Hepatitis A - Symptoms

Symptoms of hepatitis A are characterized by a wide range of clinical signs: from inapparent subclinical forms, occurring without clinical symptoms, to clinically expressed forms with pronounced symptoms of intoxication and rather severe metabolic disorders.

In the typical course of the disease, there is a distinct cyclicity with a sequential change of four periods: incubation, pre-icteric, icteric and post-icteric. Considering that anicteric forms are often encountered, it is more correct to distinguish the following periods of the disease: incubation, prodromal, or initial (pre-icteric), the peak period (full development of the disease) and the recovery period. The division into periods is to a certain extent schematic, since the boundary between them is not always clear. In some cases, the initial (prodromal) period may be unexpressed, and the disease begins as if immediately with jaundice. The allocation of the incubation period is very important, since its precise delimitation allows for preliminary differentiation of hepatitis A from hepatitis B; the study of the initial period determines the possibility of early diagnosis of the disease, precisely at the time when the patient is most contagious.

The period of convalescence, in accordance with its essence, can also be called restorative or reparative. This emphasizes its great clinical significance, since recovery from hepatitis A, although inevitable, still occurs in several stages and has several options.

From a pathogenetic point of view, the incubation period corresponds to the phase of parenchymatous diffusion and hepatic replication of the virus; the initial (prodromal) period - the phase of generalization of the infection (viremia); the peak period - the phase of metabolic disorders (liver damage); the convalescence period - the phase of persistent reparation and elimination of the virus.

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The first signs of hepatitis A

The incubation period for hepatitis A is from 10 to 45 days. Apparently, only in rare cases can it be shortened to 8 days or extended to 50 days. During this period, no clinical manifestations of the disease are observed. However, the activity of liver-cell enzymes (ALT, ACT, F-1-FA, etc.) increases in the blood and the hepatitis A virus is detected in free circulation. These data are of great practical importance, since they substantiate the advisability of conducting serum tests for the level of these enzymes in hepatitis A foci if this disease is suspected.

The disease usually begins acutely with a rise in body temperature to 38-39 C, less often to higher values, and the appearance of intoxication symptoms (malaise, weakness, loss of appetite, nausea and vomiting). From the first days of the disease, patients complain of fatigue, headache, bitter taste and bad breath, a feeling of heaviness or pain in the right hypochondrium, epigastrium or without a specific localization. The pain is usually dull or colicky. It can be strong and create the impression of an attack of appendicitis, acute cholecystitis and even cholelithiasis. A noticeable change in mood is characteristic of the prodromal period, expressed in irritability, increased nervousness, capriciousness, sleep disturbance. In 2/3 of patients in the pre-icteric period of the disease, repeated vomiting is noted, not associated with the intake of food, water and medicines, less often vomiting is multiple. Transient dyspeptic disorders often occur: flatulence, constipation, and, less commonly, diarrhea.

In rare cases (10-15%), catarrhal symptoms such as nasal congestion, hyperemia of the mucous membranes of the oropharynx, and slight coughing are observed in the initial period. These patients, as a rule, have a high temperature reaction. Until recently, catarrhal symptoms in hepatitis A were attributed to the underlying disease, which gave some authors grounds to distinguish a flu-like variant of the pre-icteric period. According to modern concepts, the hepatitis A virus does not affect the mucous membranes of the oropharynx and respiratory tract. The occurrence of catarrhal symptoms in some patients in the initial period of hepatitis A should be regarded as manifestations of an acute respiratory viral disease.

After 1-2, 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, vomiting and usually increased abdominal pain still persist.

The most important objective symptoms in this period of the disease are an increase in the size of the liver, its sensitivity and pain upon palpation. An increase in the size of the liver is observed in more than half of the patients and from the first days of the disease, in isolated cases the edge of the spleen is palpated. The liver usually protrudes from under the edge of the costal arch by 1.5-2 cm, of moderate density,

By the end of the pre-icteric period, as a rule, darkening of urine is observed (the color of beer in 68% of patients), less often - partial discoloration of feces (the color of clay in 33%). In some patients, the clinical manifestations of the initial period are weakly expressed or absent altogether, and the disease begins as if immediately with a change in the color of urine and feces. This variant of the onset of hepatitis A occurs in 10-15% of patients, usually in mild or mild forms of the disease.

The described typical symptom complex of the initial (pre-icteric) period of hepatitis A is in full accordance with the features of the pathogenesis of the disease. The generalization of the infection (viremia) occurring during this period is reflected in the manifestations of infectious toxicosis in the first days of the disease with a clinical picture that is uncharacteristic in terms of specificity, after which, already on the 3rd-4th day of the disease, along with the subsidence of the infectious-toxic syndrome, symptoms of hepatitis A are revealed and gradually increase, indicating an ever-increasing disruption of the functional state of the liver.

Symptoms of intoxication of the initial period are in a correlative dependence on the concentration of the virus in the blood. The highest concentration of the viral antigen is detected in the first days of the initial period, when the symptoms of intoxication are most pronounced. At the end of the prodromal period, the concentration of the virus in the blood begins to decrease, and already from 3-5 days from the onset of jaundice, the viral antigen in the blood, as a rule, is not detected.

The manifestations of the initial (pre-icteric) period of hepatitis A are polymorphic, but this cannot serve as a basis for distinguishing individual clinical syndromes (astenovegetative, dyspeptic, catarrhal, etc.), as many authors do. In children, such a distinction between syndromes seems inappropriate, since syndromes are observed mostly in combination, and it is difficult to distinguish the leading significance of any of them.

Despite the heterogeneity of clinical manifestations and the absence of pathognomonic symptoms of hepatitis A in the pre-icteric period, hepatitis A can be suspected in this period based on the characteristic combination of intoxication symptoms with signs of incipient liver damage (enlargement, compaction and soreness). The diagnosis is significantly simplified by the presence of dark urine and discolored feces, an epidemic situation and can be supported by laboratory tests. The most important of them in this period of the disease is hyperenzymemia. The activity of almost all liver cell enzymes (ALT, AST, F-1-FA, sorbitol dehydrogenase, glutamate dehydrogenase, urocaninase, etc.) is sharply increased in the first days of the disease in all patients. The thymol test and beta-lyloproteins also increase.

Determination of bilirubin in the blood serum in this period of the disease has less diagnostic value, compared to enzymatic tests and sedimentation tests. The total amount of bilirubin at the beginning of the disease is not yet increased, but it is still often possible to detect an increased content of its bound fraction. From the first days of the disease, the amount of urobilin in the urine increases, and at the end of the pre-icteric period, bile pigments are detected with great regularity,

Changes in peripheral blood are not typical. Red blood is not changed, ESR is not increased, sometimes a quickly passing slight leukocytosis is noted.

The duration of the prodromal period, according to different authors, varies within quite significant limits: from several days to 2 or even 3 weeks. In children, it generally does not exceed 5-8 days, only in 13% of patients the pre-icteric period is from 8 to 12 days.

Most authors believe that the duration of the prodromal period depends on the severity of the disease. In adults, the disease is milder the shorter the prodromal period. According to our data, which are consistent with the data of most pediatricians, the severity of viral hepatitis is greater, the shorter the pre-icteric period. In mild forms of hepatitis A, jaundice usually appears on the 4th-7th day, and in moderate forms - on the 3rd-5th. At the same time, in mild forms, the disease begins immediately with the appearance of jaundice 2 times more often than in moderate forms. This is apparently explained by the fact that in mild forms, the symptoms of intoxication in the pre-icteric period are so weakly expressed that they can remain unnoticed.

Symptoms of hepatitis A in the icteric period

The transition to the peak period (icteric period) usually occurs with the onset of a clear improvement in the general condition and a decrease in complaints. With the appearance of jaundice, the general condition of 42% of patients with hepatitis A can be assessed as satisfactory, and in the rest - as moderately severe for another 2-3 days of the icteric period. In the following days, these patients also show practically no symptoms of intoxication or are weakly expressed, and the general condition can be assessed as satisfactory.

At first, yellowness of the sclera, hard and soft palate appears, then - the skin of the face, body, later - the extremities. Jaundice increases quickly, within 1-2 days, often the patient turns yellow as if "overnight".

Jaundice in hepatitis A can be mild or moderate in intensity. Having reached its peak, jaundice in hepatitis A begins to decrease in 2-3 days and disappears in 7-10 days. In some cases, it can linger for 2-3 weeks. Jaundice lasts the longest in the folds of the skin, on the auricles, the mucous membrane of the soft palate, especially under the tongue and on the sclera - in the form of "marginal icterus with margins". Itching of the skin is not typical for hepatitis A, but in some cases at the height of jaundice it is possible, especially in children of the prepubertal or pubertal periods, as well as in adults.

Skin rashes are not typical for hepatitis A; only a few patients experience urticarial rash, which can always be associated with a food allergy.

With the appearance of jaundice, the liver size increases further, its edge becomes denser, rounded (less often sharp), painful to palpation. The increase in liver size corresponds mainly to the severity of hepatitis: in a mild form of the disease, the liver usually protrudes from under the edge of the costal arch by 2-3 cm, and in a moderate form - by 3-5 cm.

The increase in liver size is mostly uniform, but often one lobe, usually the left, is predominantly affected.

An enlarged spleen in hepatitis A is observed relatively rarely - no more than in 15-20% of patients, but still this symptom of hepatitis A can be attributed to typical or even pathognomonic signs of the disease. Usually the spleen protrudes from under the edge of the costal arch by no more than 1-1.5 cm, its edge is rounded, moderately compacted, painless on palpation. An enlarged spleen is usually noted at the height of the acute period: with the disappearance of jaundice, the spleen is palpated only in isolated patients. Most authors do not recognize a definite connection between an enlarged spleen and the severity of the disease, as well as the intensity of jaundice.

Changes in other organs with hepatitis A are weakly expressed. It is possible to note only moderate bradycardia, some decrease in arterial pressure, weakening of heart tones, impurity of the first tone or a slight systolic murmur at the apex, a slight accentuation of the second tone on the left ventricular artery, short-term extrasystoles.

Cardiovascular changes in hepatitis A never play a significant role in the course of the disease. Electrocardiographic changes, expressed mainly in flattening and lowering of the T wave, slight acceleration of the QRS complex, sometimes some decrease in the ST interval, should be interpreted as a result of extracardiac influences, i.e. as an "infectious heart", and not as an indicator of myocardial damage.

Changes in the nervous system in the clinical picture of hepatitis A are not of significant importance. However, at the onset of the disease, some general depression of the central nervous system can be detected, expressed in mood changes, decreased activity, lethargy, and dynamism, sleep disturbances and other manifestations.

In typical cases of hepatitis A, urine is intensely dark-colored (especially foam), and its quantity is reduced. At the height of clinical manifestations, traces of protein, single erythrocytes, hyaline and granular cylinders are often found in urine.

The excretion of bilirubin in the urine is one of the characteristic symptoms of all hepatitis. Clinically, this is expressed by the appearance of dark urine. In hepatitis A, the intensity of bilirubin excretion in the urine strictly correlates with the content of conjugated (direct) bilirubin in the blood - the higher the level of direct bilirubin in the blood, the darker the color of the urine. In this period of the disease, functional liver tests are changed to the maximum. The bilirubin content in the blood serum is increased, mainly due to the conjugated fraction, the activity of liver-cell enzymes is always increased, changes in other types of metabolism increase.

Hematological changes in hepatitis A are ambiguous; they depend on the stage of the disease, the age of the patient and the severity of the pathological process.

At the height of the disease, some thickening of the blood is observed with a simultaneous increase in the amount of intracellular fluid. The hematocrit index increases. The volume of the erythrocyte increases with an almost unchanged average hemoglobin content. The number of erythrocytes does not change significantly. The percentage of reticulocytes at the height of the disease is often increased. In the puncture of the sternum, an increase in the number of erythroblastic elements, bone marrow erythropenia, mild eosinophilia, maturation (within small limits) of granuloblastic elements are found. Some increase in the number of differentiated cellular elements and a pronounced plasma cell reaction are also noted. All these changes can be explained by the state of irritation of the erythropoiesis apparatus of the bone marrow by the causative virus.

ESR in hepatitis A is normal or slightly slow. Its increase is observed when a bacterial infection is added. In white blood, normocytosis or moderate leukopenia is most common, with relative and absolute neutropenia. monocytosis and lymphocytosis. Only in some cases - mild leukocytosis. In some cases, an increase in plasma cells is noted.

For the initial (pre-icteric) period, a slight leukocytosis with a shift to the left is typical; with the appearance of jaundice, the number of leukocytes is normal or below normal; during the convalescence period, the number of leukocytes is normal.

The phase of reverse development occurs on the 7th-14th day from the onset of the disease and is characterized by the complete disappearance of intoxication symptoms, improved appetite, reduction and disappearance of jaundice, a significant increase in diuresis (polyuria), bile pigments are not detected in the urine and urobilin bodies appear, feces are colored.

In the normal course of the disease, the decline in clinical manifestations continues for 7-10 days. From this point on, patients feel quite healthy, but in addition to an increase in the size of the liver and sometimes the spleen, their functional liver tests remain pathologically altered.

The recovery or convalescent (pre-icteric) period is characterized by normalization of liver size and restoration of its functional state. In some cases, patients may still complain of rapid fatigue after physical exertion, abdominal pain, enlarged liver, dysproteinemia, episodic or constant increase in the activity of hepatic cellular enzymes. These symptoms of hepatitis A are observed in isolation or in various combinations. The duration of the convalescent period is about 2-3 months.

The course of hepatitis A

The course of hepatitis A can be acute and protracted in duration, and smooth in nature, without exacerbations, with exacerbations, as well as with complications from the biliary tract and with the layering of intercurrent diseases.

The distinction between acute and protracted course is based on the time factor. In acute course, complete restoration of liver structure and function occurs in 2-3 months, while in protracted course - in 5-6 months from the onset of the disease.

Acute course

Acute course is observed in 90-95% of patients with verified hepatitis A. Within the acute course, there may be a very rapid disappearance of clinical symptoms of hepatitis A, and by the end of the 2-3rd week of the disease, complete clinical recovery occurs with normalization of the functional state of the liver, but there may also be a slower reverse dynamics of clinical manifestations with a slow dark recovery of liver functions. In these patients, the total duration of the disease fits into the time frame of acute hepatitis (2-3 months), but for 6-8 weeks after the disappearance of jaundice, certain complaints may remain (loss of appetite, discomfort in the liver, etc.), as well as an increase, hardening or soreness of the liver, rarely - an increase in the size of the spleen, incomplete normalization of liver functions (according to the results of functional tests), etc.

Among the 1158 children we examined who had had hepatitis A, by the time of discharge from the hospital (25-30th day of illness), 2/3 had no clinical symptoms of hepatitis A at all, and most liver function tests had returned to normal. Intoxication symptoms had disappeared in 73% of children by the 10th day of illness. Yellowness of the skin had disappeared by the 15th day of illness in 70% of children, while in the remaining 30% it persisted as slight icterus of the sclera for up to 25 days. Complete normalization of pigment metabolism indices had occurred by the 20th day of illness in 2/3 of children, and by the 25-30th day of illness in the rest. The activity of liver cell enzymes had reached normal values by this time in 54% of patients; In 41% of children, the liver size had normalized by this period, in the remaining 59%, the liver edge protruded from under the costal arch (by no more than 2-3 cm), but in most of them this increase could be associated with age-related features. After 2 months from the onset of the disease, only 14.2% of children who had had hepatitis A had minor hyperenzymemia (ALT activity exceeded normal values by no more than 2-3 times) in combination with a slight increase in liver size (the liver edge protruded from under the costal arch by 1-2 cm), an increase in the thymol test indicator and dysproteinemia. We assessed the pathological process in these cases as protracted convalescence. The further course of the disease in most of these patients was also benign.

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Protracted course

According to modern concepts, protracted hepatitis should be understood as a pathological process characterized by persistent clinical, biochemical and morphological signs of active hepatitis, lasting from 3 to 6-9 months. In hepatitis A, protracted hepatitis is relatively rare. S. N. Sorinsoy observed a protracted course of hepatitis A in 2.7% of patients, I. V. Shakhgildyan - in 5.1, P. A. Daminov - in 10%. The relatively wide range of fluctuations in the frequency of protracted hepatitis A can be explained not only by the different composition of patients, but primarily by the different approaches to diagnosis. Protracted hepatitis is usually considered to include all cases of the disease lasting from 3 to 9 months. In hepatitis A, protracted hepatitis should be diagnosed if the duration of the disease is more than 2 months.

In the observed patients with protracted hepatitis A, the initial manifestations of the disease differed little from those in acute hepatitis. The disease, as a rule, began acutely, with a rise in body temperature to 38-39 ° C and the appearance of intoxication symptoms. The duration of the pre-icteric period averaged 5 + 2 days. With the appearance of jaundice, the symptoms of intoxication usually weakened. Jaundice reached its maximum severity on the 2nd-3rd day of the icteric period. In most cases, the symptoms of intoxication and jaundice disappeared within the time frame corresponding to the acute course of the disease. Violation of the cyclicity was detected only in the period of early convalescence. At the same time, the size of the liver remained enlarged for a long time, rarely - the spleen. In the blood serum, the activity of liver-cell enzymes did not show a tendency to normalize, and the thymol test values remained high. In a quarter of patients with clear initial positive dynamics of clinical and biochemical parameters during the convalescence period, the activity of ALT and F-1-FA increased again and the results of the thymol test increased, while only in isolated cases did minor (the amount of bilirubin was not higher than 35 μmol/l) and short-term jaundice appear.

It is important to emphasize that protracted hepatitis A always ends in recovery.

Morphological data obtained during a liver puncture biopsy 4-6 months after the onset of the disease indicated a continuation of the acute process in the absence of signs of chronic hepatitis.

The presented factual data show that the recovery process in case of protracted hepatitis A can be significantly delayed and last for more than 6 months. However, this does not give grounds to consider such forms as chronic hepatitis. The origin of protracted hepatitis A is based on the peculiarities of the immunological response. The indices of cellular immunity in such patients throughout the acute period are characterized by a slight decrease in the number of T-lymphocytes and an almost complete absence of shifts in the immunoregulatory subpopulations. At the same time, the ratio of T-helpers/T-suppressors does not deviate from normal values. The absence of redistribution of immunoregulatory subpopulations, presumably, does not contribute to globulin production. In patients with protracted hepatitis A, the number of B-lymphocytes and the concentration of serum IgG and IgM at the height of the acute period are usually within normal values, and the level of specific anti-HAV class IgM, although it increases, is insignificant. Only at the end of the 2nd month from the onset of the disease is there a slight decrease in the number of T-suppressors, which ultimately leads to an increase in the number of B-lymphocytes, an increase in the concentration of serum immunoglobulins by 1.5-2 times and an increase in the level of specific anti-HAV class IgM. Such immunological shifts led to a delayed, but still complete elimination of the virus and recovery.

Thus, in terms of the nature of the immunological response, protracted hepatitis A is similar to acute hepatitis, with the only difference being that it is characterized by slow specific immunogenesis and the formation of an extended cycle of the infectious process.

Current with exacerbation

An exacerbation is an increase in the clinical signs of hepatitis and a deterioration in the indices of functional liver tests against the background of a persistent pathological process in the liver. Exacerbations should be distinguished from relapses - the repeated occurrence (after a period of absence of visible manifestations of the disease) of the main syndrome of the disease in the form of an increase in the size of the liver, often the spleen, the appearance of jaundice, an increase in body temperature, etc. Relapses can also occur in the form of anicteric variant. Both exacerbations and relapses are always accompanied by an increase in the activity of hepatocellular enzymes. Corresponding changes in sedimentary protein tests and other laboratory tests are detected. In some cases, only a deviation from the norm in liver tests is noted without any clinical manifestations of the disease. These are the so-called biochemical exacerbations.

The causes of exacerbations and relapses are currently not precisely established. Considering that relapses occur in most cases 2-4 months after the onset of hepatitis A, superinfection with viruses of another type of hepatitis can be assumed. According to the literature, in half of the cases during a relapse, transient HBs antigenemia is detected, which indicates superimposed hepatitis B. It has been shown that with superimposition of hepatitis B, the course of hepatitis A can be undulating due to enzymatic exacerbations, or relapses occur, proceeding with a typical clinical picture of hepatitis B. Studies conducted in our clinic confirm the leading role of superinfection in the occurrence of relapses in hepatitis A. In almost all patients with the so-called relapse of hepatitis A, we documented superinfection with the HB virus or could not exclude the superimposition of viral hepatitis "neither A nor B".

However, if the issue of the genesis of hepatitis A relapses is resolved by most researchers unequivocally - superposition of another type of hepatitis, then it is not always easy to understand the cause of exacerbations. Quite often, exacerbations of hepatitis A occur in patients with the so-called protracted convalescence, that is, against the background of still-preserved activity of liver-cell enzymes and deviations from the norm of other liver tests. The growth of the activity of the pathological process in the liver in such cases occurs without apparent reasons and, as a rule, against the background of circulation in the blood of specific anti-HAV class IgM. Of course, one can assume that in these cases there is infection with another antigenic variant of the hepatitis A virus, but there are still more grounds to believe that the main cause of exacerbation is the activation of the virus in a patient with functional insufficiency of the immune system and a delay in a full-fledged immunological response, which can result in a low level of specific antibodies of genesis and a repeated breakthrough of the virus into free circulation. In a number of cases, in the period preceding the exacerbation, we observed a decrease in the titer of anti-HAV class IgA in the blood serum.

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Course with damage to the bile ducts

In hepatitis A, biliary tract damage is usually accompanied by dyskinetic phenomena, which can be diagnosed at any stage of the disease. The predominant type of dyskinesia is hypertonic, characterized by hypertension of the depressor muscle, increased tone of the cystic duct and gallbladder. These changes are observed in any form of hepatitis A, but are more pronounced in the moderate form, especially in patients with cholestatic syndrome.

In most patients with foxes, kinetic phenomena in the biliary tract pass without any treatment as the symptoms of viral liver damage are eliminated, which allows their occurrence in the acute period of the disease to be associated directly with HAV infection. Biliary tract damage in the acute period of hepatitis A does not significantly affect the nature of the course of the pathological process in the liver. The total duration of the disease in most cases falls within the framework of acute hepatitis. Only in rare cases is biliary tract damage accompanied by cholestatic syndrome. Biliary tract damage is often detected in the recovery period. In this case, patients complain of periodic abdominal pain, nausea, and sometimes vomiting. They often have belching on an empty stomach. An objective examination can detect liver pain, mainly in the projection of the gallbladder. In some cases, positive "bladder" symptoms of hepatitis A and hepatomegaly without distinct subjective complaints are noted.

Course with overlapping intercurrent diseases

It is generally accepted that the combination of two infectious diseases always affects their clinical course. Many also consider intercurrent diseases as one of the possible causes of exacerbations, relapses and protracted course of hepatitis A.

The literature expresses an opinion about the aggravating effect on the course of the disease of such intercurrent infections as dysentery, pneumonia, typhoid fever, acute respiratory viral infections, measles, whooping cough, as well as helminthic invasion, gastroduodenitis, ulcerative colitis and many others.

It should be noted, however, that most of the literature data on the problem of mixed hepatitis is unconvincing, since the observations were carried out on verified hepatitis A and, therefore, did not exclude hepatitis B, C and “neither A nor B” in this group of patients.

Among the 987 patients with verified hepatitis A that we observed, in 33% of cases the disease occurred in combination with other infections, including 23% with acute respiratory viral infections and 4% with urinary tract infections.

There is no significant influence of intercurrent diseases on the severity of clinical manifestations, the degree of functional disorders, as well as the nature of the course, immediate and remote outcomes of hepatitis A. Only in individual patients with superimposed intercurrent disease were enlarged liver size, increased activity of hepatic-pulmonary enzymes, increased thymol test values, and even a slower rate of functional recovery of the liver observed again. However, even in these patients it was not possible to associate the noted changes exclusively with the superimposed infection. Obviously, the issue of the mutual influence of hepatitis A and concomitant diseases cannot be considered completely resolved; in our opinion, there are no sufficient grounds to exaggerate the significance of intercurrent diseases for the severity, nature of the course, and outcomes of hepatitis A.

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Classification of Hepatitis A

Hepatitis A is classified by type, severity and course.

Severity indicators:

• clinical - increased body temperature, vomiting, decreased appetite, hemorrhagic manifestations, intense jaundice, enlarged liver;
• laboratory - bilirubin content, prothrombin, sublimate titer, etc.

Type	Form	Flow
		By duration	By nature
Typical	Light Medium Heavy	Acute Protracted	Without exacerbations With exacerbations With complications from the biliary tract With intercurrent diseases
Atypical	Anicteric Erased Subclinical

Typical forms include all cases accompanied by the appearance of yellowing of the skin and visible mucous membranes, atypical forms include non-icteric, erased and subclinical. Typical hepatitis A can be mild, moderate or severe. Atypical cases are usually mild.

As with other infectious diseases, the severity of hepatitis A can only be assessed at the height of the disease, when all the symptoms of hepatitis A have reached their maximum development, while it is necessary to take into account the severity of the pre-icteric period.

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Clinical forms of hepatitis A

Symptoms of general intoxication (increased body temperature, vomiting, adynamia, decreased appetite) in the initial, pre-icteric period are more pronounced, the more severe the form of the disease. A short pre-icteric period is typical for more severe forms. Differences in intoxication depending on the severity of the disease are especially clearly revealed in the icteric period. In mild and moderate forms of the disease, with the appearance of jaundice, the symptoms of intoxication significantly weaken or even disappear completely. In severe forms, with the appearance of jaundice, the condition of patients, on the contrary, worsens due to the appearance of "metabolic" or secondary toxicosis. Patients complain of headache, dizziness, general weakness, loss of appetite.

Objective criteria for the severity of viral hepatitis in patients include the degree of enlargement of the liver and the intensity of jaundice.

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Moderate hepatitis A

Occurs in 30% of patients. Characterized by moderate symptoms of intoxication. In the pre-icteric period, the body temperature rises to 38-39 °C for 2-3 days. Characterized by lethargy, mood swings, dyspeptic symptoms (nausea, vomiting), abdominal pain, sometimes bowel disorder. The duration of the pre-icteric period is on average 3.3±1.4 days, i.e. it is shorter than in mild forms of the disease. With the appearance of jaundice, the symptoms of intoxication, although weakening, persist; lethargy and loss of appetite - in all, nausea, sometimes vomiting - in a third, subfebrile body temperature - in half of the patients. Jaundice from moderate to significant, in isolated cases itching of the skin is possible. The liver is painful, its edge is dense, protrudes from under the costal arch by 2-5 cm. The spleen is enlarged in 6-10% of patients, palpated at the edge of the costal arch. Bradycardia is often noted, and often - hypotension. The amount of urine is reduced.

In the blood serum, the level of total bilirubin is from 85 to 150 μmol/l, rarely up to 200 μmol/l, including free (indirect) up to 50 μmol/l. A decrease in the prothrombin index (up to 70%), sublimate titer (up to 1.7 U) is possible. The activity of organ-specific enzymes exceeds normal values by 15-25 times.

The course of the disease is usually cyclical and benign. Symptoms of intoxication usually persist until the 10th-14th day of the disease, jaundice - 2-3 weeks. Complete restoration of the liver structure and function occurs on the 40th-60th day of the disease. A protracted course is observed in only 3% of patients.

Severe form of hepatitis A

It is extremely rare in hepatitis A, occurring in no more than 5% of patients. It seems that severe forms of hepatitis A are much more common in waterborne infections.

The distinctive signs of a severe form are intoxication and pronounced biochemical changes in the blood serum. The disease always begins acutely with a rise in body temperature to 39-40 °C. From the first days, weakness, anorexia, nausea, repeated vomiting, abdominal pain are characteristic, dizziness and upset stomach are possible. The pre-icteric period is often short - 2-3 days. With the appearance of jaundice, the condition of patients remains severe. Patients complain of general weakness, headache, dizziness, complete lack of appetite. Jaundice increases quickly, within 24 hours, usually bright, but there is no itching. Hemorrhagic rashes are possible on the skin, they usually appear on the neck or shoulders after the application of a tourniquet due to intravenous manipulations. Heart sounds are muffled, the pulse is rapid, blood pressure tends to decrease. The liver is sharply enlarged, its palpation is painful, the spleen is enlarged.

The total bilirubin content in the blood serum is more than 170 μmol/l. The level of conjugated bilirubin is predominantly increased, but 1/3 of the total bilirubin is the free fraction. The prothrombin index decreases to 40%, the sublimate titer - to 1.4 BD, the activity of organ-specific liver-cell enzymes is sharply increased, especially in the pre-icteric period and in the first days of jaundice. The disease proceeds smoothly. A protracted course is almost never encountered.

Anicteric form of hepatitis A

The distinctive feature of this form of the disease is the complete absence of hysteria of the skin and sclera throughout the disease. During targeted examination of groups in epidemic foci of hepatitis A, anicteric forms are diagnosed 3-5 times more often than icteric ones.

The clinical manifestations of the anicteric form are practically no different from those of mild typical forms.

Anicteric forms of hepatitis A are characterized by a combination of dyspeptic and asthenovegetative symptoms with an increase in the size of the liver, as well as a change in the color of urine due to an increase in the concentration of urobilin and bile pigments. Increased activity of hepatic cell enzymes (ALT, AST, F-1-FA, etc.) is always detected in the blood serum, the thymol test values are significantly increased, the content of conjugated bilirubin often increases, but the level of total bilirubin does not exceed 35 μmol / l. The prothrombin index and sublimate titer are always within normal values. Clinical symptoms of hepatitis A, with the exception of an increase in the size of the liver, as well as violations of biochemical parameters, in anicteric forms last for a short time. The general condition of the patient is practically not disturbed, and therefore, with insufficiently careful observation, the patient can endure the disease on his feet, remaining in the team.

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Erased form

The latent form includes cases of viral hepatitis with weakly expressed main symptoms of the disease. A distinctive feature of the latent form is barely noticeable yellowness of the skin, visible mucous membranes and sclera, which disappears after 2-3 days. In the latent form, the symptoms of hepatitis A of the initial (prodromal) period are expressed insignificantly or are absent. A short-term (1-2 days) increase in body temperature, lethargy, weakness, deterioration of appetite are possible: an increase in the size of the liver is insignificant. Dark urine and discolored feces are observed with great constancy, but for a short time. Moderately increased activity of liver-cell enzymes is detected in the blood. The content of total bilirubin is slightly increased due to the conjugated (direct) fraction. The thymol test indicators are increased by 1.5-2 times. In general, the clinical and biochemical manifestations of the latent form can be characterized as a light, rudimentary variant of the mild typical form, which has an abortive course. Its significance, as with the anicteric form, lies in the difficulty of recognition, with the ensuing epidemiological consequences.

Subclinical (inapparent) form

In this form, unlike anicteric and erased, there are no clinical manifestations at all. The diagnosis is made only by laboratory examination of those in contact with patients with viral hepatitis. Of the biochemical tests, the most important for the diagnosis of such forms are the indices of enzymatic activity, and above all, an increase in the activity of ALT and F-1-FA in the blood serum; less often, the activity of AST increases and a positive thymol test is detected. In all patients with the subclinical form of hepatitis A, specific antibodies are found in the blood - anti-HAV class IgM, which is of decisive importance for diagnosis. It is widely believed that in the focus of hepatitis A, most patients become infected and suffer mainly from the inapparent form of the disease. In the foci of hepatitis A, for one disease diagnosed clinically and with the help of biochemical tests, an average of 5-10 patients with the presence of the hepatitis A virus in feces are detected. It has been shown that if contacts in hepatitis A foci are examined using only biochemical tests, the disease is detected in an average of 15%, whereas when virological methods are used, it is detected in 56 and even 83% of contacts.

The high prevalence of subclinical forms of hepatitis A is evidenced by the fact that among patients with anti-HAV class IgM, only 10-15% suffer from the icteric form of the disease. The significance of inapparent subclinical forms of hepatitis A is that, remaining unrecognized, they, like anicteric forms, serve as an invisible link, constantly supporting the chain of the epidemic process.

Viral hepatitis A with cholestatic syndrome

In this variant of viral hepatitis, the symptoms of mechanical jaundice come to the forefront in the clinical picture. There is reason to believe that this form of the disease has no clinical independence. Cholestasis syndrome can occur both in mild and in more severe forms of the disease. Its development is based on bile retention at the level of the intrahepatic bile ducts. It is suggested that bile retention occurs due to damage to cholangioli directly by the virus itself. Many authors point to the involvement of intrahepatic bile ducts in the pathological process in viral hepatitis. In this case, swelling, granularity of the cytoplasm of the epithelium, damage to the plasma membranes of the bile capillaries, karyolysis of the nuclei of the ductular epithelium cells are observed. Inflammatory changes in the intrahepatic bile ducts, their increased permeability, diapedesis of bile, an increase in its viscosity lead to the formation of blood clots, large bilirubin crystals; difficulties arise in the movement of bile through the bile capillaries and cholangioles. To a certain extent, intracanalicular bile retention is associated with pericholangiolytic and periportal infiltration, which occurs as a consequence of hyperergic disorders. It is also impossible to exclude the participation of the hepatocytes themselves in this process, namely, an increase in the permeability of cell membranes with the development of direct communications between the bile capillaries and the Disse space, which presumably entails the appearance of excess protein in the bile, its thickening and the formation of thrombi.

In relation to the cholestatic form of viral hepatitis, the point of view of the authors of the past is not without foundation. According to it, the main cause of cholestasis is a mechanical obstruction that occurs at the level of the bile ducts, gall bladder and even the muscle-constrictor of the common bile duct.

In the literature, these forms of the disease are described under different names: “acute icteric form with cholestatic syndrome”, “cholestatic, or cholangiolytic, hepatitis”, “hepatitis with intrahepatic cholecystitis”, “cholangiolytic hepatitis”, “viral hepatitis with prolonged bile retention”, etc.

Literature data on the frequency of the cholestatic form of viral hepatitis are quite contradictory: from 2.5 to 10%.

The leading clinical symptom of hepatitis A with cholestatic syndrome is more or less pronounced congestive jaundice for a long time (up to 30-40 days or more) and itching of the skin. Often the jaundice has a greenish or saffron tint, but sometimes the jaundice of the skin can be weakly expressed, and the clinical picture is dominated by itching of the skin. There are no symptoms of intoxication in the cholestatic form or they are weakly expressed. The liver size increases slightly. Urine is usually dark, and the cap is discolored. The bilirubin content in the blood serum is usually high, exclusively due to the conjugated fraction. The activity of liver cell enzymes increases moderately from the first days, and then, despite the high bilirubin content in the blood serum, decreases to almost normal values. Characteristic of the cholestatic form can be considered a high content of beta-lipoproteins, total cholesterol, as well as a significant increase in the activity of alkaline phosphatase and leucine aminopeptidase in the blood serum. The indicators of other functional tests (sublimate test, level of coagulation factors, thymol test, etc.) change insignificantly or remain within normal values.

The course of hepatitis A with cholestatic syndrome, although long, is always favorable, and complete restoration of the functional state of the liver occurs. Chronic hepatitis does not develop.

Hepatitis A Outcomes

The outcomes of hepatitis A are recovery with complete restoration of the structure and function of the liver, recovery with an anatomical defect (residual fibrosis) or the formation of various complications from the biliary tract and gastroduodenal zone.

Recovery with complete restoration of liver structure and function

According to one of the clinics, out of 1158 children who had hepatitis A, by the time of discharge from the hospital (25-30th day of illness) clinical recovery and normalization of biochemical tests were noted in 50% of cases, after 2 months - in 67.6%, after 3 months - in 76%, after 6 months - in 88.4%; in the remaining 11.6% of children, various consequences of hepatitis A were detected 6 months after the onset of the disease, including 4.4% - enlargement and hardening of the liver with full preservation of its functions, 7.2% - abdominal pain due to biliary dyskinesia (3%), cholecystitis or cholangitis 0.5%), gastroduodenitis (2.5%), pancreatopathy (0.2%). In no case was the formation of chronic hepatitis observed.

Recovery with anatomical defect, posthepatitis hepatomegaly (residual fibrosis).

Long-term or lifelong persistent enlargement of the liver after hepatitis A in the complete absence of clinical symptoms and laboratory changes is possible. The morphological basis of hepatomegaly is residual liver fibrosis. In this case, dystrophic changes in hepatocytes are completely absent, but proliferation of Kupffer cells and coarsening of the stroma are possible. It should be noted, however, that not every enlargement of the liver after acute hepatitis can be regarded as residual fibrosis. An increase in the size and compaction of the liver 1 month after discharge from the hospital is noted in 32.4% of children, 3 months - in 24, and 6 months - in 11.6% of patients. In all these patients, the liver protruded from under the edge of the costal arch by 1.5-2.5 cm and was painless, and biochemical tests indicated complete restoration of its functional activity. According to formal signs, such an increase in liver size could be interpreted as residual liver fibrosis as a result of hepatitis A. However, upon careful study of the anamnesis and as a result of targeted examination (ultrasound, immunological tests, etc.), in most of these patients, an increase in liver size was assessed as a constitutional feature or as a result of other diseases suffered earlier. Only in 4.5% of patients was residual fibrosis documented as a result of hepatitis A.

Bile duct disease

It is more correct to interpret the biliary tract lesion not as an outcome, but as a complication of hepatitis A, which occurs as a result of combined lesion of the biliary tract by the virus and secondary microbial flora. By its nature, this is a diekinetic or inflammatory process. It is often combined with lesion of other parts of the gastrointestinal tract, gastroduodenitis, pancreatitis, enterocolitis.

Clinically, bile duct damage manifests itself with complaints of various nature (pain in the right hypochondrium or epigastrium, often periodic or paroxysmal, associated with food intake, sometimes a feeling of heaviness or pressure in the right hypochondrium, nausea, vomiting). As a rule, abdominal pain appears 2-3 months after hepatitis A.

Among the 1158 patients with hepatitis A observed, abdominal pain was noted in 84 cases 6 months after the onset of the disease, which is 7.2%. All these patients, along with moderate hepatomegaly, complained of abdominal pain, nausea, sometimes vomiting, belching on an empty stomach or associated with food intake. Palpation revealed pain in the epigastric region. Some patients had positive "bladder" symptoms and hepatomegaly without distinct subjective complaints. A comprehensive clinical and laboratory examination allowed us to exclude the development of chronic hepatitis in all these patients. To clarify the diagnosis, they were examined in depth in a gastroenterological center using modern research methods (fibrogastraduodenoscopy, colonoscopy, irrigosconia, fractional study of gastric juice, duodenal intubation, etc.).

Anamnestic data analysis revealed that half of the patients had complaints of abdominal pain and dyspeptic disorders before they contracted hepatitis A. Some patients were treated in somatic hospitals for chronic gastroduodenitis, biliary dyskinesia, chronic colitis, etc. The duration of these diseases before hepatitis A was 1-7 years. In the early stages of convalescence (2-4 weeks after discharge from the hepatitis hospital), all of these patients again developed abdominal pain and dyspeptic symptoms of hepatitis A. During examination, most were diagnosed with exacerbation of chronic gastroduodenitis. FGDS revealed changes in the mucous membrane of the stomach and duodenum in 82% of cases. In some cases, in the absence of endoscopic signs of damage, functional disorders of the acid- and secretion-forming function of the stomach were detected. Combined pathology of the gastroduodenal system, intestines and biliary tract was often detected.

A retrospective analysis of anamnestic data showed that the majority of these patients (62%) had a burdened heredity for gastroenterological pathology, manifested by food or polyvalent allergies, bronchial asthma, neurodermatitis, etc.

38% of patients had no complaints of abdominal pain or any dyspeptic disorders before contracting hepatitis A. They developed pain 2-3 months after the onset of hepatitis and were of varying nature, more often early after eating, less often late, or were constant. As a rule, pain arose in connection with physical exertion, and was paroxysmal or aching. Dyspeptic symptoms usually included nausea, less often vomiting, unstable stool, belching, heartburn, and constipation.

Clinical examination revealed pain on palpation in the epigastric and pyloroduodenal region, in the right hypochondrium and at the point of the gallbladder. All these patients had an increase in the liver size (the lower edge protruded from under the costal arch by 2-3 cm) and positive "bladder" symptoms of hepatitis A. Endoscopy revealed signs of damage to the mucous membrane of the stomach and duodenum in 76.7% of patients. In 63%, the pathology was combined (gastroduodenitis), and in 16.9% - isolated (gastritis or duodenitis). Only 17.8% of patients did not visually reveal changes in the mucous membrane of the stomach and duodenum. However, fractional examination of gastric juice revealed disturbances in the acid- and secretion-forming function of the stomach in some of them.

In the overwhelming majority of cases (85.7%), along with damage to the gastro-duodenal zone, dyskinetic disorders of the gallbladder were detected. In some patients, they were combined with an anomaly in the development of the gallbladder or with the phenomena of sluggish cholecystitis.

Thus, the so-called residual effects or remote consequences detected in hepatitis A convalescents in the form of long-term symptoms of general asthenia, vague abdominal pain, enlarged liver, dyspeptic complaints and other manifestations, which in practical work are usually interpreted as "posthepatitis syndrome", with a thorough targeted examination in most cases are deciphered as chronic gastroduodenal or hepatobiliary pathology that was detected or developed in connection with hepatitis A. That is why, if there are complaints of abdominal pain, heartburn; nausea or vomiting during the convalescence period of hepatitis A, it is necessary to conduct an in-depth examination of the patient in order to identify pathology from the gastroduodenal and biliary systems. Such convalescents should be observed by a gastroenterologist and receive appropriate therapy.

Posthepatitis hyperbilirubinemia

Posthepatitis hyperbilirubinemia can only be conditionally associated with viral hepatitis. According to modern concepts, this syndrome is caused by a hereditary defect in bilirubin metabolism, leading to a violation of the transformation of unconjugated bilirubin or a violation of the excretion of conjugated bilirubin and, as a consequence, to the accumulation of an indirect fraction of bilirubin (Gilbert's syndrome) or a direct fraction (Rotor, Dubin-Johnson syndromes, etc.) in the blood. This is a hereditary disease, and viral hepatitis in such cases is a provoking factor that reveals this pathology, as well as, for example, physical or emotional stress, acute respiratory viral infections, etc.

As a result of hepatitis A, Gilbert's syndrome develops in 1-5% of patients, usually within the first year after the acute period of the disease. It most often occurs in boys during puberty. The leading clinical symptom of hepatitis A is mild jaundice due to a moderate increase in unconjugated bilirubin in the blood (usually no more than 80 μmol/l) in the complete absence of signs characteristic of hemolytic jaundice and viral hepatitis. The same can be said about Rotor and Dubin-Johnson syndromes, with the only difference being that in these cases the blood contains an increased content of exclusively conjugated bilirubin.

Chronic hepatitis does not develop as a result of hepatitis A.

The benign nature of the process and the absence of chronicity in hepatitis A are also confirmed by the results of clinical and morphological studies by other authors.