Hepatitis A: symptoms

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

In a typical course of the disease, a cyclical sequence is clearly expressed with a successive change of four periods: incubation, pre-zhelthus, icteric and post-jaundice. Given that often without jaundiced forms, it is more correct to distinguish between the following periods of the disease, incubation, prodromal, or initial (pre-jaundiced), the period of height (full development of the disease) and the period of convalescence. The division into periods is to some extent schematic, since the line between them is not always distinct. In some cases, the initial (prodromal) period may be unexpressed, and the disease begins as if immediately with jaundice. The isolation of the incubation period is very important, since its precise delimitation allows for the 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 a time when the patient is most contagious.

The period of convalescence in accordance with its essence can also be called restorative, or reparation. This highlights its great clinical importance, since recovery in hepatitis A, although it is inevitable, yet still occurs in many stages and has several options.

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

[1], [2], [3]

The first signs of hepatitis A

The incubation period for hepatitis A is from 10 to 45 days. Apparently, only in rare cases it can shorten to 8 days or extend up to 50 days. In this period, no clinical manifestations of the disease are noted. However, the activity of hepatocellular enzymes (ALT, ACT, F-1-FA, etc.) increases in the blood and hepatitis A virus is found in free circulation. These data are of great practical importance, as they justify the expediency of carrying out serum studies in hepatitis A foci Blood levels of these enzymes are suspected for this disease.

The disease usually begins with an increase in body temperature to 38-39 C, less often to higher values, and the appearance of symptoms of intoxication (malaise, weakness, decreased appetite, nausea and vomiting). From the first days of illness, patients complain of weakness, headache, bitter taste and bad smell from the mouth, a feeling of heaviness or pain in the right upper quadrant, epigastrium or without specific localization. Pain usually dull or colicky in nature. They can be strong and create the impression of an attack of appendicitis, acute cholecystitis and even cholelithiasis. Characteristic for the prodromal period, a marked change in mood is expressed in irritability, increased nervousness, capriciousness, sleep disturbance. In two-thirds of patients in the pre-icteric period of the disease, repeated vomiting is noted, not associated with ingestion of food, water and medicines, rarely vomiting is repeated. Often occur rapidly transient dyspeptic disorders: flatulence, constipation, less often - diarrhea.

In rare cases (10-15%) in the initial period, catarrhal phenomena are noted in the form of congestion of the nose, hyperemia of the mucous membranes of the oropharynx, slight coughing. These patients, as a rule, have a high temperature reaction. Until recently, catarrhal phenomena in hepatitis A were attributed to the underlying disease, which led some authors to isolate the influenza-like variant of the pre-jaundice period. According to modern ideas, the hepatitis A virus does not affect the mucous membranes of the oropharynx and respiratory tract. The appearance of catarrhal phenomena in some patients in the initial period of hepatitis A should be regarded as manifestations of acute respiratory viral disease.

1-2, less often - 3 days after the onset of the disease, the body temperature is normalized, and the symptoms of intoxication somewhat weaken, but still general weakness, anorexia, nausea, vomiting, and usually pain in the abdomen.

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

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

The described typical symptom complex of the initial (pre-jaundiced) period of hepatitis A is in full compliance 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 of little specific character, after which, on the 3rd -4th day of the disease, along with the abatement of the infectious-toxic syndrome, Gradually the symptoms of hepatitis A increase, indicating an ever increasing violation of the functional state of the liver.

Symptoms of intoxication in the initial period are correlated with the concentration of the virus in the blood. The highest concentration of viral antigen is detected precisely 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 with 3-5 soups from the onset of jaundice, the virus antigen in the blood, as a rule, is not detected.

The manifestations of the initial (pre-hepatitis) period of hepatitis A are polymorphic, but this can not serve as a basis for isolating individual clinical syndromes (asthenovegetative, dyspeptic, catarrhal, etc.), as many authors do. In children, such a differentiation of syndromes seems inappropriate, since the syndromes are mostly observed in combination, and it is difficult to single out the leading significance of any of them.

Despite the heterogeneity of clinical manifestations and the absence of pathognomonic symptoms of hepatitis A of the pre-zhelto period, it is possible to suspect hepatitis A in this period on the basis of a characteristic combination of symptoms of intoxication with signs of beginning liver damage (enlargement, densification and soreness). The diagnosis is greatly simplified in the presence of dark color of urine and fecal decolorization, an epidemic situation and can be supported by laboratory tests. The most important among them in this period of the disease is hyperfermentemia. Activity of almost all hepatic-cell enzymes (ALT, ACT, F-1-FA, sorbitol dehydrogenase, glutamate dehydrogenase, urokaninase, etc.) is dramatically increased in the first days of the disease in all patients. The parameters of thymol test, beta-liloproteins are also increasing.

Determination of serum bilirubin in this period of the disease has less diagnostic significance, compared with enzymatic tests and sediment assays. The total amount of bilirubin at the onset of the disease has not yet been increased, but it is often possible to detect an increased content of its associated fraction. From the first days of the disease in the urine, the amount of urobilin increases, and at the end of the pre-jaundice period, bile pigments are found with great regularity,

Changes in peripheral blood are not characteristic. Red blood is not changed, ESR is not increased, sometimes there is a fast-passing small leukocytosis.

The duration of the prodromal period, according to different authors, fluctuates in fairly significant ranges: from a few days to 2 or even 3 weeks. In children it does not exceed 5-8 su for the most part, only 13% of patients have a pre-egg period ranging 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 proceeds the easier, the shorter the prodromal period. According to our data, with which the data of the majority of pediatricians are consistent, the severity of viral hepatitis is greater, the shorter the pre-jaundice period. In mild forms of hepatitis A jaundice usually appears on the 4th-7th day, and for the middle-heavy forms, 3-5. However, with mild forms 2 times more often than with the moderate, the disease begins immediately with the appearance of jaundice. This, apparently, is due to the fact that in mild forms the symptoms of intoxication in the pre-jaundiced period are so weak that they can go unnoticed.

Symptoms of hepatitis A in icteric period

The transition to the peak period (icteric period) usually occurs when there is a clear improvement in the general condition and a decrease in complaints. With the appearance of jaundice, the general condition in 42% of patients with hepatitis A can be regarded as satisfactory, and in others - as an average for another 2-3 days of icteric period. In the following days and in these patients the symptoms of intoxication are practically not determined or weakly expressed and the general condition can be assessed as satisfactory.

At the beginning there is icteric sclera, a hard and soft palate, then - skin of the face, trunk, later - of the limbs. Jaundice increases rapidly, within 1-2 days, often the patient turns yellow as if "overnight".

The intensity of jaundice with hepatitis A can be mild or moderate. Having reached the peak of development, jaundice with hepatitis A after 2-3 days begins to decrease and disappears after 7-10 days. In some cases, it can be delayed for 2-3 weeks. The 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 icterity with measures." Itching of the skin for hepatitis A is not typical, but in some cases at the height of jaundice it is possible, especially in pre-pubertal or pubertal children, as well as in adults.

Eruptions on the skin for hepatitis A are not typical only in single patients there is a urticaria rash, which can always be associated with food allergy.

With the appearance of jaundice there is a further increase in the size of the liver, its edge is densified, rounded (less often acute), painful when palpated. The increase in the size of the liver corresponds mainly to the severity of the hepatitis: with a mild form of the disease, the liver usually protrudes from the edge of the costal arch by 2-3 cm, and in the case of the moderate - by 3-5 cm.

The increase in the size of the liver is mostly uniform, but often the defeat of one lobe, usually the left one, predominates.

Increase in the size of the spleen in hepatitis A is relatively rare - no more than 15-20% of patients, but still this symptom of hepatitis A can be attributed to the typical or even pathognomonic signs of the disease. Usually the spleen protrudes from under the edge of the costal arch not more than 1-1.5 cm, its edge is rounded, moderately densified, painless on palpation. The increase in the size of the spleen, as a rule, is noted at the height of the acute period: with the disappearance of jaundice, the spleen is palpable only in single patients. Most authors do not recognize a definite connection between the increase in the spleen and the severity of the disease, as well as the intensity of jaundice.

Changes from other organs with hepatitis A are mild. You can only note a moderate bradycardia, a slight decrease in blood pressure, a weakening of the heart sounds, impurity of the I tone or a slight systolic noise at the top, a slight accent of the second tone for the years of the internal 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 the T wave, slight acceleration of the QRS complex, sometimes a slight decrease in the ST interval, should be interpreted as the result of extracardiac effects, that is, 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 significant. Nevertheless, at the onset of the disease, one can detect some common CNS depression, manifested in a change in mood, decreased activity, lethargy, and dynamism, and violation of sleep and other manifestations.

In hepatitis A, in typical cases urine intensively becomes dark (especially foam), its amount is reduced. At the height of clinical manifestations in the urine, traces of protein, single red blood cells, hyaline and granular cylinders are often found.

Urinary excretion of bilirubin is one of the characteristic symptoms of all hepatitis. Clinically, this is expressed by the appearance of a dark color of urine. In hepatitis A, the intensity of bilirubin release in the urine is strongly correlated 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 urine. In this period of the disease the functional tests of the liver are maximally changed. In the blood serum, the bilirubin content is increased, mainly due to the conjugated fraction, the activity of hepatic cell enzymes has always been increased, changes in each of their metabolic species are increasing.

Hematologic shifts 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, there is a certain thickening of the blood with a simultaneous increase in the amount of intracellular fluid. The indicator of hematocrit rises. Increases the volume of erythrocyte with an almost unchanged mean hemoglobin content. The number of red blood cells does not change significantly. The percentage of reticulocytes at the height of the disease is often elevated. In the puncture of the sternum, an increase in the number of erythroblastic elements, bone marrow erythropenia, mild eosinophilia, maturation (in small limits) of granuloblastic elements are found. There is also a slight increase in the number of differentiated cellular elements and a pronounced plasma cell reaction. All these changes can be explained by the state of irritation of the erythropoiesis apparatus of the bone marrow by the virus-causative agent of the disease.

ESR in hepatitis A is normal or slightly delayed. An increase in it is observed with the addition of a bacterial infection. In white blood, normocytosis or moderate leukopenia is more common, with relative and absolute neutropenia. Monocytosis and lymphocytosis. Only in some cases - mild leukocytosis. In a number of cases, an increase in plasma cells is noted.

For the initial (pre-jaundiced) period, a small leukocytosis with a shift to the left is typical, with the appearance of jaundice the number of white blood cells is normal or below normal, in the period of convalescence the number of white blood cells is normal.

The phase of reverse development occurs on the 7-14th day of the onset of the disease and is characterized by the complete disappearance of symptoms of intoxication, improvement in appetite, decrease and disappearance of jaundice, a significant increase in diuresis (polyuria), urine does not show bile pigments and urobilin bodies appear and stain stains.

In the normal course of the disease, the decline in clinical manifestations continues for 7-10 days. From this point on, patients feel completely healthy, but they, besides increasing the size of the liver, and sometimes the spleen, have pathologically altered functional liver tests.

Restorative, or reconvalescent (pre-zheltushny) period is characterized by normalization of liver size and restoration of its functional state. In a number of cases, patients can still complain of rapid fatigue after physical exertion, abdominal pain, increased liver size, the phenomenon of dyslroteinemia, episodic or permanent increase in the activity of hepatic cell enzymes. These symptoms of hepatitis A are observed in isolation or in various combinations. The duration of the convalescence period is about 2-3 months.

The course of hepatitis A

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

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

Acute current

Acute course is observed in 90-95% of patients with verified hepatitis A. Within the acute course there can be a very rapid disappearance of the clinical symptoms of hepatitis A, and by the end of the 2-3 weeks of the disease there is a complete clinical recovery with normalization of the functional state of the liver, but can there should be a slower reverse dynamics of clinical manifestations with slowed-down recovery of liver functions. In these patients, the total duration of the disease is within the time frame of acute hepatitis (2-3 months), but within 6 - 8 weeks after the disappearance of jaundice can remain those or other complaints (a violation of appetite, unpleasant sensations in the liver, etc.), as well as enlargement, compaction or pain of the liver, rarely - increase in the size of the spleen, incomplete normalization of liver functions (according to the results of functional tests) and etc.

Among the 1158 children who underwent hepatitis A, by the time of discharge from the hospital (25-30 days of illness), 2/3 had completely no clinical signs of hepatitis A and normalization of the majority of functional liver samples. At the same time, symptoms of intoxication in 73% of children disappeared by the 10th day of the disease. The jaundice of the skin in 70% of the children disappeared by the 15th day of the disease; in the remaining 30% it remained in the form of a small icteric sclera up to 25 days. Complete normalization of the parameters of pigmentation in 2/3 of the children came to the 20th, in the rest - to the 25-30th day of the disease. The activity of hepatic-cell enzymes reached normal values by this time in 54% of patients; in 41% of the children, the liver size was normalized in this period, in the remaining 59% the edge of the liver protruded from the rib arch (not more than 2-3 cm), but in most of them this increase could be related to the age features. At 2 months from the onset of the disease, only a mild hyperfermentemia was noted in 14.2% of children undergoing hepatitis A (the ALT activity exceeded normal values by no more than 2-3 times) in combination with a slight increase in liver size (the margin of the liver protruded from under costal arch for 1-2 cm), an increase in the thymol test and the phenomena of disproteinemia. The pathological process in these cases was regarded as a prolonged convalescence. The further course of the disease in most of these patients is also benign.

[4], [5], [6], [7], [8]

The protracted current

According to modern ideas, a protracted hepatitis should be understood as a pathological process characterized by persistent clinical, biochemical and morphological signs of active hepatitis, duration from 3 to 6-9 months. In hepatitis A, prolonged hepatitis is relatively rare. S.N. Sorinsoy observed a prolonged course of hepatitis A in 2.7% of patients, I.V. Shahgildyan - in 5,1, PA, Daminov - in 10%. The relatively wide range of fluctuations in the frequency of prolonged course of hepatitis A can be explained not only by the different composition of patients, but primarily by the unequal approach to diagnosis. To protracted hepatitis it is customary to include all cases of the disease, which lasts from 3 to 9 months. For hepatitis A, prolonged hepatitis should be diagnosed with a disease duration of more than 2 months.

In the patients with prolonged hepatitis A, the initial manifestations of the disease differed little from those in acute hepatitis. The disease, as a rule, began acutely, with the rise in body temperature to 38-39 ° C and the appearance of symptoms of intoxication. The duration of the pre-jaundice period averaged 5 + 2 soups. With the appearance of jaundice, the symptoms of intoxication usually weakened. The maximum severity of jaundice reached 2-3 days of 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 cyclicity was detected only in the period of early convalescence. At the same time, the size of the liver was prolonged for a long time, rarely - the spleen. In the serum, the activity of the liver of the full-cellular enzymes did not show a tendency toward normalization, and the indices of thymol test remained high. In a quarter of patients with a distinct initial positive dynamics of clinical and biochemical parameters in the reconvalescence period, the activity of ALT and F-1-FA increased again and the results of thymol test increased, with only insignificant cases (the amount of bilirubin not exceeding 35 μmol / l) and short-term jaundice.

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

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

The presented factual data show that the process of recovery with prolonged hepatitis A can be significantly prolonged and last more than 6 months. However, this does not give grounds to consider such forms of chronic hepatitis. At the heart of the emergence of protracted hepatitis A are the features of 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 changes in the immunoregulatory subpopulations. In this case, the T helper / T-suppressor ratio does not deviate from the normal values. The absence of a 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 the normal range, and the level of specific anti-HAV IgM class, although it increases, but insignificantly, only at the end of the 2nd month from the beginning there is 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 a factor of 1.5-2, and an increase in the level of specific anti-HAV IgM class. Such immunological changes led to a belated, but still complete elimination of the virus and recovery.

Thus, according to the nature of the immunological response, prolonged hepatitis A approaches acute hepatitis, it is only a feature that with it a delayed specific immunogenesis is observed and an elongated cycle of the infectious process is formed.

Current with exacerbation

The aggravation should be understood as the intensification of the clinical signs of hepatitis and the worsening of the indicators of functional liver samples against the backdrop of the remaining pathological process in the liver. The exacerbations should be distinguished from relapses - the recurrence (after a period of absence of visible manifestations of the disease) of the underlying syndrome of the disease in the form of enlargement of the liver, often spleen, the appearance of jaundice, an increase in body temperature, etc. Relapses can occur in the form of the jaundiced variant. Both exacerbations and relapses are always accompanied by an increase in the activity of hepatic cell enzymes. Relevant changes in sedimentary protein samples and other laboratory tests are detected. In a number of cases, there is only a deviation from the norm on the part of liver tests without any clinical manifestations of the disease. These are the so-called biochemical exacerbations.

The causes of exacerbations and relapses are not exactly established at present. Given that relapses occur in most cases in 2-4 months from the onset of hepatitis A, you can assume super infection with viruses of another type of hepatitis. According to the literature, in half of the cases during the relapse there is a transient HBs-antigenemia that testifies in favor of the layered hepatitis B. It is shown that during hepatitis B stratification during hepatitis A it is wavy due to enzymatic exacerbations, or relapses occur with a typical clinical picture hepatitis B. Research conducted in our clinic confirms the leading role of superinfection in the occurrence of relapses in hepatitis A. Almost in all patients with a hack called relapse, hepatitis We documented the HB virus superinfection and could not rule out the layering of viral hepatitis "neither A nor B".

However, if the question of the genesis of hepatitis A relapses is solved unambiguously by most researchers - the layering of another type of hepatitis, it is not always easy to understand the cause of exacerbations. Quite often, exacerbations of hepatitis A occur in patients with a so-called protracted convalescence, the network against the background of still persistent activity of hepatic cell enzymes and deviation from the norm of other hepatic tests. The increase in the activity of the pathological process in the liver in such cases occurs for no apparent reason and, as a rule, against the background of circulation in the blood of specific anti-HAV IgM class. It is possible to assume, of course, that in these cases another antigenic variant of the hepatitis A virus is infected, but still there are more reasons to believe that the main cause of the exacerbation is activation of the virus in a patient with functional immunodeficiency and a delay in a full immunological response, the level of specific antibodies about genesis and the 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 anti-HAV titer of IgA class in serum.

[9], [10], [11], [12], [13], [14]

The course with lesions of the biliary tract

In hepatitis A, the lesion of the biliary tract is usually accompanied by dyskinetic events that can be diagnosed in any period of the disease. The predominant type of dyskinesia is hypertonic, characterized by hypertension of the muscle-squeezer, increased tone of the cystic duct and gallbladder. These changes are noted for any form of hepatitis A, but more pronounced in moderate-to-severe forms, especially in patients with cholestatic syndrome.

In most foxes, kinetic phenomena in the biliary tract pass without any treatment as the symptoms of viral liver damage are eliminated, which allows them to be associated directly with HAV infection in the acute period of the disease. The defeat of the biliary tract in the acute period of hepatitis A does not significantly affect the course of the pathological process in the liver. The total duration of the disease in most cases fits within the framework of acute hepatitis. Only in rare cases, the defeat of the biliary tract is accompanied by a cholestatic syndrome. Often, the lesion of the biliary tract is revealed in the period of convalescence. Thus patients complain of periodically arising pains in a stomach, a nausea, sometimes a vomiting Often they have a belching on an empty stomach. With an objective examination, it is possible to detect the pain of the liver, mainly in the projection of the gallbladder. In some cases, there are positive "bubble" symptoms of hepatitis A and hepatomegaly without distinctive subjective complaints.

Flow with a layer of intercurrent diseases

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

In the literature, there is an opinion on the aggravating effects of intercurrent infections on the course of the disease, such as dysentery, pneumonia, typhoid fever, ARVI, measles, whooping cough, and helminthic invasion, gastroduodenitis, ulcerative colitis, and many others.

It should be noted, however, that most of the literature on the problem of hepatitis-mixed is unconvincing, since observations were made 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, 33% of cases were combined with other infections, including 23% of ARVI and 4% of urinary tract infection.

Significant influence of intercurrent diseases on the severity of clinical manifestations, the degree of functional disorders, as well as the nature of the course, the immediate and distant outcomes of hepatitis A are not observed. Only in some patients with the layering of the intercurrent disease, the liver size increased again, the activity of hepatic-peptide enzymes increased, the index of thymol test increased, and even the slowed pace of functional restoration of the liver. However, even in these patients, it was not possible to relate the marked changes exclusively to a lumpy infection. Obviously, the issue of the mutual influence of hepatitis A and concomitant diseases can not be considered fully resolved; in our opinion, there is no sufficient reason to exaggerate the significance of intercurrent diseases for the severity, nature of the course and outcomes of hepatitis A.

[15], [16], [17]

Classification of hepatitis A

Hepatitis A is classified by type, severity and course.

Severity indicators:

• clinical - increased body temperature, vomiting, decreased appetite, hemorrhagic manifestations, intensity of jaundice, enlarged liver;
• laboratory - the content of bilirubin, prothrombin, sulfate titer, etc.

A type	The form	Flow
		By duration	The 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 icteric staining of the skin and visible mucous membranes, to atypical - jaundice, erased and subclinical. Typical hepatitis A in severity can be of light form, moderate and severe. Atypical cases are usually of mild form.

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 reach maximum development, and the severity of the pre-egg period should be taken into account.

[18], [19], [20], [21], [22], [23]

Clinical forms of hepatitis A

Symptoms of general intoxication (fever, vomiting, adynamia, loss of appetite) in the initial, pre-jaundiced period, the more pronounced, the heavier the form of the disease. The short, pre-zheltushny period is characteristic of heavier forms. Particularly distinct differences in intoxication depending on the severity of the disease are detected in the icteric period. With a mild and moderate form of the disease with the appearance of jaundice, the symptoms of intoxication significantly weaken or even completely disappear. In severe forms with the appearance of jaundice, the condition of patients, on the contrary, worsens due to the appearance of "exchange", or secondary, toxicosis. Patients complain of headache, dizziness, general weakness, lack of appetite.

Objective criteria for the severity of viral hepatitis in patients are the degree of increase in liver size and intensity of jaundice.

[24], [25], [26], [27],

The moderate form of hepatitis A

Occurs in 30% of patients. It is characterized by moderately expressed symptoms of intoxication. In the pre-zheltushnom period, the body temperature rises to 38-39 ° C for 2-3 days. Characteristic lethargy, mood changes, dyspeptic. Phenomena (nausea, vomiting), abdominal pain, sometimes upset of the chair. The duration of the pre-jaundice period averaged 3.3 ± 1.4 days. That is, it is shorter than with mild forms of the disease. With the appearance of jaundice, the symptoms of intoxication, although weaken, but persist; lethargy and decreased appetite - in all, nausea, sometimes vomiting - in a third, subfebrile body temperature - in half of patients. Jaundice from moderate to severe, in rare cases itchy skin is possible. The liver is painful, its edge is dense, protruding from under the costal arch for 2-5 cm. The spleen is enlarged in 6-10% of patients, palpable at the edge of the costal arch. Often marked bradycardia and often - hypotension. The amount of urine is reduced.

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

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

Severe form of hepatitis A

When hepatitis A occurs extremely rarely, not more often than in 5% of patients. It seems that heavier forms of hepatitis A are encountered more often at the waterway of infection.

Distinctive signs of severe form are intoxication and marked biochemical shifts in blood serum. The disease always begins sharply with the rise in body temperature to 39-40 ° C. From the first days are characterized by weakness, anorexia, nausea, repeated vomiting, abdominal pain, dizziness, upset of the chair. The pre-egg period is often short-2-3 days. With the appearance of yellows, the condition of patients remains severe. Patients complain of general weakness, headache, dizziness, a complete lack of appetite. Jaundice increases rapidly, during the day, usually bright, but itching does not happen. On the skin, hemorrhagic eruptions are possible, they usually appear on the neck or shoulders after the harness is applied due to intravenous manipulation. Tones of the heart are muffled, the pulse is increased, blood pressure tends to decrease. The liver is sharply enlarged, palpation is painful, the spleen is enlarged.

The content of total bilirubin in the serum is more than 170 μmol / l. Advantageously, the level of conjugated bilirubin is increased, but 1/3 of the total bilirubin is the free fraction. The prothrombin index is reduced to 40%, the subleum titer is up to 1.4 DB, the activity of organ-specific hepatic cell enzymes is dramatically increased, especially in the pre-zheltushnom period and in the early days of jaundice. The disease runs smoothly. The protracted current practically does not occur.

Anzheltushnaya form of hepatitis A

A distinctive feature of this form of the disease is the complete absence of hysterical skin and sclera throughout the entire disease. With a purposeful examination of groups in epidemic foci of hepatitis A, jaundice forms are diagnosed 3-5 times more often than icteric forms.

The clinical manifestations of an icteric form do not differ much from those with mild typical forms.

For jaundice forms of hepatitis A, a combination of dyspeptic and asthenovegetative symptoms with increasing liver size, as well as a change in the color of urine due to an increase in the concentration of urobilin and bile pigments are characteristic. In the blood serum, there is always an increased activity of hepatic cell enzymes (ALT, ACT, F-1-FA, etc.), significantly increased the indices of thymol test, the content of conjugated bilirubin is often increased, but the total bilirubin level does not exceed 35 μmol / l. The prothrombin index and the mercury titer are always within the normal range. The clinical symptoms of hepatitis A, with the exception of the increase in liver size, as well as the disruption of biochemical parameters, are kept for a short time with anicteric forms. The general condition of the patient is practically not disturbed, and therefore, with insufficient close monitoring, the patient can tolerate the disease on his legs while remaining in the team.

[28],

Shabby form

The erased form includes cases of viral hepatitis with mildly expressed underlying symptoms of the disease. A distinctive sign of an erased form is the barely noticeable icterus of the skin, visible mucous membranes and sclera that disappears after 2-3 days. With an erased form, the symptoms of hepatitis A of the initial (prodromal) period are slightly or absent. Possible short-term (1-2 days) increase in body temperature, lethargy, weakness, deterioration of appetite: an increase in liver size is negligible. With great consistency, but briefly observed dark urine and discolored feces. In the blood, a moderately elevated activity of hepatic cell enzymes is found. The content of total bilirubin is slightly increased due to the conjugated (direct) fraction. The indices of thymol test were increased by 1.5-2 times. In general, clinico-biochemical manifestations with erased form can be characterized as a facilitated, rudimentary variant of a mild, typical form having abortive flow. Its significance, as well as the jaundiced form, lies in the difficulty of recognition, with the resulting epidemiological consequences.

Subclinical (inapparant) form

With this form, in contrast to the jaundice and blurred, there are no clinical manifestations. The diagnosis is made only in the laboratory examination of those who are in contact with patients with viral hepatitis. Of the biochemical samples, the most important for the diagnosis of such forms are the parameters of enzymatic activity and, first of all, the increase in the serum of the activity of ALT and F-1-FA; less ACT activity is increased and positive thymol test is detected. In all patients with a subclinical form of hepatitis A, specific antibodies are detected in the blood-anti-HAV of the IgM class, which is crucial for the diagnosis. It is widely believed that in the hepatitis A focus most patients become infected and suffer a predominantly inapparent form of the disease. In the foci of hepatitis A, one disease diagnosed clinically and using biochemical samples is detected on average by 5-10 patients with hepatitis A virus in feces. It is shown that if the contact in the foci of hepatitis A is examined with the help of only biochemical tests, the disease is detected on average in 15%, whereas in the application of virological methods - in 56 and even 83% of the contact ones.

The large prevalence of subclinical forms of hepatitis A is evidenced by the fact that among patients who have anti-HAV IgM class, only 10-15% suffer the icteric form of the disease. The importance of inpatient subclinical forms of hepatitis A is that, while remaining unrecognized, they, like the jaundiced forms, serve as an invisible link that constantly supports the chain of the epidemic process.

Viral hepatitis A with cholestatic syndrome

In this variant of viral hepatitis, the symptoms of mechanical jaundice appear in the clinical picture. There is reason to believe that this form of the disease has no clinical independence. The syndrome of cholestasis can occur both with the easiest, and with more severe forms of the disease. At the heart of its development is bile retention at the level of intrahepatic bile ducts. It has been suggested that bile retention occurs due to damage to cholangiol by the virus itself. Many authors have pointed 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, and the karyolysis of the nuclei of the cells of the ductular epithelium are observed. Inflammatory changes in intrahepatic bile ducts, their increased permeability, bile diapedesis, increase in its viscosity lead to the formation of thrombi, large crystals of bilirubin; there are difficulties in the movement of bile through the bile capillaries and cholangiols. To a certain extent intracanular bile retention is associated with pericholangiolitic and periportal infiltration, which occurs as a consequence of hyperergic disorders. It is also possible to exclude the involvement of hepatocytes themselves in this process, namely, to increase 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.

With reference to the cholestatic form of viral hepatitis, the point of view of the authors of the past is not without foundation. According to her, the main cause of cholestasis is a mechanical obstruction that occurs at the level of the bile ducts, the gallbladder and even the contractile muscle 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 choleletase", "cholangiolytic hepatitis", "hepatitis with long bile retention" and t .

The literature data on the frequency of the cholestatic form of viral hepatitis are very contradictory: from 2.5 to 10%.

The leading clinical symptom for 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, jaundice has a greenish or a saffron tinge, but sometimes jaundice of the skin can be mild, and in the clinical picture itchy skin dominates. Symptoms of intoxication with a cholestatic form are absent or they are weakly expressed. Dimensions of the liver increase slightly. Urine is usually dark, and the cap is discolored. In serum, the bilirubin content is usually high, solely due to the conjugated fraction. The activity of liver enzymes from the first days moderately increases, and then, despite the high content of bilirubin in the serum, decreases almost to normal values. The high content of beta-lipoproteins, total cholesterol, as well as a significant increase in the serum activity of alkaline phosphatase and leucine aminopeptidase can be considered characteristic of the cholestatic form. The indices of other functional tests (the sample assay, the level of coagulation factors, thymol assay, etc.) vary slightly or remain within the normal range.

The course of hepatitis A with cholestatic syndrome, although long-lasting, but always favorable, leads to a complete restoration of the functional state of the liver. Chronic hepatitis is not formed.

Outcomes of hepatitis A

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

Recovering with complete restoration of liver structure and function

According to one clinic clinic, of the 1158 children who underwent hepatitis A, by the time of discharge from the hospital (25-30 days of the disease), 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 6 months after the onset of the disease, various effects of hepatitis A were revealed, including 4.4% - enlargement and consolidation of the liver with complete preservation of its functions, 7.2% - abdominal pain due to dyskinesia biliary tract (3%), cholecystitis or cholangitis 0.5%), gastroduodenitis (2.5%), pancreatopathy (0.2%). In no case was the formation of chronic hepatitis observed.

Recovery with an anatomical defect, post-hepatitis hepatomegaly (residual fibrosis).

A prolonged or life-prolonging increase in liver size after a hepatitis A with complete absence of clinical symptoms and laboratory changes is possible. The morphological basis of hepatomegaly is residual liver fibrosis. At the same time, dystrophic changes on the part of hepatocytes are completely absent, but the proliferation of Kupffer cells and the coarsening of the stroma are possible. It should, however, be noted 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 after 1 month after discharge from the hospital is noted in 32.4% of children, after 3 months in 24, and after 6 months in 11.6% of patients. In all these patients, the liver protruded from the edge of the costal arch 1.5-2.5 cm and was painless, and biochemical tests indicated a complete restoration of its functional activity. On formal grounds, such an increase in liver size could be treated as residual liver fibrosis in the outcome of hepatitis A. However, with a careful study of the anamnesis and as a result of a purposeful examination (ultrasound, immunological tests, etc.) in most of these patients, the increase in liver size was regarded as a constitutional feature or as a result of previous illnesses. Only 4.5% of patients documented residual fibrosis in the outcome of hepatitis A.

Lesion of the biliary tract

The defeat of the biliary tract is more correctly interpreted not as an outcome, but as a complication of hepatitis A, which is a result of a combined lesion of biliary tract virus and a secondary microbial flora. By its nature, this is a diekinetic or inflammatory process. Often it is combined with the defeat of other departments of the gastrointestinal tract, gastroduodenitis, pancreatitis, enterocolitis.

Clinically, the lesion of the biliary tract manifests itself in a variety of complaints (pain in the right hypochondrium or epigastrium, often recurrent or paroxysmal, associated with the intake of food, sometimes a feeling of heaviness or pressure in the right upper quadrant, nausea, vomiting). As a rule, abdominal pains appear 2-3 months after the transferred hepatitis A.

Among the 1158 patients with hepatitis A, abdominal pain at 6 months from the onset of the disease was noted in 84 cases, which is 7.2%. All these patients, along with moderate hepatomegaly, had complaints of abdominal pain, nausea, sometimes vomiting, belching or fasting food, palpation showed pain in the epigastric region. Some patients showed positive "vesicle" symptoms and hepatomegaly without distinctive subjective complaints. A comprehensive clinical and laboratory examination made it possible to exclude the formation of chronic hepatitis in all these patients. To clarify the diagnosis, they were thoroughly examined in the conditions of the gastroenterological center with the use of modern research methods (fibrogastraduodenoscopy, colonoscopy, irrigoskonia, fractional study of gastric juice, duodenal sounding, etc.).

When analyzing the anamnestic data, it was found that half of the patients had complaints of abdominal pain and dyspeptic disorders before hepatitis A. Some patients were treated in somatic hospitals for chronic gastroduodenitis, biliary dyskinesia, chronic colitis, etc. The duration of these diseases before the onset hepatitis A was 1-7 years. In the early periods of convalescence (after 2-4 weeks after discharge from the hepatitis hospital), all of these patients again developed abdominal pain and dyspeptic symptoms of hepatitis A. At the examination, the majority was diagnosed with exacerbation of chronic gastroduodenitis. In 82% of cases, changes in the mucous membrane of the stomach and duodenum were detected in PHEGS. In some cases, in the absence of endoscopic signs of lesion, functional disorders of the acid and secretion-forming function of the stomach are revealed. Often there was a combined pathology of the gastroduodenal system, intestines and bile ducts.

A retrospective analysis of the anamnestic data showed that the majority of these patients (62%) had a hereditary 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 hepatitis A. The pains appeared 2-3 months after the onset of hepatitis and were of a different nature, usually at an earlier time after eating, less often later, or were permanent. As a rule, pains arose due to physical exertion, they had a paroxysmal or aching character. From dyspeptic phenomena, nausea was usually observed, less often - vomiting, unstable stools, belching, heartburn, constipation.

Clinical examination revealed morbidity during palpation in the epigastric and pyloroduodenal region, in the right hypochondrium and at the gallbladder point. In all these patients, an increase in the size of the liver (the lower edge protruding from the rib arch was 2-3 cm) and positive "cystic" "Symptoms of hepatitis A. Endoscopy in 76.7% of patients showed signs of damage to the mucous membrane of the stomach and duodenum. In 63% of cases the pathology was combined (gastroduodenitis), and in 16.9% - isolated (gastritis or duodenitis). Only 17.8% of patients visually showed no changes in the mucous membrane of the stomach and duodenum. However, in a fractional study of gastric juice, a part of them showed violations of the acid and secretion-forming function of the stomach.

In the overwhelming majority of cases (85.7%), along with the lesions of the gastro-duodenal zone, dyskinetic disorders of the gallbladder have been identified. 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 events or long-term effects in the form of long-lasting symptoms of general asthenia, vague abdominal pain, enlargement of the liver, dyspeptic complaints and other manifestations, which in practical work have been interpreted as "post-hepatitis syndrome", are identified in hepatitis A convalescents , with a careful targeted examination in most cases, deciphered as a chronic gastroduodenal or hepatobiliary pathology, revealed silt arose in connection with hepatitis A. This is why the presence of complaints of abdominal pain, heartburn; nausea or vomiting in the period of convalescence of hepatitis A it is necessary to conduct an in-depth examination of the patient for the purpose of revealing the pathology of the gastroduodenal and biliary systems. Such convalescents should be observed in a gastroenterologist and receive appropriate therapy.

Posthepatic hyperbilirubinemia

Post-hepatitis hyperbilirubinemia can only be conditionally associated with a previous viral hepatitis. According to modern ideas, this syndrome is caused by a hereditary bilirubin exchange defect, which leads to a disruption in the transformation of unconjugated bilirubin or impaired excretion of conjugated and as a consequence to the accumulation in the blood of the indirect fraction of bilirubin (Gilbert's syndrome) or direct fraction (Rotor, Dabin-Johnson syndromes, ). 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, SARS, etc.

In the outcome 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 often occurs in boys in the puberty period. The leading clinical symptom of hepatitis A is mild jaundice due to a moderate increase in the blood of unconjugated bilirubin (usually no more than 80 μmol / l) with no symptoms characteristic of hemolytic jaundice and viral hepatitis. The same can be said for the syndromes of Rotor and Dabin-Johnson, with the only peculiarity that in the blood in these cases the content of exclusively conjugated bilirubin is increased.

Chronic hepatitis in the outcome of hepatitis A is not formed.

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