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Chronic hepatitis B: symptoms
Last reviewed: 04.07.2025
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Chronic hepatitis B is found predominantly in men.
Ethnicity (countries with high carrier rates), sexual contact with infected persons, work involving contact with human blood, history of organ and tissue transplantation or immunosuppressive therapy, homosexuality and drug addiction indicate a possible connection with HBV. The probability of developing chronic infection in a child born to an HBeAg-positive mother is 80-90%. In healthy adults, the risk of chronicity after acute hepatitis is very low (about 5%). It is possible that any of the above risk factors are absent in the anamnesis.
Chronic hepatitis B may be a continuation of unresolved acute hepatitis B. The acute attack is usually mild. A patient with a dramatic onset of the disease and marked jaundice usually makes a full recovery. In patients with fulminant hepatitis who survive, progression of the disease is rare or not observed at all.
Following an acute attack, serum transaminase activity "fluctuates" against the background of intermittent jaundice. Complaints may be virtually absent, and patients may only have biochemical signs of an active process or may complain of weakness and malaise; in this case, the diagnosis is established after a routine examination.
Chronic hepatitis B can be diagnosed in donors during blood donation or routine blood screening based on the detection of HBsAg and moderate elevations in serum transaminase activity.
Chronic hepatitis is often a "silent" disease. Symptoms do not correlate with the severity of liver damage.
Approximately half of patients present with jaundice, ascites, or portal hypertension, which indicate an advanced process. Encephalopathy is uncommon at presentation. The patient is usually unable to indicate a previous acute attack of hepatitis. Some patients present with hepatocellular carcinoma.
Clinical signs of exacerbation and reactivation of the virus
Patients with a fairly stable course of chronic hepatitis B may develop clinical signs of exacerbation. This is expressed in worsening weakness and usually in an increase in the activity of serum transaminases.
Exacerbation may be associated with seroconversion from HBeAg-positive to HBeAg-negative status. Liver biopsy reveals acute lobular hepatitis, which eventually subsides, and serum transaminase activity falls. Seroconversion may be spontaneous and occurs annually in 10-15% of patients, or is a consequence of antiviral therapy. The HBV DNA test may remain positive even when anti-HBe appears. In some HBeAg-positive patients, "flares" of viral replication and increases in serum transaminase activity occur without the disappearance of HBeAg.
Spontaneous reactivation of the virus with transition from HBeAg-negative to HBeAg- and HBV-DNA-positive state has also been described. The clinical picture varies from minimal manifestations to fulminant liver failure.
Viral reactivation is particularly difficult for HIV-infected patients.
Reactivation can be determined serologically by the appearance of anti-HBc IgM in the blood.
Reactivation may result from cancer chemotherapy, low-dose methotrexate for rheumatoid arthritis, organ transplantation, or administration of corticosteroids to HBeAg-positive patients.
Severe disorders are associated with mutations in the pre-core region of the virus, when the e-antigen is absent in the presence of HBV DNA.
Superinfection with HDV is possible. This leads to a significant acceleration of the progression of chronic hepatitis.
Superinfection with HAV and HCV is also possible.
As a result, any deviations in the course of the disease in HBV carriers increase the possibility of developing hepatocellular carcinoma.
Chronic hepatitis B associated with the replication phase (HBeAg-positive replicative chronic hepatitis B)
Clinical and laboratory data in this variant of chronic hepatitis B are consistent with active hepatitis.
Patients complain of general weakness, fatigue, elevated body temperature (up to 37.5°C), weight loss, irritability, poor appetite, a feeling of heaviness and pain in the right hypochondrium after eating, a feeling of bitterness in the mouth, bloating, and unstable stool. The higher the activity of the pathological process, the more pronounced the subjective manifestations of the disease.
When examining patients, attention is drawn to transient yellowness of the skin and sclera (not often), weight loss, and with high activity of chronic hepatitis, hemorrhagic phenomena are possible (nosebleeds, hemorrhagic rashes on the skin). The appearance of "spider veins" on the skin, skin itching, "liver palms", and transit ascites usually indicate transformation into liver cirrhosis, but these same symptoms can also be observed with pronounced activity of chronic hepatitis.
Objective examinations reveal hepatomegaly of varying degrees of severity in all patients. The liver is painful, of a dense-elastic consistency, its edge is rounded. An enlarged spleen may be palpated, but the degree of its enlargement is often insignificant. Expressed hepatosplenomegaly with hypersplenism is more characteristic of liver cirrhosis.
In some cases, a cholestatic variant of chronic hepatitis B may be observed. It is characterized by jaundice, skin itching, hyperbilirubinemia, hypercholesterolemia, high blood levels of y-glutamyl transpeptidase and alkaline phosphatase.
In a small number of patients with chronic hepatitis B, extrahepatic systemic lesions are detected with involvement in the inflammatory process of the digestive organs (pancreatitis), exocrine glands (Sjogren's syndrome), thyroid gland (Hashimoto's autoimmune thyroiditis), joints (polyarthralgia, synovitis), lungs (fibrosing alveolitis), muscles (polymyositis, polymyalgia), blood vessels (nodular periarteritis and other vasculitis), peripheral nervous system (polyneuropathy), kidneys (glomerulonephritis).
However, it should be emphasized that pronounced extrasystemic lesions are much more characteristic of autoimmune hepatitis and the transformation of chronic hepatitis into liver cirrhosis.
[ 10 ], [ 11 ], [ 12 ], [ 13 ], [ 14 ], [ 15 ], [ 16 ]
Chronic hepatitis B associated with the integrative phase (HBeAg-negative integrative chronic hepatitis B)
HBeAg-negative integrative chronic hepatitis B has a favorable course. As a rule, this is the inactive phase of the disease. This variant of chronic hepatitis usually proceeds without pronounced subjective manifestations. Only some patients complain of mild weakness, loss of appetite, mild pain in the liver. An objective examination of patients does not reveal any significant changes in their condition (no jaundice, weight loss, lymphadenopathy, or systemic extrahepatic manifestations). However, hepatomegaly is almost always present and very rarely, minor splenomegaly. As a rule, the spleen is not enlarged. Laboratory parameters are usually normal or at the upper limit of normal, the level of alanine aminotransferase is not increased or is slightly increased, there are no significant changes in immunological parameters.
Liver biopsies reveal lymphocytic-macrophage infiltration of the portal fields, intralobular and portal fibrosis, and no hepatocyte necrosis.
Markers of the hepatitis virus integration phase are detected in the blood serum: HBsAg, anti-HBe, anti-HBdgG.
Radioisotope and ultrasound scanning of the liver reveal hepatomegaly of varying degrees of severity.
Chronic HBeAg-negative (integrative) hepatitis with high levels of alanine aminotransferase in the blood - integrative mixed hepatitis
In this variant of HBeAg-negative (integrative) chronic hepatitis, despite the absence of markers of hepatitis B virus replication, high levels of alanine aminotransferase in the blood are maintained, indicating ongoing pronounced cytolysis of hepatocytes. It is generally accepted that the maintenance of a high level of alanine aminotransferase in the absence of signs of virus replication requires the exclusion of the addition of other hepatotropic viruses (integrative mixed hepatitis B + C, B + D, B + A, etc.) or may indicate a combination of viral hepatitis B in the integration phase with other liver diseases (alcoholic, drug-induced liver damage, liver cancer, etc.).
[ 20 ], [ 21 ], [ 22 ], [ 23 ], [ 24 ], [ 25 ], [ 26 ], [ 27 ]
HBeAg-negative hepatitis with preserved viral replication (mutant HBeAg-negative variant of chronic hepatitis B)
In recent years, the ability of the hepatitis B virus to produce mutant strains has been described. They differ from typical "wild" strains by the lack of ability to produce specific antigens. Mutations of the hepatitis B virus are caused by an incomplete weakened response of the body to the infection, as well as the introduction of vaccinations against hepatitis B. The cessation of antigen synthesis is considered as an adaptation of the virus to the mechanisms of protection of the macroorganism, as an attempt to escape from immunological surveillance.
The mutant HBeAg-negative variant of chronic hepatitis B is characterized by the loss of the ability of the virus to synthesize HBeAg and occurs mainly in patients with a weakened immune response.
The mutant HBeAg-negative variant of chronic hepatitis B is characterized by the following features:
- absence of HBeAg in the blood serum (due to low production, it remains in hepatitis) in the presence of HBV replication markers;
- detection of HBV DNA in the blood serum of patients;
- the presence of HBeAb in the blood serum;
- the presence of HBS antigenemia in high concentrations;
- detection of HBeAg in hepatocytes;
- more severe clinical course of the disease and a much less pronounced response to interferon treatment compared to HBeAg-positive chronic hepatitis B.
F. Bonito, M. Brunetto (1993), Nonaka et al. (1992) report a severe, clinically manifested course of mugative HBeAg-negative chronic hepatitis B. The morphological picture of liver biopsies corresponds to HBeAg-positive chronic hepatitis B, and the development of destructive liver damage of the chronic active hepatitis type is possible.
It is assumed that in mutant HBeAg-negative chronic hepatitis there is a high risk of malignancy with the development of hepatocarcinoma.