Hepatitis B: symptoms

With hepatitis B, all types of the infectious process are possible - from healthy carriage of HBV erased and subclinical forms to severe manifest forms, including malignant ones, occurring with hepatic coma and a fatal outcome. Clinical symptoms of hepatitis B in general resemble hepatitis A. Four periods can also be distinguished: incubation, initial (pre-icteric), peak and convalescence, but in terms of content, these periods for these hepatitises differ significantly.

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Symptoms of hepatitis B in the initial (pre-icteric) period

The disease begins gradually. An increase in body temperature is not always observed and usually not on the first day of the disease. Symptoms of hepatitis B are lethargy, weakness, rapid fatigue, loss of appetite. Often these symptoms are so weak that they are visible, and the disease seems to begin with darkening of urine and the appearance of discolored feces. In rare cases, the initial symptoms are sharply expressed: nausea, repeated vomiting, dizziness, drowsiness. Dyspeptic disorders often occur: flatulence, constipation, less often diarrhea. Older children and adults complain of dull pain in the abdomen. During an objective examination in this period, the most constant symptoms are general asthenia, anorexia, enlargement, compaction and soreness of the liver, as well as darkening of urine and often discoloration of feces.

Frequency of symptoms in the initial period of acute hepatitis B

Symptom	Frequency, %
	Children of the first year of life	Children over 1 year old	Adults
Sharp start	57.6	34.5	15
Gradual start	42.4	65.5	85
Lethargy, weakness, increased fatigue, adynamia	42.4	61.5	100
Muscle and joint pain	-	1.3	18
Temperature increase	52.2	39.8	82
Decreased appetite, anorexia	63.9	58.4	90
Nausea, regurgitation	14	18.9	45
Vomit	37.4	34.1	32
Stomach ache		44.0	55
Catarrhal phenomena	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 with symptoms of general infectious toxicosis (lethargy, weakness, adynamia, anorexia, etc.). Half of the patients have an increase in body temperature, but, as a rule, not to high values, only in some 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. Common symptoms of the initial period of hepatitis B include dyspeptic phenomena: decreased appetite, up to anorexia, aversion to food, nausea, vomiting. These symptoms of hepatitis B usually appear from the first days of the disease and are detected throughout the initial (pre-icteric) period.

Muscle and joint pains often appear in adult patients, in children they are very rare in the pre-icteric period. Among the observed sick children, pains in the eyes were noted only in 1.3% of cases. Half of them complained of abdominal pains, which were often localized in the epigastric region, less often in the right hypochondrium or were diffuse.

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

Catarrhal symptoms are not typical for hepatitis B at all; among the patients we observed, they were observed in 15% of cases, manifested by cough, mucous discharge from the nose, and diffuse hyperemia of the mucous membrane of the oropharynx. In all these patients, catarrhal symptoms are not associated with hepatitis B, since in most cases, one can assume the addition of ARVI or mixed infection from the first days of the disease.

The most objective symptom in the initial period is enlargement, hardening and tenderness of the liver. We observed this symptom in all patients in cases where we were able to trace the development of clinical symptoms from the first day of the disease. Enlargement of the liver usually begins on the 2nd or 3rd day from the onset of the disease, tenderness is revealed somewhat earlier when palpating the right hypochondrium, sometimes even without connection with the enlargement of the liver. We observed enlargement of the spleen only in isolated patients immediately before the appearance of jaundice.

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

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

The duration of the initial (pre-icteric) period can vary widely - from several hours to 2-3 weeks; in observations it averaged 5 days. The maximum duration of the pre-icteric period in the observed patients was 11 days, but in 9.9% of patients the pre-icteric period was completely absent, and the disease in these cases began immediately with the appearance of jaundice.

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

1-2 days before the onset of jaundice, all patients experience darkening of urine and most have discolored feces. Unlike hepatitis A, with hepatitis B, the transition of the disease 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 the onset of jaundice, the symptoms of intoxication increase. In 33% of patients, subfebrile body temperature is observed on the first day of the icteric period, in 25% - nausea, vomiting, 9.3% of patients complain of abdominal pain, complete anorexia. Patients remain lethargic, complain of general weakness, poor appetite, bitter taste, bad breath, a feeling of heaviness or pain in the right hypochondrium, epigastrium or without a specific localization.

Jaundice in hepatitis B increases gradually - usually within 5-6 days, sometimes up to 2 weeks or longer. The jaundice color can vary from light yellow, canary or lemon to greenish-yellow or ocher-yellow, saffron. The degree of jaundice and its shade are associated with the severity of the disease and the development of cholestasis syndrome. Having reached its peak, jaundice in hepatitis B usually stabilizes within 5-10 days, and only after that does it begin to decrease.

Frequency of icteric period symptoms 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
Vomit	41.6	5.4	25
Stomach ache	0	11	55
Hemorrhagic rash	26.7	18.2	20
Skin rashes	-	7.8	2
Diarrhea	0	0	15
Enlargement of the liver	100,0	95	98
Enlargement of the spleen	96.3	49.3	15

As can be seen from the presented data, in the icteric period, symptoms of asthenovegetative and dyspeptic nature predominate in almost all patients. The degree of their expression 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 in children of such symptoms characteristic of hepatitis B in adults as muscle and joint pain, diarrhea, catarrhal phenomena, and itching of the skin is very rare.

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

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

In parallel with the increase in jaundice in hepatitis B, the liver increases in size, its edge becomes denser, and pain is noted upon palpation.

In typical cases of hepatitis B, an increase in liver size is observed in almost all patients (96.3%), and the liver increases uniformly with a predominance of damage to the left lobe.

Enlargement of the spleen is observed less frequently than that of the liver, in observations - in 96.3% of children in the first year of life and in 49.3% of older children. The spleen is often enlarged in more severe cases and during a long course of the disease. According to research data, in mild forms the spleen is palpable in 65%, in moderate forms - in 72%, and in severe forms - in 93%. Enlargement of the spleen is noted throughout the acute period with a slow reverse dynamics, often the spleen is palpable even after the disappearance of other (except for liver enlargement) symptoms of hepatitis B, which, as a rule, indicates a protracted or chronic course of the disease.

The most characteristic changes in the cardiovascular system in hepatitis B are bradycardia, vagal respiratory arrhythmia, decreased blood pressure, weakening of tones, impurity of the first tone or a slight systolic murmur at the apex, a slight accentuation of the second tone in the pulmonary artery, and sometimes short-term extrasystole.

In the initial period of the disease, cardiac activity is accelerated. In the icteric period, bradycardia with arrhythmia occurs. With the disappearance of jaundice, the pulse rate gradually approaches the norm, remaining labile for some time. A sudden change from bradycardia to tachycardia at the height of jaundice should be regarded as an unfavorable symptom indicating the danger of developing hepatic coma.

Cardiovascular changes in hepatitis B almost never play a serious role in the course and outcome of the disease. In the vast majority of cases, cardiac activity is normalized by the time the patient is discharged.

Electrocardiographic changes in hepatitis B in the form of thickening and reduction of the T wave, slight widening of the QRS complex, reduction of the ST interval, sinus respiratory arrhythmia are interpreted as manifestations of functional disorders of cardiac activity, and not as an indicator of myocardial damage. In fact, these changes can be considered a manifestation of "infectious heart", which is very often observed in other infectious diseases. At the same time, more pronounced electrocardiographic changes, sometimes detected in severe forms of hepatitis B, can be the result of direct toxic effects on the heart muscle, as well as a reflection of metabolic disorders in the body and the heart muscle.

Changes in the nervous system occupy a prominent place in the clinical picture of hepatitis B, they are more noticeable and vivid, the more severe the liver damage. However, even in mild cases, already at the beginning of the disease, some general depression of the central nervous system can be detected, expressed in a change in the mood of patients, decreased activity, lethargy and adynamia, sleep disturbance and other manifestations.

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

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

The number of leukocytes in the icteric period is normal or decreased. In the blood formula at the height of toxicosis, a tendency to neutrophilia is revealed, and during the recovery period - to lymphocytosis. Monocytosis is observed in a third of patients. In severe cases, moderate leukocytosis with a band shift is especially common, while ESR almost always decreases, while in mild forms, ESR is usually within normal limits. Low ESR (1-2 mm / h) with severe intoxication in a patient with a severe form of hepatitis B is an unfavorable sign.

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

Increased activity of hepatocellular enzymes in the icteric period is observed in all patients. 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 by the end of the 6-8th week of the disease and not in all patients.

In most patients, the amount of total protein in the blood serum decreases due to decreased synthesis of albumins; in some cases, the content of a1-, a2-globulins increases, and in most cases, the content of y-globulins increases, but still, pronounced dysproteinemia at the height of the disease is observed only in severe and malignant forms of the disease.

Thymol test results in hepatitis B are often normal or slightly elevated.

The indicators of the sublimate test in hepatitis B tend to decrease; a significant decrease is observed only in severe and especially malignant forms and liver cirrhosis.

Beta-lipoprotein levels in the acute period of the disease increase by 2-3 times or more, and gradually decrease to normal as the patient recovers and other biochemical tests normalize. With the development of massive liver necrosis, the beta-lipoprotein level decreases sharply, which is a poor prognostic sign.

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

During the icteric period, HBsAg, HBeAg, anti-HBC IgM continue to be detected in the blood, and in some patients antibodies to the bovine antigen of the IgG class and anti-HBV appear. Of other immunological shifts at the height of clinical manifestations, a certain decrease in T-lymphocytes is consistently detected, especially T-helper lymphocytes, with a relatively normal content of T-suppressor lymphocytes, increased sensitization of T-lymphocytes to HBsAg and hepatic lipoprotein, the content of B-lymphocytes tends to increase, the content of immunoglobulins IgM and IgG increases.

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

Incubation period of hepatitis B

The incubation period for hepatitis B is 60-180 days, most often 2-4 months, in rare cases it is reduced to 30-45 days or increases to 225 days. The duration of the incubation period depends on the infective dose and possibly age. In case of massive infection, which is usually observed during 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 household infection, the duration of the incubation period is often 6 months. In children of the first months of life, the duration of the incubation period is usually shorter (2.8 ± 1.6 days) than in children of older age groups (117.8 ± 2.6, p < 0.05).

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

Signs of hepatitis B in the convalescent (recovery) period

The total duration of the icteric period in hepatitis B varies widely - from 7-10 days to 1.5-2 months. In observations, the icteric period averaged 29.5±12.5 days, including 20.6±9.6 days in mild forms, 31.4±13 days in moderate forms, and 37.6±16 days in severe forms.

With the disappearance of jaundice, patients no longer complain, they are active, their appetite is restored, but in half of the cases hepatomegaly still remains, and in 2/3 - minor hyperfermentemia. Thymol test values, dysproteinemia phenomena, etc. may remain elevated. It should be emphasized that even within the framework of a favorable course, cases with an accelerated rate of functional recovery of the liver are possible, when the complete disappearance of clinical symptoms and normalization of functional liver tests occur after 3-4 weeks, and vice versa, there are cases when normalization of the clinical picture and biochemical changes does not occur after 4-6 months.

Studying the rate of functional recovery of the liver in 243 patients with acute hepatitis B using 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 is detected (on average 25% per day), in 48.1 - a normal rate within the confidence intervals of the universal curve (on average 13% per day), in 41.7 - a slow rate with a recovery rate of 7.5% per day, in 4% the rate of functional recovery will be 3.3% per day, which we classified as a protracted course of hepatitis B.

The dynamics of clinical recovery correlated with the rate of functional liver recovery. With its accelerated rate, no slowdown in clinical recovery was observed, with a normal rate - it was noted in 18.8% of children under one year of age and in 10.3% of older children, and with a slow rate - in 57.4 and 40.6%, respectively.

Particularly pronounced deviations in the dynamics of clinical recovery were noted in patients with a protracted course of hepatitis B.

It is important to note that the slowdown in 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, while in older children - due to the torpid course of jaundice. In some cases, the slowdown in 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, while in older children they usually manifested themselves as an increase in the activity of hepatocellular enzymes.

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

The course of hepatitis B

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

Acute course of hepatitis B

Acute hepatitis B is observed in 90% of patients. In these cases, the acute phase of the disease ends by the 25th-30th day from the onset of the disease, and in 30% of cases, by this period, complete recovery can be stated. The remaining patients have a slight increase in liver size (no more than 2 cm below the edge of the costal arch) in combination with hyperenzymemia, exceeding 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 minor hyperenzymemia; the rest have an enlarged liver in combination with dysproteinemia.

In the 3rd-4th month from the onset of the disease, complete recovery is already noted in 63%, and in the 6th month - in 93% of cases. The remaining patients have a slight increase in the size of the liver, sometimes they continue to complain of decreased appetite, intermittent abdominal pain, usually associated with food intake or physical activity. At the same time, the activity of liver-cell enzymes and other biochemical indicators remain normal.

During a detailed examination of these patients in a gastrocenter, a third of them had slight hepatomegaly that could be interpreted as an individual constitutional feature not associated with previous hepatitis B; in all the others, various gastroduodenal and hepatobiliary pathologies were documented. Most often, these patients were diagnosed with biliary dyskinesia in combination with gallbladder deformation, cholecystocholangitis, gastroduodenitis or cholecystitis, but often these patients suffered from chronic gastroduodenitis, chronic enterocolitis, etc.

Retrospective analysis of anamnestic data showed that 30% of children referred to the gastrocenter had subjective complaints (nausea, loss of appetite, belching, etc.) before contracting hepatitis B. The duration of these complaints ranged from 1 to 7 years. Half of the children had no complaints before contracting hepatitis B, but a thorough anamnesis revealed that they had either an aggravated heredity, or polyvalent allergies (food, drugs), or previous infectious diseases (intestinal infections, mumps, etc.).

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

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Prolonged course of hepatitis B

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

In the case of a protracted course, it is customary to distinguish three variants of the disease:

• Manifest protracted hepatitis is characterized by prolonged clinical and biochemical manifestations of the acute period: jaundice, hepatomegaly, hyperfermentemia, etc. (“getting stuck” in the middle of the disease).
• Persistent protracted hepatitis is accompanied by prolonged clinical and biochemical manifestations of the disease, characteristic of the period of its regression ("getting stuck" in the regression stage). 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-like protracted hepatitis is manifested by repeated exacerbations, occurring with a clinical picture, or only an increase in enzyme activity.

In the observed patients with protracted hepatitis B, complete clinical and laboratory recovery with 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. The development of chronic hepatitis B as an outcome of manifest forms of hepatitis B was not observed in any case.

Hepatitis B classification

Hepatitis B is classified in the same way as hepatitis A, by type, severity and course.

However, in the “severity form” group, along with mild, moderate and severe, they also include a malignant form, which occurs almost exclusively with hepatitis B and D, and in the “course” group, in addition to acute and protracted, they add a chronic course.

Clinical and laboratory criteria for distinguishing anicteric, latent, subclinical forms, as well as mild, moderate and severe forms of hepatitis B are fundamentally no different from those for hepatitis A.

• Clinical forms: icteric, anicteric, subclinical (inapparent) variants.
• By duration and cyclicity of the flow.
  • Acute (up to 3 months).
  • Prolonged (more than 3 months).
  • With relapses, exacerbations (clinical, enzymatic).
• Forms by severity.
  • Light.
  • Medium-heavy.
  • Heavy.
  • Fulminant (lightning).
• Complications: acute and subacute liver dystrophy with the development of hepatic encephalopathy and hepatic coma.
• Outcomes.
  • Acute hepatitis B, recovery, chronic hepatitis B, fatal outcome with the development of liver dystrophy.
  • Chronic hepatitis B: recovery (spontaneous seroconversion of HBsAg/anti-HBs), inactive carriage, liver cirrhosis, hepatocellular carcinoma.

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