Hepatitis B: symptoms

With hepatitis B, all types of infectious process are possible - from healthy carriage of HBV erased and subclinical forms to severe manifest forms, including malignant, leukemia and lethal outcome. The clinical symptoms of hepatitis B in general resemble hepatitis A. There are also four periods: incubation, initial (pre-jaundice), midsummer and convalescence, but these periods differ significantly in the content of these hepatitis.

[1], [2], [3], [4], [5], [6], [7], [8]

Symptoms of hepatitis B in the initial (doc inclusive) period

The disease begins gradually. The increase in body temperature is not always noted and usually not on the first day of illness. Characteristic symptoms of hepatitis B, such as lethargy, weakness, rapid fatigue, decreased appetite. Often, these symptoms are so weak that they can be seen, and the disease as it begins with a darkening of the urine and the appearance of discolored feces. In rare cases, the initial symptoms are pronounced; nausea, repeated vomiting, dizziness, drowsiness. Often there are dyspeptic disorders: flatulence, constipation, less often diarrhea. Older children and adults complain of dull pain in the abdomen. At objective examination in this period the most constant symptoms are general asthenia, anorexia, enlargement, compaction and tenderness of the liver, as well as darkening of urine and often discoloration of feces.

Frequency of symptoms of the initial period with acute hepatitis B

Symptom	Frequency,%
	Children of the first year of life	Children over 1 goal	Adults
Sharp beginning	57.6	34.5	15
Gradual Beginning	42.4	65.5	85
Lethargy, weakness, fatigue, adynamia	42.4	61.5	100
Musculoarticular pain	-	1.3	18
Temperature increase	52.2	39.8	82
Decreased appetite, anorexia	63.9	58.4	90
Nausea, regurgitate	14	18.9	45
Vomiting	37.4	34.1	32
Stomach ache		44.0	55
Cataracts	18.5	12.1	28
Diarrhea	12.7	11.4	15
Hemorrhagic skin rashes	2.5	1-3	1.5
Allergic rash	2.5	8.8	2

Hepatitis B in the initial, prodromal, period most often manifests itself as symptoms of general infectious toxicosis (lethargy, weakness, adynamia, anorexia, etc.). Half of patients have an increase in body temperature, but, as a rule, not to high values, only in individual patients we observed an increase in body temperature to 39-40 ° C. Usually these were children of the first year of life, who developed a fulminant form of the disease. To frequent symptoms of the initial period of hepatitis B include dyspeptic phenomena: a decrease in appetite, down to anorexia, aversion to food, nausea, vomiting. These symptoms of hepatitis B usually manifest from the first days of the disease and are found throughout the initial (pre-jaundiced) period.

Musculo-articular pains often appear in adult patients; in children, they are very rare in the pre-jaundice period. Among the observed diseased children, only 1.3% of the cases were observed. Half of them complained of abdominal pains that were more often localized in the epigastric region, less often in the right hypochondrium or were spilled.

Rarely in the pre-zheltushnom period observed skin rashes, flatulence, upset of the chair.

Catarrhal phenomena are generally not characteristic for hepatitis B, among the patients we observed, they were noted in 15% of cases, manifested by coughing, mucous discharge from the nose, diffuse hyperemia of the mucous membrane of the oropharynx. In all these patients catarrhal phenomena are not associated with hepatitis B, as in most cases it can be assumed that ARVI or mixed infection has been associated since the first days of the disease.

The most objective symptom in the initial period is the enlargement, compaction and soreness of the liver. This symptom we observed in all patients in those cases when it was possible to follow the development of clinical symptoms from the first day of the disease. The increase in liver size usually starts from the 2nd-3rd day after the onset of the disease, a little earlier the soreness is revealed on palpation of the right hypochondrium, sometimes even out of connection with the increase in liver size. The enlargement of the spleen was observed only in single patients immediately before the appearance of jaundice.

Changes in peripheral blood in the initial period of hepatitis B are not characteristic. One can only note a small leukocytosis, a tendency to lymphocytosis; ESR is always within normal limits.

In all patients already in the pre-jaundiced period, the serum of the blood shows a high activity of ALT, ACT and other hepatic-cellular enzymes; at the end of this period, the content of conjugated bilirubin increases in the blood, but the values of sediment samples do not usually change and there is no disproteinemia. The blood circulates in high concentrations of HBsAg, HBeAg and anti-HBc IgM and often reveals the DNA of the virus.

The duration of the initial (pre-jaundiced) period can vary in a wide range - from a few hours to 2-3 weeks; in observations it averaged 5 days. The maximum duration of the pre-jaundice period in the patients was 11 days, but in 9.9% of the patients there was no pre-egg period at all, and the disease in these cases began immediately with the appearance of jaundice.

Symptoms of hepatitis B in the icteric period (the height of the disease)

1-2 days before the appearance of jaundice, all patients have darkening of the urine and the majority - bleaching feces. Unlike hepatitis A, in case of hepatitis B, the transition to the third (icteric) period in most cases is not accompanied by an improvement in the general condition and, on the contrary, in many patients with jaundice the symptoms of intoxication are intensified. In 33% of patients on the first day of icteric period, subfebrile body temperature is observed, 25% - nausea, vomiting, 9.3% of patients complain of abdominal pain, full anorexia. Patients remain sluggish, complain of general weakness, poor appetite, bitter taste, bad smell from the mouth, a feeling of heaviness or pain in the right hypochondrium, zpigastria or without specific localization.

Jaundice with hepatitis B is increasing gradually - usually within 5-6 days, sometimes up to 2 weeks and longer. The icteric color can vary from slightly yellow, canary or lemon to a greenish-yellow or ocher-yellow, saffron color. The degree of jaundice and its shade are associated with the severity of the disease and the development of cholestasis syndrome. Having reached the peak of severity, jaundice with hepatitis B usually stabilizes for 5-10 days, and only after this begins to decrease.

The frequency of symptoms of icteric period in patients with acute hepatitis B

Symptom	Frequency,%
	Children of the first year of life	Children over 1 year old	Adults
Lethargy, weakness, adynamia	74	64.7	98
Decreased appetite, anorexia	75.3	68.3	100
Increased body temperature	32.9	0	2
Nausea, regurgitation	25.1	-	50
Vomiting	41.6	5.4	25
Stomach ache	0	Eleven	55
Hemorrhagic rash	26.7	18.2	20
Rashes on the skin	-	7.8	2
Diarrhea	0	0	15
Increased liver size	100.0	95	98
Increased Spleen Size	96.3	49.3	15

As can be seen from the presented data, in the icteric period practically all patients have symptoms of asthenovegetative and dyspeptic character. The degree of their severity and the duration of detection are directly dependent on the severity of the disease and to a lesser extent on age. At the same time, attention is drawn to the complete absence of symptoms characteristic of hepatitis B in adults in adults, such as musculo-articular pain, diarrhea, catarrhal phenomena, and rarely itchy skin.

A rare symptom of hepatitis B can be considered a rash on the skin. In clinical observations at the height of jaundice, skin rashes were in 7.8% of patients in the group of older children. The rash was located symmetrically on the limbs, buttocks and trunk, was spotted-papular, red in color, with a diameter of up to 2 mm. When the rash was applied, the rash was ocher-colored, after a few days, weak peeling appeared in the center of the papules. These rashes should be interpreted as the Gianotti-Crosti syndrome, described by the Italian authors in hepatitis B.

In severe cases in the height of the disease, there may be manifestations of hemorrhagic syndrome: point or more significant hemorrhages in the skin. It should be noted, however, that in the expanded form hemorrhagic syndrome with hemorrhages on the skin and bleeding from the mucous membranes is observed only in hepatic insufficiency associated with massive or submissive necrosis of the liver.

In parallel with the growth of jaundice in hepatitis B, the liver grows in size, its edge becomes denser, palpation becomes painful.

An increase in liver size in typical cases of hepatitis B is observed in almost all patients (96.3%), with the liver increasing evenly with the predominance of lesion of the left lobe.

The increase in the spleen is less common than in the liver, in the observations - in 96.3% of children in the first year of life and in 49.3% in older children. The spleen is more often in more severe cases and with a prolonged course of the disease. According to studies, in light forms, the spleen is palpable in 65%, in the middle forms - in 72, and in severe forms - in 93% of patients. Enlargement of the spleen is noted throughout the acute period with a slow reverse dynamics, often the spleen is palpable and after the disappearance of other (excluding liver enlargement) symptoms of hepatitis B, which usually indicates a prolonged or chronic course of the disease.

The most characteristic changes in the cardiovascular system with hepatitis B are bradycardia, vagal-type respiratory arrhythmia, lowering of arterial pressure, weakening of tones, impurity of 1 tone or mild systolic murmur at the apex, slight accentuation of tone II on the pulmonary artery, sometimes - short-term extrasystole.

In the initial period of the disease, cardiac activity is increased. In the icteric period, there is a bradycardia with arrhythmia. With the disappearance of jaundice, the pulse rate gradually approaches the norm, remaining for some time labile. Sudden change at the altitude of jaundice bradycardia on tachycardia should be regarded as an unfavorable symptom, indicating the danger of developing a hepatic coma.

Cardiovascular changes in hepatitis B almost never play a major role in the course and outcome of the disease. In the overwhelming majority of cases, cardiac activity is normalized by the time of discharge.

Electrocardiographic changes in hepatitis B in the form of compaction and reduction of the T wave, minor QRS complex broadening, decrease of the ST interval, sinus respiratory arrhythmia are treated as manifestations of functional cardiac disorders, and not as an indicator of myocardial damage. In fact, these changes can be considered a manifestation of the "infectious heart", very often observed in other infectious diseases. Moreover, more pronounced electrocardiographic changes, sometimes found in severe forms of hepatitis B, can be the result of direct toxic effects on the heart muscle, as well as the reflection of metabolic disorders in the body and heart muscle.

Changes in the nervous system in the clinical picture of hepatitis B occupy a prominent place, they are all the more noticeable and brighter, the stronger the damage to the liver. However, even in mild cases, even at the onset of the disease, one can detect some common CNS depression, manifested in a change in the mood of patients, decreased activity, lethargy and adynamia, sleep disturbances and other manifestations.

In severe cases, very severe cerebral disorders are associated with significant dystrophic changes in the liver. It is with these forms that pronounced anatomical changes are described in the nervous system with the largest lesion of the subcortical nodes, where the vegetative centers are localized.

In hematological studies in the early stages of the icteric period, an increase in the number of erythrocytes and the amount of hemoglobin is usually observed, but at the jaundice height the number of erythrocytes tends to decrease. In severe cases, anemia develops. The percentage of reticulocytes at the height of the disease is usually elevated. In rare cases, more severe changes in the bone marrow are possible, up to the development of panmyelophthosis.

The number of leukocytes in the icteric period is normal or decreased. In the blood formula at the height of toxicosis, the incidence toward neutrophilia is revealed, and in the period of recovery to lymphocytosis. A third of patients with monocytosis. In severe cases, moderate leukocytosis with a stab-shift shift is particularly common, with ESR almost always decreasing, whereas in mild forms of ESR it is usually within the normal range. Low ESR (1-2 mm / h) with severe intoxication in a patient with severe hepatitis B is an unfavorable sign.

At the height of the disease in the blood serum, the total bilirubin content (mainly due to the conjugated fraction) is maximally increased due to a violation of its excretion by hepatocytes. Mechanisms of capture and conjugation of bilirubin are violated only in severe forms and especially with massive necrosis of the liver. In these cases, along with the increase in conjugated bilirubin, the amount of unconjugated fraction increases in serum.

An increase in the activity of hepatic-cellular enzymes in the icteric period is noted in all patients. The maximum activity of ALT and AST is usually recorded at the height of the icteric period, then the activity begins to gradually decrease with complete normalization towards the end of the 6-8th week of the disease and not in all patients.

In most patients, the amount of total protein decreases in the serum due to the decreased synthesis of albumins, in a number of cases the content of al- and a2-globulins increases, and in most cases the content of y-globulins increases, but still pronounced disproteinemia at the height of the disease is observed only in severe cases and malignant forms of the disease.

The indices of thymol test for hepatitis B are often normal or slightly elevated.

Indicators of the sulemic test for hepatitis B tend to decrease, a significant decrease is observed only in severe cases, especially in malignant forms and cirrhosis of the liver.

Indicators of beta-lipoproteins in the acute period of the disease increase by 2-3 times or more, as the recovery and normalization of other biochemical tests gradually decrease to normal. With the development of massive liver necrosis, the beta-lipoprotein index decreases sharply, which is a poor prognostic sign.

At the height of the disease with hepatitis B, the prothrombin index, fibrinogen, and proconvert levels decrease, especially in severe forms accompanied by massive or submissive liver necrosis. The drop in the prothrombin index to zero values always indicates an unfavorable prognosis.

In the icteric period, HBsAg, HBeAg, and anti-HBC IgM continue to be detected in the blood, and antibodies to the cow antigen of the IgG class and anti-HBV appear in some patients. Of other immunological changes at the height of clinical manifestations, a slight decrease in T-lymphocytes, especially of T-lymphopitol-helpers, at a relatively normal level of T-lymphocytes-suppressors is revealed at a high level of clinical manifestations, T-lymphocyte sensitization to HBsAg and hepatic lipoprotein, the content of B-lymphocytes tends to increase, the content of immunoglobulins IgM and IgG increases.

The noted immunological shifts are stable, they can be traced throughout the acute period and are more pronounced in severe forms of the disease.

The incubation period of hepatitis B

The incubation period for hepatitis B is 60-180 days, usually 2-4 months, in rare cases is reduced to 30-45 days or grows up to 225 days. The duration of the incubation period depends on the infectious dose and possibly on the age. With a massive infection, which is usually observed with blood or plasma transfusions, a shorter incubation period is observed - 1.5-2 months, whereas with parenteral manipulations (subcutaneous and intramuscular injections) and especially with domestic infection, the incubation period is usually 6 months. In children of the first months of life, the duration of the incubation period is usually shorter than 2.8 ± 1.6 days) than in children of older age groups (117.8 ± 2.6, p <0.05).

Clinical symptoms of hepatitis B are completely absent in this period. But as in hepatitis A, at the end of the incubation in the blood, a high activity of hepatic cell enzymes is constantly detected and, in addition, you are markers of actively active HBV virus infection: HBsAg, HBeAg ;, anti-HBc IgM.

Signs of hepatitis B in the convalescent (recovery) period

The total duration of icteric period with hepatitis B varies widely - from 7-10 days to 1.5-2 months. In the observations, the jaundice period averaged 29.5 ± 12.5 days, including 20.6 ± 9.6 days for mild forms, 31.4 ± 13 for the moderate forms, and 31.6 ± 16 for the severe ones day.

With the disappearance of jaundice, patients no longer complain, they are active, they regain their appetite, but in half the cases, hepatomegaly remains, and in 2/3 - a slight hyperfermentemia. It may be noted that even in the context of a favorable course, cases with an accelerated rate of functional restoration of the liver are possible, when complete disappearance of clinical symptoms and normalization of functional liver samples occur 3-4 weeks later, and on the contrary, there are cases when the normalization of the clinical picture and biochemical changes does not occur after 4-6 months.

Investigating the rate of functional restoration of the liver in 243 patients with acute hepatitis B with the help of a universal curve reflecting the pattern of recovery processes in this disease, doctors noted that in 6.2% of cases, an accelerated rate of functional recovery (on average 25% per day), in 48 , 1 - the normal rate within the confidence intervals of the universal curve (on average 13% per day), in 41.7 - a slowed rate with a recovery rate of 7.5% per day, in 4% the rate of functional recovery will be 3.3% per day , that cla reclassified by us as a prolonged duration of hepatitis B.

The dynamics of clinical recovery correlated with the rate of functional restoration of the liver. At an accelerated rate of deceleration, clinical recovery was not observed, at a normal rate, in 18.8% of children under the age of one year and 10.3% in the elderly, and in delayed cases, in 57.4% and 40.6%, respectively.

Particularly pronounced deviations in the dynamics of clinical recovery were observed in patients with prolonged course of hepatitis B.

It is important to note that the slowing of the dynamics of clinical recovery in children of the first year of life occurred mainly due to the severity and duration of symptoms of intoxication and hepatomegaly, whereas in older children - due to the torpid current of jaundice. In some cases, the slowing down of the rate of functional recovery is associated with the presence of exacerbations, which in our observations in children of the first year of life were clinically more pronounced, whereas in children of the older age group they were usually manifested by an increase in the activity of hepatic cell enzymes.

In the convalescence period, serum HBsAg and, especially, HBeAg, are usually not detected in the blood serum, but anti-HBe, anti-HBc IgG and often anti-HBs are always detected.

The course of hepatitis B

In accordance with the generally accepted classification, the course of hepatitis B can be acute, protracted and chronic.

Acute course of hepatitis B

Acute course of hepatitis B is observed in 90% of patients. In these cases, the acute phase of the disease ends by the 25th and 30th days from the onset of the disease, and in 30% of cases, a complete recovery can be noted by this time. In the remaining patients, a slight increase in the size of the liver (no more than 2 cm below the edge of the costal arch) is noted in combination with hyperfermentemia, which exceeds the normal values by no more than 2-4 times. After 2 months from the onset of the disease, incomplete completion of the pathological process is observed only in 50% of patients, and only a third of them have an insignificant hyperfermentia; in others, there are enlarged liver sizes in combination with disproteinemia.

On the 3-4th month of the onset of the disease, complete recovery is noted already in 63%, and at the 6th month - in 93% of cases. The remaining patients have a slight increase in liver size, sometimes they continue to complain of a decrease in appetite, unstable abdominal pain, usually associated with eating or exercise. At the same time, the activity of liver-cell enzymes and other biochemical parameters remain normal.

In-depth examination of these patients in a gastrocentral environment in a third of them, a small hepatomegaly can be treated as an individual constitutional feature that is not associated with hepatitis B, all others document different gastroduodenal and hepatobiliary pathologies. Most often, these patients showed dyskinesia of bile ducts in combination with gallbladder deformation, cholecystocholangitis, gastroduodenitis or cholecystitis, but often these patients suffered from chronic gastroduodenitis, chronic enterocolitis, etc.

A retrospective analysis of anamnestic data showed that 30% of children subject to gastroenterology received subjective complaints (nausea, loss of appetite, eructation, etc.) before hepatitis B. The duration of these complaints ranged from 1 to 7 years. Half of the children had no complaints before hepatitis B, but with careful collection of the anamnesis, it turned out that they had either hereditary heredity, or polyvalent allergies (food, medicinal), or transferred infectious diseases (intestinal infections, mumps, etc.).

In the remaining children, subjective complaints and objective symptoms of gastroenteric pathology first appeared in hepatitis B or 1 -2 months after discharge from the hospital, which would seem to confirm their etiopathogenetic connection with the transferred liver disease, but given the nature of endoscopic changes, there are more reasons to think about a chronic, latent, ongoing gastroduodenal pathology, manifested under the influence of HBV virus infection.

[9], [10], [11], [12], [13], [14], [15], [16]

The protracted course of hepatitis B

According to research, a protracted course is observed in 7.8% of children. In these cases, hepatomegaly and hyperfermentemia persist for 4-6 months.

In protracted course, it is common to distinguish between three variants of the disease:

• The manifestation of protracted hepatitis is characterized by prolonged clinical and biochemical manifestations of the acute period: jaundice, hepatomegaly, hyperfermentation, etc. ("jam" in full swing).
• Persistent prolonged hepatitis is accompanied by long clinical and biochemical manifestations of the disease, characteristic of the period of its reverse development ("stuck" in the stage of reverse development). Jaundice is absent, the main manifestations of the disease are moderately expressed, hyperfermentemia is monotonous. The main symptoms of the disease are moderate hepatomegaly, less often splenomegaly.
• Wave-shaped lingering hepatitis manifests itself by repeated exacerbations occurring with a clinical picture, or only by an increase in the activity of enzymes.

In the patients with prolonged hepatitis B, complete clinical and laboratory recovery by seroconversion of HBsAg to anti-HBs occurred 6-10 months after the onset of the disease, in isolated cases, even after 1.5-2 years. Formation of chronic hepatitis B in the outcome of the manifest forms of hepatitis B was not observed in any case.

Classification of hepatitis B

Hepatitis B is also classified as hepatitis A, by type, severity and course.

However, the group of "gravity", along with light, medium and heavy, includes a malignant form that occurs almost exclusively with hepatitis B and D, and in the "flow" group, in addition to acute and prolonged, a chronic course is added.

Clinical and laboratory criteria for the identification of anicteric, erased, subclinical forms, as well as of mild, moderate and severe forms with hepatitis B do not fundamentally differ from those in hepatitis A.

• Clinical forms: icteric, jaundiced, subclinical (inapparant) variants.
• By the duration and cyclicity of the current.
  • Acute (up to 3 months).
  • Prolonged (more than 3 months).
  • With relapses, exacerbations (clinical, enzymatic).
• Forms by gravity.
  • Light.
  • The middle-aged.
  • Heavy.
  • Fulminant (fulminant).
• Complications: acute and subacute liver dystrophy with the development of hepatic encephalopathy and hepatic coma.
• Outcomes.
  • Acute hepatitis B, convalescence, chronic hepatitis B, lethal outcome with the development of liver dystrophy.
  • Chronic hepatitis B: recovery (spontaneous seroconversion of HBsAg / anti-HBs), inactive carriage, cirrhosis, hepatocellular carcinoma.

[17], [18], [19], [20], [21], [22]