Chronic hepatitis D (CHD) is the most severe form of chronic viral hepatitis but its role in the development of hepatocellular carcinoma (HCC) remains debated. We conducted a systematic review and ...meta-analysis of epidemiological studies to examine whether CHD is associated with an increased risk of HCC.
We searched PubMed, Embase and Web of Science, as well as study references and conference proceedings. We considered cohort and case-control studies allowing the calculation of effect estimates for the association between CHD (exposure) and HCC (outcome) in comparison to chronic hepatitis B. Data extraction and quality evaluation (using the Newcastle-Ottawa scale) were performed independently by 2 authors. Data were pooled using random-effects models.
Ninety-three studies (68 case-control studies including 22,862 patients and 25 cohort studies including 75,427 patients) were included. Twelve studies accounted for confounders, in either study design or analysis (10 of which were cohorts), and 11 cohorts were prospective. The overall analysis showed a significantly increased risk of HCC in patients with CHD, despite substantial study heterogeneity (pooled odds ratio 1.28; 95% CI 1.05–1.57; I2 = 67.0%). The association was particularly strong in the absence of heterogeneity for prospective cohort studies (pooled odds ratio 2.77; 95% CI 1.79–4.28; I2 = 0%), and studies with HIV-infected patients (pooled odds ratio 7.13; 95% CI 2.83–17.92; I2 = 0%).
We found a significantly higher risk of HCC in patients with CHD. Although further studies are needed to definitively exclude a potential bias due to antiviral treatments, our findings highlight the rationale for improved screening of hepatitis D virus infection in patients with chronic hepatitis B, and the urgent need for novel and effective antiviral therapies.
Hepatitis D virus (HDV) is a defective pathogen requiring hepatitis B virus (HBV) to complete its life cycle. Chronic hepatitis D is the most severe form of chronic viral hepatitis, increasing the risk of cirrhosis, liver decompensation and death compared to HBV monoinfection. However, the association between HDV infection and increased risk of hepatocellular carcinoma is debated. We conducted a systematic review and found that patients with HDV infection had a significantly higher risk of developing hepatocellular carcinoma than those with HBV monoinfection.
Display omitted
•HDV infection is associated with an increased risk of HCC in HBV-infected patients.•The association is stronger in high quality and/or prospective cohort studies.•The association between HDV and HCC is stronger in the setting of HIV coinfection.
Over the last century, the number of epidemics caused by RNA viruses has increased and the current SARS-CoV-2 pandemic has taught us about the compelling need for ready-to-use broad-spectrum ...antivirals. In this scenario, natural products stand out as a major historical source of drugs. We analyzed the antiviral effect of 4 stilbene dimers 1 (trans-δ-viniferin); 2 (11’,13’-di-O-methyl-trans-δ-viniferin), 3 (11,13-di-O-methyl-trans-δ-viniferin); and 4 (11,13,11’,13’-tetra-O-methyl-trans-δ-viniferin) obtained from plant substrates using chemoenzymatic synthesis against a panel of enveloped viruses. We report that compounds 2 and 3 display a broad-spectrum antiviral activity, being able to effectively inhibit several strains of Influenza Viruses (IV), SARS-CoV-2 Delta and, to some extent, Herpes Simplex Virus 2 (HSV-2). Interestingly, the mechanism of action differs for each virus. We observed both a direct virucidal and a cell-mediated effect against IV, with a high barrier to antiviral resistance; a restricted cell-mediated mechanism of action against SARS-CoV-2 Delta and a direct virustatic activity against HSV-2. Of note, while the effect was lost against IV in tissue culture models of human airway epithelia, the antiviral activity was confirmed in this relevant model for SARS-CoV-2 Delta. Our results suggest that stilbene dimer derivatives are good candidate models for the treatment of enveloped virus infections.
Display omitted
•Fungal enzymatic secretome was used to generate antimicrobial stilbene dimers.•The antimicrobial action relies on their ability to disrupt plasma membranes.•Broad spectrum activity VS Influenza Virus, Sars-CoV-2 and Herpes Simplex Virus 2.•Low toxicity and high genetic barrier to antiviral resistance.
At the end of the xixth century, the French were faced with the cultural heritage of Laos, which they had just colonised. The concept of cultural heritage, which began in the West, was brought into ...the country by agents who applied the same western regulations used in France. In Vientiane, the old capital, which had not recovered from the 1828 sacking by the Siamese, most pagodas were still in ruins. The French and the Lao, that is lao language speakers, contributed to their conservation, using different methods. The French carried out studies of the most important temples in Vientiane, in an effort to eventually restore them, since they were seen as ”historical monuments”. Despite colonisation, the French maintained a good relationship with the Lao by using peaceful methods to conserve their culture. For the Lao, the important thing was to make such places of buddhist cult come to life again, so the restoration of many ruined pagodas was undertaken by monks and villagers of neighbouring quarters. Moreover, temples played an important role in structuring the town, shaping its quarters and giving identity to their communities.
Display omitted
•Hepatitis D virus is a defective virus, dependent on hepatitis B virus for its assembly.•Hepatitis D virus infection affects 62–72 million people worldwide.•Chronic hepatitis D is ...the most severe chronic viral hepatitis.•Current interferon-based antiviral treatments have dismal efficiency and are poorly tolerated.•Host-targeting molecules inhibiting the viral life cycle are currently in clinical development.
Hepatitis delta virus (HDV) is a defective virus that requires the hepatitis B virus (HBV) to complete its life cycle in human hepatocytes. HDV virions contain an envelope incorporating HBV surface antigen protein and a ribonucleoprotein containing the viral circular single-stranded RNA genome associated with both forms of hepatitis delta antigen, the only viral encoded protein. Replication is mediated by the host cell DNA-dependent RNA polymerases. HDV infects up to72 million people worldwide and is associated with an increased risk of severe and rapidly progressive liver disease. Pegylated interferon-alpha is still the only available treatment for chronic hepatitis D, with poor tolerance and dismal success rate. Although the development of antivirals inhibiting the viral replication is challenging, as HDV does not possess its own polymerase, several antiviral molecules targeting other steps of the viral life cycle are currently under clinical development: Myrcludex B, which blocks HDV entry into hepatocytes, lonafarnib, a prenylation inhibitor that prevents virion assembly, and finally REP 2139, which is thought to inhibit HBsAg release from hepatocytes and interact with hepatitis delta antigen. This review updates the epidemiology, virology and management of HDV infection.
Using newly generated monoclonal antibodies, we have compared the distribution of β- and γ-cytoplasmic actin in fibroblastic and epithelial cells, in which they play crucial roles during various key ...cellular processes. Whereas β-actin is preferentially localized in stress fibers, circular bundles and at cell-cell contacts, suggesting a role in cell attachment and contraction, γ-actin displays a more versatile organization, according to cell activities. In moving cells, γ-actin is mainly organized as a meshwork in cortical and lamellipodial structures, suggesting a role in cell motility; in stationary cells, γ-actin is also recruited into stress fibers. β-actin-depleted cells become highly spread, display broad protrusions and reduce their stress-fiber content; by contrast, γ-actin-depleted cells acquire a contractile phenotype with thick actin bundles and shrinked lamellar and lamellipodial structures. Moreover, β- and γ-actin depleted fibroblasts exhibit distinct changes in motility compared with their controls, suggesting a specific role for each isoform in cell locomotion. Our results reveal new aspects of β- and γ-actin organization that support their functional diversity.
Lorsqu’en 2001, l’Institut national de recherche d’archéologie préventive (Inrap) a été créé, c’est une petite révolution qui s’est opérée dans le monde de l’archéologie en général. À partir de ce ...moment, l’État français a reconnu l’utilité publique de la sauvegarde du patrimoine menacé par les aménagements du territoire, et rendu obligatoires les diagnostics et les fouilles qui peuvent en découler. La mission de l’Inrap, outre le fait de procéder à des fouilles avant la destruction du sous-s...
IntroductionAcquired brain injury (ABI) in paediatrics refers to children born with a neurological deficit, which will lead to a chronic neurological disorder. As advances in medical paediatric ...health progress, we are seeing these ABI youth transitioning into adult healthcare services while also going through different life events. Despite the growing number of young adult patients, access to transition programmes to facilitate the transition process is still limited and evidence on the effectiveness of these programmes is inconclusive. The purpose of this paper is to provide the protocol for an upcoming systematic literature review on this important issue.Methods and analysisThe start of this systematic literature review is planned for 1 October 2019 and will end on 31 December 2021. According to the PICO framework developed, the Population and the Problem of interest (P) will include children, adolescents and young adults (0–18 years) diagnosed with ABI. The selected articles will have to involve an Intervention (I) relating to the healthcare of this population or life transitions from paediatric to adult-oriented care. Studies will be included if a Comparator (C) intervention was used. The expected Outcomes (O) will have to report quantitative or qualitative health-related outcomes post-transition. This comprehensive search of peer-reviewed literature will include articles published between 2010 and 2020. The databases to be searched include Medline, All EBM Reviews, Embase, PsycINFO and CINAHL. The selected articles will be appraised using the Mixed Methods Appraisal Tool. A synthesis of the findings will be drafted to identify the effectiveness of available transition programmes as well as predictors, factors and determinants involved in the transition process.Ethics and disseminationThis project is not associated with direct individuals. The dissemination plan includes strategies such as using this systematic literature review to develop a research project on transition that will be published.
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.
PDF
