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Hepatitis A - Causes and Pathogenesis
Last reviewed: 06.07.2025
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The causative agent of viral hepatitis A is the HAV virus (hepatitis A virus), belonging to the genus Hepatovirus in the family Picornaviridae. Morphologically, HAV looks like a small, non-enveloped spherical particle measuring 27-30 nm. The genome is represented by a single-stranded RNA molecule consisting of approximately 7500 nucleotides. The RNA of the virus is surrounded by an outer protein capsule (capsid). Only one HAV antigen is known - HAAg, to which the macroorganism produces antibodies. When studying numerous HAV strains isolated from patients in different regions of the world and from experimentally infected monkeys, the presence of 7 genotypes and several subtypes of HAV was established. The strains isolated in Russia belong to the IA variant of the virus. All known HAV isolates belong to one serotype, which ensures the development of cross-protective immunity. HAV is hepatotropic and has a weak cytopathogenic effect on liver cells. HAV is one of the most resistant human viruses to environmental factors. It can survive at room temperature for several weeks, at +4 °C for months, and at -20 °C it remains viable for several years. It can withstand heating to 60 °C for 4-12 hours; it is resistant to acids and fat solvents, and can be preserved for a long time in water, food products, wastewater, and on various environmental objects. It is destroyed within 5 minutes when boiled and within 15 minutes when treated with chloramine. The virus is sensitive to formalin and ultraviolet radiation. It is also inactivated by autoclaving. potassium permanganate, iodine compounds, 70% ethanol, and disinfectants based on quaternary ammonium compounds.
[ Pathogenesis of hepatitis A
HAV enters the body through the mouth and then into the stomach. Being acid-resistant, 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 occurs. On the membrane of hepatocytes there are receptors corresponding to the virus, to which HAV attaches and penetrates into the liver cell; its replication occurs in the cytoplasm of the hepatocyte. Some of the newly formed viral particles enter the feces with bile and are excreted from the body, others infect neighboring hepatocytes.
It has been established that long-term replication of HAV in cell culture is not accompanied by cytolysis of hepatocytes. Therefore, it is currently believed that liver damage in viral hepatitis A is caused not so much by HAV itself as by human cellular immune reactions. Cytotoxic T cells recognize and lyse virus-infected hepatocytes. In addition, these same T lymphocytes produce gamma interferon, triggering a number of immune reactions. Liberation from the virus occurs largely due to immunologically mediated destruction of liver cells. Due to the disintegration of necrotic hepatocytes, the virus and its "fragments" enter the blood, i.e., a secondary viremia phase occurs.
HAV has high immunogenic activity. Simultaneously with the cellular component, the humoral component of the immune system is also activated with the accumulation of virus-neutralizing antibodies. Due to the rapid and intense immune response, virus replication is blocked, and its further penetration into uninfected hepatocytes is limited. As a result of the combined action of all links of the immune system, as a rule, the body is freed from HAV within a few weeks, therefore, with viral hepatitis A, there is neither long-term virus carriage nor chronic forms. The adequacy of the protective immune response in viral hepatitis A explains its relatively mild course, the exceptional rarity of fulminant forms with a fatal outcome, and complete recovery in the overwhelming majority of cases. Massive necrosis of hepatocytes usually does not occur in viral hepatitis A. The bulk of hepatocytes remains intact. As with other acute viral hepatitis, with viral hepatitis A, acute diffuse inflammation of the liver occurs, which can be detected even before the appearance of jaundice. In viral hepatitis A, the liver is the only target organ in which viral replication occurs, so extrahepatic manifestations of viral hepatitis A are not typical.
HLA molecules participate in the lysis of hepatocytes affected by HAV. As a result, autoimmune mechanisms are "triggered" during the course of the disease with the formation of antibodies to one's own hepatocytes. In individuals with a genetic predisposition to autoimmune reactions, HAV can initiate the development of autoimmune hepatitis type 1. Current data on the pathogenesis of viral hepatitis A allow this disease to be interpreted as acute, benign, and self-limiting, although in 1996 Japanese authors published the first report of chronic viral hepatitis A and persistent viral replication in humans.