Chronic HDV (hepatitis delta virus) hepatitis

Negro, Francesco; Baldi, M.; Bonino, Ferruccio; Rocca, Giuseppe; Demartini, Alberto; Passarino, G; Maran, E; Lavarini, C; Rizzetto, Mario; Verme, G

doi:10.1016/s0168-8278(88)80457-4

Cited by 61 publications

(12 citation statements)

References 17 publications

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“…Longitudinal cohort studies have shown that chronic hepatitis D induces a threefold higher risk of progression to cirrhosis as compared with patients infected by HBV only 67 . HDV replicates in hepatocytes and the pathologic changes it induces are limited to the liver, which are characterized by hepatocyte necrosis and inflammatory infiltrates that may correlate with intrahepatic replication levels 68 . Thus, since HDV RNA can persist in the liver in the absence of HBV for at least 6 weeks 69 , its propagation could be triggered upon superinfection by other hepatitis viruses such as HCV as well as other viral infections.…”

Section: Discussionmentioning

confidence: 99%

Enveloped viruses distinct from HBV induce dissemination of hepatitis D virus in vivo

et al. 2019

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Hepatitis D virus (HDV) doesn’t encode envelope proteins for packaging of its ribonucleoprotein (RNP) and typically relies on the surface glycoproteins (GPs) from hepatitis B virus (HBV) for virion assembly, envelopment and cellular transmission. HDV RNA genome can efficiently replicate in different tissues and species, raising the possibility that it evolved, and/or is still able to transmit, independently of HBV. Here we show that alternative, HBV-unrelated viruses can act as helper viruses for HDV. In vitro, envelope GPs from several virus genera, including vesiculovirus, flavivirus and hepacivirus, can package HDV RNPs, allowing efficient egress of HDV particles in the extracellular milieu of co-infected cells and subsequent entry into cells expressing the relevant receptors. Furthermore, HCV can propagate HDV infection in the liver of co-infected humanized mice for several months. Further work is necessary to evaluate whether HDV is currently transmitted by HBV-unrelated viruses in humans.

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Section: Discussionmentioning

confidence: 99%

Enveloped viruses distinct from HBV induce dissemination of hepatitis D virus in vivo

et al. 2019

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“…HDV infection causes the most severe form of viral hepatitis; patients with HDV present with high levels of ALT, aspartate aminotransferase (AST) and gamma-glutamyltransferase, and low prothrombin levels, all of which are indicative of liver damage. 12,27,28 The mechanisms involved in the pathogenesis of the disease remain unresolved. 2,28 HDV, similar to HBV and HCV, is a non-cytopathic virus and the viruses share pathogenic similarities, characterized by chronic inflammation, hepatocyte injury and progressive fibrosis.…”

Section: Discussionmentioning

confidence: 99%

“…12,27,28 The mechanisms involved in the pathogenesis of the disease remain unresolved. 2,28 HDV, similar to HBV and HCV, is a non-cytopathic virus and the viruses share pathogenic similarities, characterized by chronic inflammation, hepatocyte injury and progressive fibrosis. 8,9 For this reason, it has been assumed that the liver damage observed in HDV-infected patients, as it has been described for HBV and HCV, is also caused by components (cells, cytokines) of the host immune system.…”

Section: Discussionmentioning

confidence: 99%

TNF-alpha inhibition ameliorates HDV-induced liver damage in a mouse model of acute severe infection

et al. 2020

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Background & Aims: HDV infection induces the most severe form of human viral hepatitis. However, the specific reasons for the severity of the disease remain unknown. Recently, we developed an HDV replication mouse model in which, for the first time, liver damage was detected. Methods: HDV and HBV replication-competent genomes and HDV antigens were delivered to mouse hepatocytes using adeno-associated vectors (AAVs). Aminotransferase elevation, liver histopathology, and hepatocyte death were evaluated and the immune infiltrate was characterized. Liver transcriptomic analysis was performed. Mice deficient for different cellular and molecular components of the immune system, as well as depletion and inhibition studies, were employed to elucidate the causes of HDV-mediated liver damage. Results: AAV-mediated HBV/HDV coinfection caused hepatocyte necrosis and apoptosis. Activated T lymphocytes, natural killer cells, and proinflammatory macrophages accounted for the majority of the inflammatory infiltrate. However, depletion studies and the use of different knockout mice indicated that neither T cells, natural killer cells nor macrophages were necessary for HDV-induced liver damage. Transcriptomic analysis revealed a strong activation of type I and II interferon (IFN) and tumor necrosis factor (TNF)-a pathways in HBV/HDV-coinfected mice. While the absence of IFN signaling had no effect, the use of a TNF-a antagonist resulted in a significant reduction of HDV-associated liver injury. Furthermore, hepatic expression of HDAg resulted in the induction of severe liver damage, which was T cell-and TNF-a-independent. Conclusions: Both host (TNF-a) and viral (HDV antigens) factors play a relevant role in HDV-induced liver damage. Importantly, pharmacological inhibition of TNF-a may offer an attractive strategy to aid control of HDV-induced acute liver damage.

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“…In an early study of 75 patients with chronic hepatitis (HBsAg carriers with intrahepatic delta antigen) at enrolment, 39% developed cirrhosis or liver failure after a follow up (FU) of up to 6 years [ 26 ]. The same cohort was later followed for an average of 12 years [ 40 ], and the proportion of cirrhosis increased with the duration of follow-up, i.e., 23%, 41%, and 77% in the first, second, and third decade of disease, respectively. The progression to cirrhosis after an average 20-year follow-up was somehow less (42%) in another more recent, retrospective, large series from Italy [ 39 ].…”

Section: The Three Moirai Of Hdv Infection and Their Clinical Outcome: From Hdv-hbv Co- Or Super-infection To Hdv Mono-infectionmentioning

confidence: 99%

HDV Pathogenesis: Unravelling Ariadne’s Thread

Tseligka

Clément

Negro

2021

Viruses

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Hepatitis Delta virus (HDV) lies in between satellite viruses and viroids, as its unique molecular characteristics and life cycle cannot categorize it according to the standard taxonomy norms for viruses. Being a satellite virus of hepatitis B virus (HBV), HDV requires HBV envelope glycoproteins for its infection cycle and its transmission. HDV pathogenesis varies and depends on the mode of HDV and HBV infection; a simultaneous HDV and HBV infection will lead to an acute hepatitis that will resolve spontaneously in the majority of patients, whereas an HDV super-infection of a chronic HBV carrier will mainly result in the establishment of a chronic HDV infection that may progress towards cirrhosis, liver decompensation, and hepatocellular carcinoma (HCC). With this review, we aim to unravel Ariadne’s thread into the labyrinth of acute and chronic HDV infection pathogenesis and will provide insights into the complexity of this exciting topic by detailing the different players and mechanisms that shape the clinical outcome.

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Chronic HDV (hepatitis delta virus) hepatitis

Cited by 61 publications

References 17 publications

Enveloped viruses distinct from HBV induce dissemination of hepatitis D virus in vivo

Enveloped viruses distinct from HBV induce dissemination of hepatitis D virus in vivo

TNF-alpha inhibition ameliorates HDV-induced liver damage in a mouse model of acute severe infection

HDV Pathogenesis: Unravelling Ariadne’s Thread

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