkening of the urine (the color of beer) is observed; less often, partial discoloration of feces (the color of clay) occurs.

  Of the laboratory tests, the appearance of hyperenzymemia is important in this period. The activity of all hepatic cellular enzymes (AlAT, AST, F-1-FA, sorbitol dehydrogenase, glutamate dehydrogenase, urocaninase, etc.) is sharply increased. The thymol test and the amount of β-lipoproteins also increase, and dysproteinemia is detected due to an increase in the gamma globulin fraction. The total amount of bilirubin at the onset of the disease has not yet increased, but it is still often possible to detect an increased content of the bound (direct) fraction. From the very first days of illness, the amount of urobilin in the urine increases; and at the end of the pre-icteric period bile pigments are detected.

  The duration of the prodromal (pre-icteric) period with HAV is 3-5 days) rarely extended to 7 days or shortened to 1-2 days.

• High period (icteric period) [show]

  Jaundice usually appears on the 3-5th, less often on the 6-7th day of illness.

  With the appearance of jaundice, the condition improves, and intoxication disappears in many patients. First, yellowness of the sclera appears, and then the skin of the face, torso, hard and soft palate, and later of the extremities. Jaundice grows quickly, over 2-3 days; often the patient turns yellow as if “overnight.”

  In terms of intensity, jaundice with HAV can be mild or moderate and lasts for 7-10 days. Jaundice persists for the longest time in the folds of the skin, ears, and especially on the sclera in the form of marginal icterus of the sclera.

  At the height of jaundice, the size of the liver is maximally increased. The edge of the liver becomes denser, rounded, and painful on palpation. The enlargement of the liver is mostly uniform, but often one left lobe is more enlarged. The size of the spleen during this period of the disease is increased in half the cases. In this case, the edge of the spleen is palpated with moderate density, sometimes sensitive.

  At the height of jaundice, the urine is maximally saturated, and the feces are discolored. However, the degree of change in the color of excrement depends solely on the level of bilirubin in the blood serum, and, consequently, on the severity of icteric staining of the skin.

  Changes in other organs with CAA are mild. One can only note moderate bradycardia, a slight decrease in blood pressure, weakening of heart sounds, impurity of the first tone or a slight systolic murmur at the apex, a slight emphasis of the second tone on the pulmonary artery, short-term extrasystoles are detected.

  At the height of clinical manifestations, urine is maximally saturated or dark-colored (especially foam), and its amount is reduced. Often traces of protein, single red blood cells, hyaline and granular casts are found in the urine.

  During this period, liver tests changed as much as possible. In the blood serum, the content of bilirubin is increased almost exclusively due to the bound (direct fraction), the activity of hepatic cellular enzymes (ALAT, AST, F-1-FA, etc.) is increased, changes in other types of metabolism are increasing.

  Hematological changes are insignificant. In the blood, normocytosis or moderate leukopenia with relative neutropenia, monocytosis and lymphocytosis is more common. At the height of intoxication, plasma cells appear in small numbers in the blood. ESR is always within normal limits.

• Post-icteric period [show]

  Almost immediately after reaching the maximum level (usually on the 7-10th day from the onset of the disease), jaundice begins to disappear. This is accompanied by the complete disappearance of intoxication symptoms, improved appetite, a significant increase in diuresis (polyuria), bile pigments disappear in the urine and urobilin bodies appear, and stool becomes colored. In the normal course of the disease, the period of decline in clinical manifestations occurs within 7-10 days. After this, the third, post-icteric, period begins. It is characterized by a relatively slow decrease in liver size. Children feel quite healthy, but in addition to the enlarged size of the liver and sometimes the spleen, their liver function tests remain pathologically altered.

• Fourth recovery period, or convalescence period [show]

  The period of convalescence in most children is characterized by normalization of the size of the liver, restoration of its functional state and a completely satisfactory condition of the child. In some cases, children complain of rapid fatigue after physical activity, abdominal pain, sometimes there is a slight increase in the size of the liver, dysproteinemia, episodic or constant slight increases in enzyme activity. These symptoms are observed in isolation or in various combinations. The duration of the convalescence period is about 2-3 months.

Classification . CAA is classified by type, severity and course (Table 15).

Typical cases include all cases accompanied by the appearance of icteric staining of the skin and visible mucous membranes. Among them, mild, moderate and severe forms are distinguished by severity, while all atypical cases (anicteric, erased, subclinical) are not divided by severity, since they are always regarded as mild forms of the disease.

The severity (form) of the disease is assessed in the initial period, but not before the clinical symptoms characteristic of viral hepatitis develop, and the manifestations of the initial (pre-icteric) period are also taken into account. When assessing severity, the severity of general intoxication, jaundice, as well as the results of biochemical studies are taken into account.

• Light form [show]

  The mild form is characterized by a moderate increase in body temperature or low-grade fever, mild manifestations of intoxication, minor subjective complaints during the height of the disease, and a moderate increase in liver size.

  In the blood serum, the content of total bilirubin does not exceed 85 µmol/l (with a norm of up to 17 µmol/l), and free bilirubin - 25 µmol/l (with a norm of up to 15 µmol/l), the value of the prothrombin index is at the borderline of normal, the thymol test is moderate increased, the activity of hepatocellular enzymes exceeds the norm by 5-10 times.

• Moderate form [show]

  The moderate form is manifested by moderately severe symptoms of intoxication. In the prodromal period, the body temperature in most patients rises to 38-39 ° C, and lethargy, dyspeptic symptoms, and abdominal pain are characteristic. With the appearance of jaundice, although the symptoms of intoxication weaken, general lethargy, anorexia, often nausea, and single vomiting are still possible within 2-3 days. In the blood serum, the level of total bilirubin is within the range of 85-200 µmol/l. including free (indirect) up to 50 µmol/l. The prothrombotic index is often reduced (up to 70-60%) and the thymol test is significantly increased. The activity of hepatocellular enzymes is high.

• Severe form [show]

  Severe form of HAV is rare. In this form, the phenomena of general intoxication become more pronounced and jaundice is pronounced. The symptoms of the initial (prodromal) period are not much different from the moderate form of the disease. Characterized by vomiting, lethargy, and anorexia. Differences begin to emerge from the first days of the icteric period. In severe forms with the appearance of jaundice, the symptoms of intoxication not only do not subside, but may even intensify. Apathy, lethargy, anorexia, dizziness, repeated vomiting, bradycardia, nosebleeds, hemorrhagic rashes, and a significant decrease in diuresis are noted. The bilirubin content in the blood serum is more than 170-200 µmol/l. At the same time, the level of free (indirect) bilirubin is above 50 µmol/l, the prothrombin index decreases to 40%, the thymol test indicators increase significantly, and the activity of hepatocellular enzymes increases sharply.

• Anicteric form [show]

  In the anicteric form, the patient has no icterus of the skin and sclera upon systematic observation. The remaining symptoms do not differ from those of the icteric form. In this case, the patient may experience a short-term increase in body temperature, loss of appetite, lethargy, weakness, nausea and even vomiting. These symptoms are observed only in the first days of the disease and last no more than 3-5 days. The leading symptom is an increase in the size of the liver with thickening of its consistency and pain on palpation. The spleen may become enlarged, and sometimes dark urine and discolored stool may occur for a short period of time. Increased activity of AlAT, AST, F-1-FA and other hepatocellular enzymes is always detected in the blood serum; increased levels of thymol test and β-lipoproteins. Often in the blood serum there is a short-term and slight increase in the amount of bound bilirubin (up to 20-40 µmol/l).

• Erased form [show]

  The erased form is characterized by mildly expressed main symptoms of the disease, including slight yellowing of the skin and sclera, which disappears after a few days. In the erased form, the symptoms of the prodromal (initial) period are not clearly expressed. Often absent, but sometimes there may be increased body temperature, lethargy, weakness, and loss of appetite. At the time of the appearance of jaundice, symptoms of intoxication are completely absent, the size of the liver is slightly increased. Dark urine and discolored feces appear with great consistency, but for a short time. Clinical manifestations and features of the course of the erased form can be characterized as a lightweight, rudimentary version of the mild typical form. Its significance, like the anicteric form, lies in the difficulty of recognition, and, consequently, in the untimeliness of anti-epidemic measures.

• Subclinical (inapparent) form [show]

  The subclinical (inapparent) form, in contrast to the erased and anicteric forms, is characterized by a complete absence of clinical manifestations. The diagnosis is established only by biochemical examination of children who are in contact with patients with viral hepatitis. The greatest importance for the diagnosis of such forms is an increase in the activity of enzymes (AlAT, AST, F-1-FA, etc.); the thymol test is less often positive. This diagnosis is reliably confirmed by the detection of IgM class antibodies to the hepatitis A virus in the blood serum. There is reason to believe that in the focus of HAV infection, most children carry inapparent forms, which, while remaining undetected, support the epidemic process.

Course and outcomes . The course of CAA may be

• sharp [show]

  An acute course occurs in the vast majority of children. The disappearance of clinical symptoms and normalization of biochemical parameters occur 1-3 months from the onset of the disease. There are cases with particularly rapid disappearance of clinical symptoms, when by the end of the 2-3rd week of the disease there is a complete clinical recovery and the functional state of the liver is normalized, but there may also be a slower reverse dynamics of clinical manifestations with a slower rate of restoration of liver function.

• protracted [show]

  With a protracted course of CAA, the reverse dynamics of clinical manifestations and normalization of biochemical changes are significantly delayed, occurring only within 3 to 6 months from the onset of disease. In this case, icteric staining of the skin may remain for a longer time, but more often the clinical symptoms remain an enlarged, dense and painful liver, and less often, an enlarged spleen. Particularly typical for protracted forms are a persistent, albeit moderate, increase in the activity of hepatic cellular enzymes, an increase in the thymol test, β-lipoproteins, and the phenomenon of dysproteinemia.

With a protracted, less often acute, course of CAA, exacerbations may occur; At the same time, against the background of a decline in clinical symptoms and normalization of liver function tests, an increase in jaundice, an increase in liver size and a deterioration in liver function tests are again noted. However, regardless of the nature of the course and the duration of the recovery period, CAA ends with complete recovery.

In rare cases, after the completion of the convalescence period, the child remains with slight hepatomegaly as a result of liver fibrosis in its normal functional state or damage to the biliary tract is detected, most often in the form of dyskinesia.

Diagnosis. The diagnosis of HAV in typical cases is not difficult. It is based on the combination of an acute onset of the disease with a short-term increase in body temperature, symptoms of intoxication, an increase in the size of the liver, the appearance of pain and hardening on palpation, jaundice, dark urine, discolored feces, rapid reverse development of the main symptom complex and a favorable course of the disease. For diagnosis, the presence of repeated diseases in a team or family after a short incubation period, the lack of information about blood transfusions and blood products, as well as other parenteral interventions over the last 4-5 months are important.

Of the laboratory nonspecific methods, the most important is the determination of the activity of hepatocellular enzymes in the blood serum. In all forms of HAV, high rates of cytoplasmic (AlAT, AST, F-1-FA, LDH, etc.), mitochondrial (GLDH, urocaninase, MDH, etc.) and lysosomal (RNase, LAP, etc.) activity are detected in the blood serum. enzymes. High levels of thymol test, β-lipoproteins and immunoglobulin M are also characteristic.

Of the specific methods, the detection of antibodies against the virus belonging to the IgM class (anti-HAV IgM) in the blood serum is crucial (Fig. 40), as well as the detection of virus particles in feces using electron microscopy.

Differential diagnosis

• ARVI [show]

  In the pre-icteric period, HAV most often has to be differentiated from ARVI. It is important to take into account that catarrhal symptoms are not typical for viral hepatitis. Rarely, slight coughing, swelling and hyperemia of the mucous membranes of the nasopharynx occur, but they never dominate the clinical picture of the disease. ARVI is not characterized by an increase in the size of the liver and there is never significant thickening or pain. The appearance of dark-colored urine and discolored stool makes the diagnosis of CAA much easier.

• Appendicitis [show]

  Acute abdominal pain in the prodromal period of CAA sometimes simulates appendicitis. In contrast to appendicitis, with CAA, palpation of the lower half of the abdomen is painless, the abdomen is soft, only pain is noted in the liver area. Tension of the rectus abdominis muscles and symptoms of peritoneal irritation, which is characteristic of appendicitis, are not detected.

  Changes in the blood are of great diagnostic importance. With HAV, there is a tendency to leukopenia and lymphocytosis, while with acute appendicitis, neutrophilic leukocytosis and increased ESR are noted.

• Helminthic intoxication [show]

  In some cases, the pre-icteric period in patients with HAV is mistaken for helminthic intoxication. But with helminthic infestation, complaints last for several weeks and even months, while the pre-icteric period rarely lasts longer than 7 days.

In the differential diagnosis of viral hepatitis in the icteric period, it seems especially important at the first stage to answer the question of what type of jaundice (suprahepatic, hepatic, subhepatic) one is dealing with.

• Prehepatic jaundice [show]

  Prehepatic jaundice occurs as a result of increased hemolysis of red blood cells and excessive formation of free bilirubin. Upon further examination of such a child, one can note pronounced pallor of the skin and mucous membranes, a significant increase in the size of the spleen (the size of the liver is not increased), moderate jaundice even during a crisis. Urine often remains light or slightly saturated due to an increase in the amount of urobilin; bile pigments are not detected. The color of stool is dark brown due to the high content of urobilinogen in it. The concentration of free bilirubin in the blood serum is increased. Other biochemical parameters (activity of hepatocellular enzymes, thymol test, prothrombin index) were not changed. In the blood there is a decrease in the level of hemoglobin and red blood cells, high reticulocytosis.

• Hepatic jaundice [show]

  Hepatic jaundice can occur due to a violation of the function of uptake, conjugation or excretion of bilirubin by liver cells. In cases where the function of bilirubin uptake is predominantly impaired, the clinical picture is characteristic of Gilbert's syndrome. The disease manifests itself as indirect hyperbilirubinemia, usually occurs during puberty and is characterized by a benign course.

  Hereditary hepatoses also include Labigne-Johnson and Rotor syndrome, in which a violation of pigment metabolism occurs at the stage of bilirubin excretion by hepatocytes. Predominantly conjugated (direct) bilirubin accumulates in the blood serum. But there are no disturbances in other liver functions and normal enzyme activity levels are noted.

  In the icteric period, CAA often has to be differentiated from angiocholecystitis, in which the most typical complaints are paroxysmal or aching abdominal pain, especially in the right hypochondrium, recurrent nausea and vomiting, and intolerance to fatty foods. Angiocholecystitis is also characterized by prolonged low-grade fever, leukocytosis, neutrophilia, and increased ESR, while the activity of hepatocellular enzymes usually remains normal.

Treatment. All patients with HAV, regardless of severity, must remain in bed throughout the entire acute period until the symptoms of intoxication disappear. The criterion for expanding the regimen is an improvement in well-being and appetite, a decrease in jaundice, an increase in diuresis, a decrease in the level of bilirubin in the blood serum, enzyme activity, etc.

The diet is complete, easily digestible, and, if possible, physiological. The ratio of proteins, fats and carbohydrates is 1:1:4-5. Long-term restriction of animal proteins and a sharp reduction in fats in the child’s diet are not indicated.

If there are symptoms of intoxication, most of the daily protein intake is administered with dairy and vegetable products. The lack of protein in this period can be compensated by the administration of cottage cheese. Children under 3 years old are prescribed 50-100 g of cottage cheese, older ones - 200-300 g daily. As the symptoms of intoxication decrease, the diet should be age-appropriate; a sufficient amount of lean meat, fish, and eggs is introduced into the diet. For the entire acute period of the disease, extractive substances, smoked meats, marinades, refractory fats, and spices should be excluded from the diet. At the same time, small amounts of sauerkraut, pickled cucumbers, green onions, red or black caviar, and lightly salted herring are allowed. The amount of fat in children is somewhat limited in the first days of the disease, until the first signs of improvement appear. Subsequently, fats are prescribed in quantities appropriate to the child’s age. Usually they give butter and vegetable oil. Other types of fats are not used in the diet.

Throughout the entire icteric period, choleretic drugs are given orally (immortelle decoction, corn silk, berberine, flamin, choleretic collection, etc.). It is advisable to prescribe B vitamins (B1, B2, B6), vitamins C and PP orally.

All patients with mild forms and most with moderate forms do not require additional drug treatment. In case of HAV, only in severe cases for the purpose of detoxification, rheopolyglucin, hemodez, and 10% glucose solution are administered intravenously (total volume up to 500 ml per day). Corticosteroids are not prescribed for CAA.

For a prolonged course of the disease, treatment is the same as for an acute one. In particularly stubborn cases, you can carry out a course of treatment with Essentiale, 1 capsule 3 times a day for 1-1.5 months, and prescribe Legalon, 1 tablet 3 times a day for 20-30 days.

As agents that increase the bioenergetic potential of hepatocytes, in case of prolonged CAA, cocarboxylase can be prescribed in a dose of 0.025-0.05 g once a day intramuscularly, vitamin B5 in a dose of 50-100 mg intramuscularly every other day.

Prescribing corticosteroids for prolonged CAA is also undesirable. Only in rare cases, with high activity of the pathological process and especially in combination with severe long-term hyperbilirubinemia, can corticosteroids be prescribed in a short course (no more than 7-10 days) at the rate of 1-2 mg of prednisolone per 1 kg of child’s body weight per day for 3-4 days followed by rapid dose reduction.

Discharge from hospital and follow-up . Patients with HAV are discharged from the hospital as they recover (15-20 days of illness). The criteria for discharge are: satisfactory general condition, absence of jaundice, a clear reduction in liver size in the presence of normal serum bilirubin and hepatocellular enzyme activity. A persistent isolated increase in liver size (no more than 2 cm below the costal margin) or a moderate increase in enzyme activity (no more than 2-4 times higher than normal values) is not a contraindication for discharge from hospital.

Since the course of CAA is almost always favorable, it is possible to treat patients with mild forms of CAA at home.

After discharge from the hospital, all children are subject to dispensary observation. It is better to carry out clinical examination in a special room organized at the hospital. If it is impossible to organize such an office, medical examination should be carried out by a local pediatrician in a children's clinic. The first examination and examination of the child is carried out 15-30 days after discharge from the hospital, repeated - after 3 months. In the absence of residual clinical effects and complete normalization of biochemical samples, convalescents can be removed from the register. In those cases where there are any residual effects, clinical observation continues until complete recovery.

Prevention . Patients with HAV pose the greatest epidemiological danger in the very initial - pre-icteric period, therefore a system of measures aimed at early diagnosis and timely isolation of the patient is decisive in preventing the spread of diseases in the environment. When the first case of the disease appears in a children's institution, the group is quarantined for 35 days from the date of isolation of the sick person; during this period, the transfer of children to other institutions is prohibited. Admission of new children who have not previously had viral hepatitis is allowed only after the administration of immunoglobulin.

After the isolation of the first sick person, all contact children are subject to careful clinical observation for the entire quarantine period. Children from quarantine groups who show signs of illness (fever, lethargy, loss of appetite, unclear gastrointestinal phenomena, etc.) are isolated from the group and examined (enzyme activity, bile pigments in the urine, etc.). If it is impossible to examine a child suspected of HAV at home, it is necessary to hospitalize him in the diagnostic department. In places where the patient is isolated (in the hospital or at home), the same regime is observed as for other intestinal infections, and a disinfection system is carried out according to the instructions.

For the prevention of HAV, immunoglobulin is used for epidemic indications. Children from 1 year to 10 years are administered 1 ml, older age groups - 1.5 ml. The greatest preventive effect is observed when immunoglobulin is administered to all contact children immediately (no later than 5-6 days) after the occurrence of the first case of the disease. Active immunization is being developed.

Source: Nisevich N. I., Uchaikin V. F. Infectious diseases in children: Textbook. - M.: Medicine, 1990, -624 p., ill. (Educational literature for student medical institute, pediatric faculty.)