Taxonomy and morphology
The causative agent belongs to the family Hepadnaviridae, genus Orthohepadnavirus, species hepatitis B virus. It is a reverse-transcribing DNA-containing virus with a complex spherical virion.
The virion structure includes the following components:
- Core (nucleocapsid) — composed of 180 protein subunits representing the HBc antigen;
- Lipoprotein envelope, containing the surface HBs antigen, formed by three glycosylated polypeptides (preS1, preS2, S);
- Inside the core are genomic DNA, viral DNA polymerase, and the HBe antigen.
The genome is represented by a double-stranded circular DNA, with genetic information encoded on the minus strand and containing four transcripton genes. Replication requires the completion of the plus strand, which serves as a template for the synthesis of mRNA and proteins.
Antigenic structure
Viral antigens form the basis of serological diagnosis:
- HBs antigen — surface antigen, detected in the blood both as part of virions and as standalone subviral particles;
- HBc antigen — core antigen, detected only in infected hepatocytes (liver biopsy), not circulating in free form in the blood;
- HBe antigen — associated with active viral replication in hepatocytes, detected in the blood;
- HBx antigen — transactivator, its accumulation is associated with the development of primary hepatocellular carcinoma.
Life cycle and pathogenesis
The virus exhibits a marked tropism for hepatocytes, which is determined by the presence of specific receptors on their membrane and the presence in these cells of transcription factors required for viral mRNA synthesis.
Following endocytosis, the supercapsid is degraded, the nucleocapsid enters the cell, and the viral DNA enters the nucleus. The virion DNA polymerase completes the plus strand, forming a closed circular double-stranded DNA — the template for transcription. After mRNA synthesis in the cytoplasm, translation of viral proteins, assembly of new nucleocapsids, and formation of virions take place.
Two forms of the infectious process are distinguished:
- Integrative — viral DNA is integrated into the hepatocyte genome; characterized by the synthesis of HBs antigen, which corresponds to virus carrier state;
- Productive — complete virions are formed; acute or chronic hepatitis develops, with IgM class antibodies to the HBc antigen serving as a marker.
Epidemiology and immunity
Hepatitis B is an anthroponosis; the source of infection is a sick person or a virus carrier. The entry portal consists of microtraumas of the skin and mucous membranes.
Routes of transmission: parenteral, hemocontact, sexual, vertical (transplacental and during passage through the birth canal). The incubation period is 3–6 months.
Rule of threes: the risk of infection from an infected needle stick is 30% for hepatitis B, 3% for hepatitis C, and 0.3% for HIV infection.
Immunity is both humoral and cellular. Humoral immunity is represented by antibodies to the HBs antigen, which eliminate the virus from the blood. Cellular immunity is mediated by cytotoxic T lymphocytes, which recognize the HBc antigen and destroy infected hepatocytes.
Clinical presentation and laboratory diagnostics
The clinical picture includes asthenovegetative syndrome (fatigue, irritability, sleep disturbances), dyspeptic disorders, myalgia, arthralgia, heaviness and dull pain in the right upper quadrant. An asymptomatic course is possible.
Test material: blood, saliva, urine, semen, vaginal secretions, synovial and cerebrospinal fluids, breast milk. Virological methods are rarely used because the virus only cultures in primary hepatocellular carcinoma cell lines without a pronounced cytopathic effect. The main methods are PCR and serological studies (ELISA).
Diagnostic markers:
- HBV DNA — presence and replication of the virus;
- HBs antigen — fact of infection;
- HBe antigen — active replication, high blood infectivity, risk of perinatal transmission;
- HBc antigen — detected only in liver biopsies;
- anti-HBc IgM — early marker of acute infection or exacerbation of chronic infection;
- anti-HBe — onset of convalescence;
- anti-HBs — past infection or post-vaccination immunity.
Prevention and treatment principles
Nonspecific prevention includes compliance with asepsis and antisepsis rules, control of blood products, and parenteral procedures.
Specific prevention:
- Active — vaccination with a recombinant genetically engineered vaccine containing the HBs antigen;
- Passive — administration of specific hepatitis B immunoglobulin upon potential exposure to the pathogen (e.g., after an accidental needle stick with an infected needle).
The goals of etiotropic therapy are to reduce viral load and prevent cirrhosis and hepatocellular carcinoma. Pegylated interferon alfa (in the absence of cirrhosis, presence of HBe antigen, in treatment-naive patients) and nucleoside/nucleotide analogues are used: lamivudine, entecavir (for lamivudine resistance), tenofovir (acceptable when planning pregnancy).
Key points
- Hepatitis B virus is a complex DNA-containing virus of the family Hepadnaviridae with reverse transcription.
- HBs, HBc, and HBe antigens have different localizations and form the basis of serodiagnosis.
- Tropism for hepatocytes is provided by specific receptors and hepatic transcription factors.
- Infection occurs in an integrative (carrier state) or productive (hepatitis) form.
- Transmission is parenteral, sexual, vertical; the risk from an infected needle stick is 30%.
- A key early marker of acute infection is anti-HBc IgM; a marker of vaccine immunity is anti-HBs.
- Specific prevention is based on a recombinant vaccine with the HBs antigen.
- Etiotropic therapy includes peginterferon alfa and nucleoside analogues (lamivudine, entecavir, tenofovir).