Hepatitis D: causes and pathogenesis
Last reviewed: 23.04.2024
All iLive content is medically reviewed or fact checked to ensure as much factual accuracy as possible.
We have strict sourcing guidelines and only link to reputable media sites, academic research institutions and, whenever possible, medically peer reviewed studies. Note that the numbers in parentheses ([1], [2], etc.) are clickable links to these studies.
If you feel that any of our content is inaccurate, out-of-date, or otherwise questionable, please select it and press Ctrl + Enter.
In 1977, a group of Italian researchers in hepatocytes of patients with viral hepatitis B detected a previously unknown antigen. It was assumed that this is the 4th antigen of virus B (by analogy with the already known antigens HBs, HBc, HBe), and in connection with this it was called the 4th letter of the Greek alphabet - delta. Subsequently, the experimental infection of chimpanzees with serum containing delta antigen proved that it was a new virus. At the suggestion of WHO, the causative agent of viral hepatitis D was called hepatitis delta virus - HDV. Most researchers do not refer it to any of the known taxonomic categories, considering it the only representative of the new genus - Deltavirus. Features of HDV are due to the fact that there are no sections encoding the enveloped proteins of the virus in the delta-particle genome. This feature of HDV, along with the inability to cause infection without infection by another virus (HBV). Allowed to refer it also to the group of viroids or virusoids in the first years of studying this infectious agent.
HDV (hepatitis D virus) is a spherical particle with a diameter of about 36 nm (from 28 to 39 nm), this is the smallest of known animal viruses. It consists of a nucleocapsid (18 nm) constructed of approximately 70 subunits of delta antigen (HDAg) and HDV RNA. The outer membrane is formed by the surface antigen HBV. The outer membrane of HDV is represented by HBsAg.
There are two varieties of HDAg with a molecular weight of 24 kDa (HDAg-S) and 27 kDa (HDAg-L) with pronounced functional differences in the viability of the virus. Currently, it is believed that the small form of HDAg-S is required for HDV replication and increases the rate of replication of HDV RNA (transactivator of viral replication), while the larger one (HDAg-L) participates in the assembly of the viral particle and reduces the rate of HDV replication. In addition, HDAg-L is involved in intracellular migration of viral proteins. The delta antigen is localized in the nuclei of infected hepatocytes, in the nucleoli and, or nucleoplasm. HDAg has a pronounced RNA-binding activity. The specificity of this binding determines the absence of interaction with other viral and cellular RNAs. The HDV genome is represented by a single-stranded cyclic RNA molecule of negative polarity with a length of about 1700 nucleotides.
The interaction of HBV and HDV determines not only the formation of the outer shell of HDV by means of HB-Ag. But also, perhaps, other mechanisms that are not yet fully understood. At present, there is no doubt that HDV can inhibit HBV replication. Leading to a decrease in the expression of HBeAg and HBsAg and inhibition of DNA polymerase activity during acute infection - co-infection.
Three genotypes and several subtypes of HDV are known. Genotype I is prevalent in all regions of the world and mainly circulates in Europe. Russia, and North America. South Pacific and the Middle East. Genotype II is common on Fr. Taiwan and the Japanese islands. Genotype III is found mainly in South America and the Central African Republic. All genotypes of HDV belong to the same serotype.
HDV is resistant to high temperatures, it is not affected by acids and UV radiation. The virus can be inactivated with alkalis and proteases. Repeated freezing and thawing does not affect its activity.
[The pathogenesis of hepatitis D
Once in the body of the carrier of HBV, the delta virus finds favorable conditions for its replication, as it immediately surrounds itself with a sheath of HBs antigen and then penetrates into hepatocytes due to the presence on their surface of polymerized albumin having an affinity for HBsAg forming the outer envelope of HDV. Extra-hepatic reproduction of HDV is not established.
The delta virus has both a direct cytopathic effect and an immuno-mediated effect similar to HBV. One of the evidences of cytopathic action is a significant predominance of necrotic changes over inflammatory ones, revealed by morphological examination of liver tissue of patients with viral hepatitis D. At the same time, data on the absence of cytopathic action of HDV with pronounced immunity disorders were obtained, suggesting the presence of an immunologically mediated mechanism of hepatocyte damage.
When infected with delta virus, two variants of delta infection are possible: co-infection and superinfection. The first occurs when HDV enters the body of a healthy person simultaneously with HBV. Superinfection develops in previously infected with virus B (in patients with viral hepatitis B or carriers of HBsAg) with additional infection with their delta virus.
Hepatitis, which occurs as a result of co-infection. Is commonly referred to as acute hepatitis of a mixed etiology of HBV, HDV, or acute hepatitis B with a delta-agent, thereby emphasizing the involvement of both viruses in the pathogenesis of the disease. HDV products occur simultaneously with HBV, but. Probably, the active replication of the delta virus follows after the development of structural components of HBV (HBsAg), and its duration is limited by the duration of HBs-antigenemia. Hepatitis mixed aetiology ends after elimination from the body of both viruses. When superinfection develops acute viral hepatitis delta, which is commonly referred to as acute delta (super) -infection of the virus carrier of viral hepatitis B.
In this case, the involvement of HBV in the development of liver damage is minimal, and all emerging pathological changes and clinical manifestations are due to the action of the delta virus. Unlike coinfection, which usually has an acute self-limiting course, superinfection characterizes a severe progressive course until the onset of massive liver necrosis or the rapidly progressive development of cirrhosis. This is due to the fact. That in chronic HBV infection (in carriers of HBsAg, sick with hepatitis B virus) in the liver, HBsAg is constantly formed in large quantities, and HDV finds very favorable conditions for replication and the realization of its damaging effect. There are no specific pathomorphological signs inherent in hepatitis delta, most researchers do not detect. With coinfection, there are changes similar to those with "pure" acute hepatitis B, but the necrotic process in hepatocytes is usually more pronounced. For chronic viral hepatitis D, there are significant inflammatory and necrotic changes in lobules with pronounced periportal hepatitis, high activity of the process in the liver (chronic active hepatitis of moderate and severe activity prevails), rapid violation of liver architectonics and the possibility of the appearance of morphological signs of liver cirrhosis in the early stages of the disease from 2 to 5 years).