Hepatitis B: causes

Hepatitis B virus (HBV) belongs to the family of hepadnaviruses (hepar- liver, DNA-DNA, ie DNA-containing viruses that infect the liver), the genus Orthohepadnavirus. Hepatitis B virus or Dain particle has a spherical shape, diameter 40-48 nm (average 42 nm). The shell consists of a phospholipid bilayer 7 nm thick, in which the surface antigen particles are immersed, consisting of several hundred molecules of protein, glycoproteins and lipoproteins. Inside the HBV is nucleocapsid. Or a core , having the shape of an icosahedron 28 nm in diameter, containing the HBV gene. Terminal protein and enzyme DNA polymerase. The HBV genome is represented in part by a double-stranded DNA molecule having an open ring form and containing about 3200 nucleotide base pairs (3020-3200). HBV DNA comprises four genes: S gene encoding the surface envelope antigen HBsAg: C gene encoding HBcAg: a P gene encoding the enzyme information of a DNA polymerase having the function of reverse transcriptase; X-gene, which carries information about X-protein.

HBsAg is synthesized in the cytoplasm of the hepatocyte. During the replication of the virus, a significant excess of HBsAg is formed, and. Thus, in the blood serum of the patient, HBsAg particles predominate, rather than full-fledged viruses - an average of one to 1,000,000 HBsAg spherical particles per virus particle. In addition, in the serum of patients with viral hepatitis B there may be the presence of defective virions (up to 50% of the total pool circulating in the blood), the nucleocapsid of which does not contain HBV DNA. It is established that there are 4 main subtypes of HBsAg: adw, adr, ayw, ayr. In Ukraine, mainly subtypes ayw and adw are registered. Based on the analysis of the nucleotide sequences of the S and Pre-S genes, the isolates of the virus isolated in various regions of the world are united into 8 main genotypes, denoted by the letters of the Latin alphabet: A, B, C, D, E, F, G and N. In Ukraine prevails genotype D, rarely register genotype A. Complete correspondence between the genotypes of HBV and serotypes of HBsAg is not established. The study of subtypes and genotypes of HBV is important for establishing the connection of a specific variant of the virus with the severity of the course of acute and chronic hepatitis, the development of fulminant viral hepatitis B, for the creation of vaccines and evaluation of the effectiveness of antiviral therapy.

The likelihood 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 than genotype B. Genotype B is more characteristic of seroconversion of HBe / anti-HBe at a young age in comparison with genotype C. Patients with genotypes A and B have a higher probability of responding to interferon therapy compared to patients infected with genotypes A and B.

The S gene of HBV 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) encodes a nucleocapsid protein (HBcAg). It has the ability to self-assemble into core-particles into which the HBV DNA is packed after completion of the replication cycle. In the core gene, a pre-co-zone encoding the pr-co-polypeptide is modified, which is modified into a soluble form and secreted into the endoplasmic reticulum and then into the blood protein - HBeAg (e-antigen HBV). HBeAg is one of the main epitopes that cause the formation of a pool of specific cytotoxic T lymphocytes. Which migrate to the liver and are responsible for eliminating the virus. It was 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 strains of HBV caused by their escape from 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 the profile of the disease (undulating character of the ALT level), they have a lower HBV DNA content in the blood, they respond worse to antiviral therapy.

Gene P encodes a protein that has enzymatic activity - HBV DNA polymerase. This enzyme also performs the function of reverse transcriptase. The clinical significance of mutations in the P-gene of HBV DNA is primarily associated with resistance to treatment with analogues of chronic hepatitis B nucleosides.

Gene X codes for a protein that plays an important role in the development of primary liver cancer in HBV virus carriers. Besides. X-protein is able to activate the replication of other viruses, in particular HIV, which determines the deterioration of the clinical course in people infected with the HBV and HIV virus.

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

HBV is highly resistant to physical and chemical factors, retains viability in serum at room temperature for 3 months, at 20 ° C - 15 years, in dried plasma - up to 25 years, does not die with the action of many disinfectants and blood preservatives. It is inactivated by autoclaving (45 min) and dry heat sterilization (+160 ° C). Sensitive to ether and nonionic detergents. For chemical disinfection, use is mainly made of aldehydes and chlorine compounds.

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