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Journal of Hepatology Aug 2023Hepatitis D virus (HDV) is a defective virus that requires the hepatitis B virus to complete its life cycle and cause liver damage in humans. HDV is responsible for rare...
Hepatitis D virus (HDV) is a defective virus that requires the hepatitis B virus to complete its life cycle and cause liver damage in humans. HDV is responsible for rare acute and chronic liver diseases and is considered the most aggressive hepatitis virus. Acute infection can cause acute liver failure, while persistent infection typically causes a severe form of chronic hepatitis which is associated with rapid and frequent progression to cirrhosis and its end-stage complications, hepatic decompensation and hepatocellular carcinoma. Major diagnostic and therapeutic innovations prompted the EASL Governing Board to commission specific Clinical Practice Guidelines on the identification, virologic and clinical characterisation, prognostic assessment, and appropriate clinical and therapeutic management of HDV-infected individuals.
Topics: Humans; Hepatitis Delta Virus; Hepatitis D; Carcinoma, Hepatocellular; Liver Neoplasms; Hepatitis B virus
PubMed: 37364791
DOI: 10.1016/j.jhep.2023.05.001 -
The New England Journal of Medicine Jul 2023
Review
Topics: Humans; Hepatitis Delta Virus; Hepatitis D; Hepatitis B Surface Antigens; Hepatitis B virus
PubMed: 37407002
DOI: 10.1056/NEJMra2212151 -
Digestive Diseases and Sciences Aug 2023Hepatitis D virus (HDV) depends on hepatitis B virus (HBV) to enter and exit hepatocytes and to replicate. Despite this dependency, HDV can cause severe liver disease.... (Review)
Review
Hepatitis D virus (HDV) depends on hepatitis B virus (HBV) to enter and exit hepatocytes and to replicate. Despite this dependency, HDV can cause severe liver disease. HDV accelerates liver fibrosis, increases the risk of hepatocellular carcinoma, and hastens hepatic decompensation compared to chronic HBV monoinfection. The Chronic Liver Disease Foundation (CLDF) formed an expert panel to publish updated guidelines on the testing, diagnosis, and management of hepatitis delta virus. The panel group performed network data review on the transmission, epidemiology, natural history, and disease sequelae of acute and chronic HDV infection. Based on current available evidence, we provide recommendations for screening, testing, diagnosis, and treatment of hepatitis D infection and review upcoming novel agents that may expand treatment options. The CLDF recommends universal HDV screening for all patients who are Hepatitis B surface antigen-positive. Initial screening should be with an assay to detect antibodies generated against HDV (anti-HDV). Patients who are positive for anti-HDV IgG antibodies should then undergo quantitative HDV RNA testing. We also provide an algorithm that describes CLDF recommendations on the screening, diagnosis, testing, and initial management of Hepatitis D infection.
Topics: Coinfection; Humans; Hepatitis Delta Virus; Hepatitis D; Superinfection; Hepatitis B virus
PubMed: 37338616
DOI: 10.1007/s10620-023-07960-y -
Viruses Jun 2021Hepatitis delta virus (HDV) is a defective human virus that lacks the ability to produce its own envelope proteins and is thus dependent on the presence of a helper... (Review)
Review
Hepatitis delta virus (HDV) is a defective human virus that lacks the ability to produce its own envelope proteins and is thus dependent on the presence of a helper virus, which provides its surface proteins to produce infectious particles. Hepatitis B virus (HBV) was so far thought to be the only helper virus described to be associated with HDV. However, recent studies showed that divergent HDV-like viruses could be detected in fishes, birds, amphibians, and invertebrates, without evidence of any HBV-like agent supporting infection. Another recent study demonstrated that HDV can be transmitted and propagated in experimental infections ex vivo and in vivo by different enveloped viruses unrelated to HBV, including hepatitis C virus (HCV) and flaviviruses such as Dengue and West Nile virus. All this new evidence, in addition to the identification of novel virus species within a large range of hosts in absence of HBV, suggests that deltaviruses may take advantage of a large spectrum of helper viruses and raises questions about HDV origins and evolution.
Topics: Animals; Evolution, Molecular; Genome, Viral; Helper Viruses; Hepatitis D; Hepatitis Delta Virus; Host Specificity; Humans; Phylogeny; Viral Proteins; Virus Replication
PubMed: 34201626
DOI: 10.3390/v13071207 -
Nature Feb 2019A stable latent reservoir for HIV-1 in resting CD4 T cells is the principal barrier to a cure. Curative strategies that target the reservoir are being tested and require...
A stable latent reservoir for HIV-1 in resting CD4 T cells is the principal barrier to a cure. Curative strategies that target the reservoir are being tested and require accurate, scalable reservoir assays. The reservoir was defined with quantitative viral outgrowth assays for cells that release infectious virus after one round of T cell activation. However, these quantitative outgrowth assays and newer assays for cells that produce viral RNA after activation may underestimate the reservoir size because one round of activation does not induce all proviruses. Many studies rely on simple assays based on polymerase chain reaction to detect proviral DNA regardless of transcriptional status, but the clinical relevance of these assays is unclear, as the vast majority of proviruses are defective. Here we describe a more accurate method of measuring the HIV-1 reservoir that separately quantifies intact and defective proviruses. We show that the dynamics of cells that carry intact and defective proviruses are different in vitro and in vivo. These findings have implications for targeting the intact proviruses that are a barrier to curing HIV infection.
Topics: CD4-Positive T-Lymphocytes; Carrier State; Cell Line; DNA, Viral; Defective Viruses; HIV Infections; HIV-1; Humans; Lymphocyte Activation; Polymerase Chain Reaction; Proviruses; Virus Latency
PubMed: 30700913
DOI: 10.1038/s41586-019-0898-8 -
Seminars in Liver Disease Feb 2018New therapeutic strategies to treat chronic hepatitis D are directed to deprive the hepatitis D virus (HDV) of functions necessary to complete its life cycle that are... (Review)
Review
New therapeutic strategies to treat chronic hepatitis D are directed to deprive the hepatitis D virus (HDV) of functions necessary to complete its life cycle that are provided by the hepatitis B virus (HBV) and by the host. Current options are (1) the block by the synthetic peptide Myrcludex B of HBV surface antigen (HBsAg) entry into cells through the inhibition of the sodium taurocholate cotransporting receptor; (2) the inhibition with lonafarnib of the farnesylation of the large HD antigen, required for virion assembly; (3) the presumed reduction by the nucleic acid polymer REP 2139 of the release of the HBsAg and subviral HBV particles necessary for HD virion morphogenesis. Lonafarnib and Myrcludex in monotherapy reduced serum HDV-RNA but did not reduce the HBsAg and HD viremia rebounded after therapy; they may provide additional efficacy to pegylated interferon alpha (Peg IFN-α) therapy. Treatment with REP-2139 in combination with Peg IFN-α induced a sustained clearance both of the HDV-RNA and HBsAg in 5 of 12 patients, providing the best interim results so far obtained in the therapy of chronic hepatitis D.
Topics: Animals; Antiviral Agents; DNA, Viral; Drug Resistance, Viral; Hepatitis D, Chronic; Hepatitis Delta Virus; Humans; Molecular Targeted Therapy; Sustained Virologic Response; Treatment Outcome; Viral Load
PubMed: 29471567
DOI: 10.1055/s-0037-1621711 -
Viruses Feb 2022Virus-like particles resemble infectious virus particles in size, shape, and molecular composition; however, they fail to productively infect host cells. Historically,... (Review)
Review
Virus-like particles resemble infectious virus particles in size, shape, and molecular composition; however, they fail to productively infect host cells. Historically, the presence of virus-like particles has been inferred from total particle counts by microscopy, and infectious particle counts or plaque-forming-units (PFUs) by plaque assay; the resulting ratio of particles-to-PFUs is often greater than one, easily 10 or 100, indicating that most particles are non-infectious. Despite their inability to hijack cells for their reproduction, virus-like particles and the defective genomes they carry can exhibit a broad range of behaviors: interference with normal virus growth during co-infections, cell killing, and activation or inhibition of innate immune signaling. In addition, some virus-like particles become productive as their multiplicities of infection increase, a sign of cooperation between particles. Here, we review established and emerging methods to count virus-like particles and characterize their biological functions. We take a critical look at evidence for defective interfering virus genomes in natural and clinical isolates, and we review their potential as antiviral therapeutics. In short, we highlight an urgent need to better understand how virus-like genomes and particles interact with intact functional viruses during co-infection of their hosts, and their impacts on the transmission, severity, and persistence of virus-associated diseases.
Topics: Animals; Colony-Forming Units Assay; Defective Viruses; Genome, Viral; Humans; Microscopy, Electron, Transmission; Viral Plaque Assay; Virion; Virus Diseases; Virus Replication
PubMed: 35215979
DOI: 10.3390/v14020383 -
Liver International : Official Journal... May 2024
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Hepatitis Delta Virus; Virus Diseases
PubMed: 38634678
DOI: 10.1111/liv.15882 -
Viruses Jun 2020Hepatitis delta virus (HDV) and hepatitis B virus (HBV) are blood-borne viruses that infect human hepatocytes and cause significant liver disease. Infections with HBV... (Review)
Review
Hepatitis delta virus (HDV) and hepatitis B virus (HBV) are blood-borne viruses that infect human hepatocytes and cause significant liver disease. Infections with HBV are more damaging when there is a coinfection with HDV. The genomes and modes of replication of these two viruses are fundamentally different, except for the fact that, in nature, HDV replication is dependent upon the envelope proteins of HBV to achieve assembly and release of infectious virus particles, ones that use the same host cell receptor. This review focuses on what has been found of the various ways, natural and experimental, by which HDV particles can be assembled and released. This knowledge has implications for the prevention and treatment of HDV infections, and maybe for an understanding of the origin of HDV.
Topics: Animals; Hepatitis D; Hepatitis Delta Virus; Humans; Virus Replication
PubMed: 32560053
DOI: 10.3390/v12060648 -
Viruses May 2021Hepatitis D virus (HDV) is a small, defective RNA virus that depends on hepatitis B virus (HBV) for virion assembly and transmission. It replicates within the nucleus of... (Review)
Review
Hepatitis D virus (HDV) is a small, defective RNA virus that depends on hepatitis B virus (HBV) for virion assembly and transmission. It replicates within the nucleus of hepatocytes and interacts with several cellular proteins. Chronic hepatitis D is a severe and progressive disease, leading to cirrhosis in up to 80% of cases. A high proportion of patients die of liver decompensation or hepatocellular carcinoma (HCC), but the lack of large prospective studies has made it difficult to precisely define the rate of these long-term complications. In particular, the question of whether HDV is an oncogenic virus has been a matter of debate. Studies conducted over the past decade provided evidence that HDV is associated with a significantly higher risk of developing HCC compared to HBV monoinfection. However, the mechanisms whereby HDV promotes liver cancer remain elusive. Recent data have demonstrated that the molecular profile of HCC-HDV is unique and distinct from that of HBV-HCC, with an enrichment of upregulated genes involved in cell-cycle/DNA replication, and DNA damage and repair, which point to genome instability as an important mechanism of HDV hepatocarcinogenesis. These data suggest that HBV and HDV promote carcinogenesis by distinct molecular mechanisms despite the obligatory dependence of HDV on HBV.
Topics: Carcinogenesis; Carcinoma, Hepatocellular; Genome, Viral; Hepatitis B virus; Hepatitis D; Hepatitis D, Chronic; Hepatitis Delta Virus; Hepatocytes; Humans; Liver Cirrhosis; Liver Neoplasms; RNA, Viral; Virus Assembly
PubMed: 34064419
DOI: 10.3390/v13050830