Hepatitis A: causes and pathogenesis
Last reviewed: 23.04.2024
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The causative agent of viral hepatitis A is the virus HAV (hepatitis A virus), attributed to the genus Hepatovirus in the family Picornaviridae. Morphologically, the HAV looks like a shallow, non-shell spherical particle measuring 27-30 nm in size. The genome is represented by a single-stranded RNA molecule consisting of approximately 7,500 nucleotides. RNA of the virus is surrounded by an outer protein capsule (capsid). Only one HAV-HAAg antigen is known. On which the macroorganism produces antibodies. In the study of numerous strains of HAV isolated from patients in different regions of the world and from experimentally infected monkeys, seven genotypes and several subtypes of HAV have been identified. The strains isolated in Russia belong to the version of the virus IA. All known HAV isolates are classified as a single serotype, which ensures the development of cross-protective immunity. HAV - hepatotropic, has a weak cytopathic effect on liver cells. HAV is considered one of the most resistant to environmental factors of human viruses. It has the ability to be stored at room temperature for several weeks, at +4 ° C for months, at -20 ° C it remains viable for several years. Withstands heating to 60 ° C for 4-12 hours; resistant to the action of acids and fat solvents, is capable of long-term preservation in water, food products, sewage, at various objects of the external environment. When boiled, it breaks down for 5 minutes, when treated with chloramine - after 15 minutes. The virus is sensitive to formalin}, ultraviolet irradiation. It is also inactivated by autoclaving. Potassium permanganate, iodide compounds, 70% ethanol, disinfectants based on quaternary ammonium compounds.
[The pathogenesis of hepatitis A
The introduction of HAV into the body occurs through the mouth and then into the stomach. Being acid-fast, the virus easily overcomes the gastric barrier, enters the small intestine, is absorbed into the blood and reaches the liver through the portal vein system. In the cells of which its replication takes place. On the membrane of hepatocytes there are viruses corresponding to the virus, to which HAV is attached and penetrates into the hepatic cell; In the cytoplasm of the hepatocyte, its replication takes place. Part of newly formed viral particles comes with bile in feces and is excreted from the body, the other infects nearby hepatocytes.
It has been established that prolonged replication of HAV in cell culture does not accompany cytolysis of hepatocytes. Therefore, it is now believed that liver damage in viral hepatitis A is due not so much to HAV itself, but to the cellular immune responses of a person. Cytotoxic T cells recognize and lyse virus-infected hepatocytes. In addition, these same T-lymphocytes produce gamma-interferon, triggering a number of immune responses. Exemption from the virus occurs largely due to immunologically mediated destruction of the hepatic cells. Due to the breakdown of hepatocytes that have undergone necrosis, the virus and its "fragments" enter the blood, that is, a phase of secondary viremia occurs.
HAV has a high immunogenic activity. Simultaneously with the cellular, activation of the humoral component of the immune system takes place with the accumulation of virus neutralizing antibodies. Due to a rapid and intensive immune response, a blockage of viral replication occurs, and its further introduction into uninfected hepatocytes is limited. As a result of the combined action of all parts of the immune system, as a rule, after a few weeks the body is released from HAV, so for viral hepatitis A there is neither a long-term virus carrier nor chronic forms. The adequacy of the protective immune response in viral hepatitis A is attributed to its relatively easy course, the exceptional rarity of fulminant forms with a lethal outcome, complete recovery in the vast majority of cases. Massive necrosis of hepatocytes in viral hepatitis A usually does not happen. The bulk of hepatocytes remains intact. As with other acute viral hepatitis, with viral hepatitis A there is acute diffuse inflammation of the liver, which can be detected even before the appearance of jaundice. With viral hepatitis A, the liver is the only target organ in which the virus replicates; therefore, extrahepatic manifestations of viral hepatitis A are not inherent.
HLA molecules are involved in the lysis of HAV infected hepatocytes. As a result of which "autoimmune mechanisms" are triggered during the course of the disease, with the formation of antibodies to their own hepatocytes. In individuals with a genetic predisposition to autoimmune reactions, HAV can initiate the development of autoimmune hepatitis of the first type. Current data on the pathogenesis of viral hepatitis A can treat this disease as acute, benign with the ability to self-limiting, although in 1996 Japanese authors published the first report on chronic viral hepatitis A and persistent viral replication in humans.