Hepatitis B: causes

Hepatitis B virus (HBV) belongs to the hepadnavirus family (hepar - liver, DNA - DNA, i.e. DNA-containing viruses that affect the liver), the genus Orthohepadnavirus. Hepatitis B virus or Dane particle has a spherical shape, 40-48 nm in diameter (42 nm on average). The membrane consists of a phospholipid bilayer 7 nm thick, into which surface antigen particles are immersed, consisting of several hundred protein molecules, glycoproteins and lipoproteins. Inside HBV there is a nucleocapsid or core, which has the shape of an icosahedron 28 nm in diameter, containing the HBV genome, terminal protein and the enzyme DNA polymerase. The HBV genome is represented by a partially double-stranded DNA molecule, which has an open ring shape and contains about 3200 nucleotide base pairs (3020-3200). HBV DNA includes four genes: S-gene, encoding the surface antigen of the envelope - HBsAg; C-gene, encoding HBcAg; P-gene, encoding information about the enzyme DNA polymerase, which has the function of reverse transcriptase; X-gene, carrying information about the X-protein.

HBsAg is synthesized in the cytoplasm of the hepatocyte. During viral replication, a significant excess of HBsAg is formed, and thus, HBsAg particles predominate in the patient's blood serum, rather than full-fledged viruses - on average, there are from 1000 to 1,000,000 spherical HBsAg particles per viral particle. In addition, the blood serum of patients with viral hepatitis B may contain defective virions (up to 50% of the entire pool circulating in the blood), the nucleocapsid of which does not contain HBV DNA. It has been established that there are 4 main subtypes of HBsAg: adw, adr, ayw, ayr. In Ukraine, mainly the ayw and adw subtypes are registered. Based on the analysis of the nucleotide sequences of the S and Pre-S gene, virus isolates obtained in different regions of the world are grouped into 8 main genotypes, which are designated by letters of the Latin alphabet: A, B, C, D, E, F, G and H. Genotype D prevails in Ukraine, while genotype A is registered less frequently. A complete correspondence between HBV genotypes and HBsAg serotypes has not been established. The study of HBV subtypes and genotypes is important for establishing the relationship between a certain virus variant and the severity of acute and chronic hepatitis, the development of fulminant viral hepatitis B, for creating vaccines and assessing the effectiveness of antiviral therapy.

The probability of developing severe hepatitis against the background of acute hepatitis B and the formation of hepatocellular carcinoma in patients with chronic hepatitis B is higher among those infected with genotype C compared to genotype B. Genotype B is more likely to undergo HBe/anti-HBe seroconversion at a young age compared to genotype C. Patients with genotypes A and B have a higher probability of responding to interferon treatment compared to patients infected with genotypes A and B.

The HBV S-gene is responsible for the synthesis of HB-Ag, which causes the production of neutralizing antibodies, so the S-gene is used to produce genetically engineered vaccines.

Gene C (core gene) codes for the nucleocapsid protein (HBcAg), which has the ability to self-assemble into core particles, into which HBV DNA is packaged after the replication cycle is completed. The core gene contains a pre-core zone encoding a pre-core polypeptide that is modified into a soluble form and secreted into the endoplasmic reticulum and then into the blood as the protein HBeAg (HBV e-antigen). HBeAg is one of the main epitopes that causes the formation of a pool of specific cytotoxic T lymphocytes, which migrate to the liver and are responsible for the elimination of the virus. It has been established that mutations in the pre-core zone lead to a decrease or complete cessation of HBeAg production. In the development of chronic hepatitis B, the selection of HBeAg-negative HBV strains, due to their evasion of the body's immune control, leads to the transition of chronic HBeAg-positive viral hepatitis B to the stage of HBeAg-negative chronic hepatitis B. Patients with HBeAg-negative chronic hepatitis B may have a different biochemical profile of the disease (wave-like nature of the ALT level), they have a lower content of HBV DNA in the blood, and they respond worse to therapy with antiviral drugs.

The P gene encodes a protein with enzymatic activity, HBV DNA polymerase. This enzyme also functions as a reverse transcriptase. The clinical significance of mutations in the HBV DNA P gene is primarily associated with resistance to treatment with nucleoside analogues of chronic hepatitis B.

The X gene encodes a protein that plays an important role in the development of primary liver cancer in HBV carriers. In addition, the X protein is capable of activating the replication of other viruses, in particular HIV, which determines the deterioration of the clinical course in individuals infected with the HBV and HIV viruses.

Antibodies are produced against each HBV antigen in the human body. In clinical practice, detection of antigens and antibodies is used to diagnose viral hepatitis B, determine the stage of the process, prognosis, evaluate the effectiveness of therapy, determine indications for vaccination and revaccination.

HBV is highly resistant to physical and chemical factors, remains viable in blood serum at room temperature for 3 months, at 20 °C - 15 years, in dried plasma - up to 25 years, does not die under the action of many disinfectants and blood preservatives. It is inactivated by autoclaving (45 min) and sterilization with dry heat (+160 °C). It is sensitive to ether and non-ionic detergents. Aldehydes and chlorine compounds are mainly used for chemical disinfection.

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