Search Results (95)

Hepatitis B virus (HBV) infection is one of the most dangerous viral diseases, with innate immunity representing the first line of defense against the virus. In this branch of the immune system, neutrophils are considered key cellular mediators. To better understand the implication of neutrophils in the distinct stages of the disease, HBV-infected patients were enrolled in this study and categorized into three groups: patients with acute infection, chronic infection under treatment, and at early cirrhotic stage. To elucidate the role of inflammatory mediators and cellular mechanisms of neutrophilic origin in the course of the infection, both ex vivo and in vitro studies were performed. Increased levels of C-C motif chemokine ligand 2 (CCL2), interleukin (IL)-18, IL-33, and citrullinated histone H3 (CitH3)—an accurate marker of neutrophil extracellular traps (NETs)—were detected in the circulation of patients with acute infection or early cirrhosis. In parallel, sera from the aforementioned patient groups induced the formation of IL-1b-bearing NETs in neutrophils from healthy individuals. These inflammatory NETs affected primary fibroblasts towards acquiring a pro-fibrotic phenotype. These results suggest that NETs could be regarded as mediators in hepatitis B manifestations, while their therapeutic targeting could enhance the management of early-stage cirrhotic patients. Full article

Italy was one of the first countries to implement a hepatitis B (HBV) immunization strategy in 1991; since its introduction, the epidemiology of this disease has significantly changed. The aim of this retrospective study was to assess the seroprevalence of three HBV markers (anti-HBs, anti-HBc, and HBsAg) and describe the acquired immunity in a representative sample of the adult general population in the province of Florence (Italy) between April 2018 and December 2019. We conducted an enzyme-linked immunosorbent assay on 430 serum samples collected from the adult general population to quantify anti-HBs titers and assess the presence of anti-HBc and HBsAg. For the interpretation of hepatitis B serologic results, we referred to the US CDC guidelines. We conducted two multivariate logistic regression analyses (applied to the entire enrolled population and to the unvaccinated) to assess predictors of immunity against HBV using sex, age, and nationality as predictors. The overall anti-HBs prevalence was 30%, with a significant decreasing trend in seropositivity with increasing age. The overall anti-HBc prevalence was 11.6%, with seropositivity increasing with age. Only one subject tested positive for HBsAg (0.2%). Approximately 67.4% (290/430) of the study population was susceptible, 20.9% (90/430) was vaccinated, 9.1% (39/430) had naturally acquired immunity, and 0.2% (1/430) had an acute infection. Older age and foreign nationality were identified as risk factors in both multivariate logistic regression models. The comparison highlights a reduction in the circulation of HBV infection markers (anti-HBc and HBsAg) over 30 years in Tuscany, particularly in younger age groups. Our seroprevalence study demonstrated a good level of protection against hepatitis B, primarily among individuals under 40 years old, the target group of the vaccination strategy. Full article

Background: The MeMed BV^® BV score is a novel, promising host-protein score, differentiating bacterial from viral infections, that combines the expression levels of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), interferon gamma-induced protein-10 (IP-10), and C-reactive protein (CRP). The aim of our study was to determine its diagnostic accuracy in hospitalized febrile children. Methods: A prospective study was performed from December 2023 to April 2024 in two pediatric clinics at “Aghia Sophia” Children’s Hospital, Athens, Greece. Patients > 3 months old, presenting with fever, clinical suspicion of acute infection, and symptoms onset up to 7 days prior were considered eligible. Patients with cancer, Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), Tuberculosis (TB), and immunodeficiency were excluded. Two pediatricians reviewed the clinical, laboratory, microbiological, and radiological data and assigned the final diagnosis. The experts were blinded to the BV scores. Results: One hundred and thirty-five patients were enrolled. The predominant medical condition was respiratory tract infection (59.3% lower, 26.7% upper). Twenty-nine (21.5%) patients were diagnosed with bacterial infections. The BV score demonstrated a sensitivity of 96.2%, specificity of 88.7%, and negative predictive value (NPV) of 98.9% for bacterial infections. Equivocal BV scores were reported in 8.9% of cases and were excluded from calculations. The area under the curve was 0.96 (95% CI: 0.93–0.99). A ROC curve analysis was performed, and the optimal cut-off score was estimated at 60, providing a sensitivity of 93.1%, specificity of 88.7%, and NPV of 97.9%. Conclusions: In our study population, the BV score showed high sensitivity and NPV in bacterial infection diagnosis. Further studies are needed to assess the possibility of replacing the “equivocal” range with a narrower one or a specific cut-off value. Full article

Background/Objectives: Immunization with the hepatitis B vaccine is the most effective means of preventing acute HBV infection. However, whether the primary vaccination of infants confers lifelong immunity remains controversial. Therefore, the ongoing surveillance of vaccine recipients is required. Methods: A longitudinal study was carried out based on LongAn county, one of the five clinical trial centers for hepatitis B immunization in China in the 1980s. Serum samples were collected and tested for HBV serological markers and DNA. Results: A total of 637 subjects born in 1987–1993 were recruited, including 503 males and 134 females. The total prevalence of HBsAg was 3.9%. The prevalence in females (8.2%) was significantly higher than that in males (2.8%) (p = 0.004). The prevalence of anti-HBc in females (52.2%) was also significantly higher than that in males (41.2%) (p = 0.021). The prevalence of anti-HBs was 42.7% and did not differ significantly between males (41.7%) and females (46.3%) (p = 0.347). Compared to data from surveillance over the last ten years, the positivity rate of HBsAg did not increase. The positivity rate of anti-HBs decreased significantly (p = 0.049) while that of anti-HBc increased significantly (p = 0.001). The prevalence of occult HBV infection (OBI) in 2024 (6.0%) was significantly higher than that in 2017 (1.6%) (p = 0.045). Subjects diagnosed with OBI in 2017 maintained occult infection in 2024. Conclusions: Neonatal HBV vaccination maintained effective protection for at least 37 years. However, the prevalence of OBI increases with age in those vaccinated at birth, raising a new issue of how to prevent and control OBI in the post-universal infant vaccination era. Full article

Background/Objectives: In chronic hepatitis B infection (CHB), the hepatitis B surface antigen (HBsAg) continuously exhausts the hepatitis B surface antibody (HBsAb), which leads to the formation of immune tolerance. Accordingly, the hepatitis B virus (HBV) infection can be blocked by inhibiting the binding of the hepatitis B surface pre-S1/pre-S2 antigen to the hepatocyte receptor NTCP, but the clinical cure rate of pre-S-based vaccines for CHB is limited. Methods: In this study, we designed and prepared multivalent hepatitis B therapeutic mRNA vaccines encoding three hepatitis B surface antigen proteins (L, M, and S) at the cell membrane, verified via in vitro transfection and expression experiments. An in vivo immunization experiment in HBV transgenic (Tg) mice was first completed. Subsequently, an adeno-associated virus plasmid vector carrying the HBV1.2-fold genome (pAAV HBV1.2) model and the adeno-associated virus vector carrying HBV1.3-fold genome (rAAV HBV1.3) model were constructed and immunized with mRNA vaccines. The HBV antigen, antibodies, and HBV DNA in serum were detected. Indirect (enzyme-linked immunosorbent assay) ELISA were made to analyze the activated antigen-specific IgG in HBV Tg mice. Antigen-dependent T-cell activation experiments were carried out, as well as the acute toxicity tests in mice. Results: The L protein/pre-S antigens could be stably presented at the cell membrane with the support of the S protein (and M protein). After vaccinations, the vaccines effectively reactivated the production of high levels of HBsAb, disrupted immune tolerance, and activated the production of high-affinity antibodies against structural pre-S antigen in HBV Tg mice. The HBsAg seroconversion and serum HBV DNA clearance were achieved in two HBV mice models. Furthermore, pre-S antigen-dependent T-cell response against HBV infection was confirmed. The therapeutic vaccine also showed safety in mice. Conclusions: A novel therapeutic mRNA vaccine was developed to break through HBsAg-mediated immune tolerance and treat CHB by stably presenting the pre-S antigen at the membrane, and the vaccine has great potential for the functional cure of CHB. Full article

Hepatitis B virus (HBV) is a major global health concern, affecting millions of people worldwide. HBV is part of the hepadnaviridae family and one of the primary causes of acute and chronic liver infections, leading to conditions such as cirrhosis and hepatocellular carcinoma (HCC). Understanding the intracellular transport and genome repair mechanisms of HBV is crucial for developing new drugs, which—in combination with immune modulators—may contribute to potential cures. This review will explore the current knowledge of HBV intracytoplasmic and nuclear transport, as well as genome repair processes, while drawing comparisons to other viruses with nuclear replication. Full article

The effects of a concomitant infection of hepatitis B virus (HBV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are still debated, with a recognized major risk of HBV reactivation during immune-suppressive treatments. The aim of this study was to determine the prevalence and predictive factors of HBV reactivation in a cohort of hospitalized patients with coronavirus disease 2019 (COVID-19) and a current or past hepatitis B infection. In a monocentric retrospective observational study, we enrolled all consecutive hospital admitted patients with COVID-19 pneumonia and a positive HBV serology (N = 84) in our Infectious Diseases Unit from April 2021 to December 2023. We identified 18 (21%) HBsAg-positive/anti-HBc-positive, 41 (49%) HBsAg-negative/anti-HBc-positive/anti-HBs-positive, and 25 (30%) HBsAg-negative/anti-HBc-positive/anti-HBs-negative subjects. The overall rate of hepatitis flare was 10.7%, without any HBsAg seroreversion, severe HBV reactivation, and/or need for new HBV antiviral therapy introduction. Systemic corticosteroid treatment for COVID-19 and baseline anti-HBsAg status were associated with this risk of HBV reactivation. In conclusion, the overall risk of hepatitis flares in hospitalized COVID-19 was reasonably low, with higher doses of corticosteroids treatment being the major risk factor for HBV reactivation, and anti-HBs-positive serological status as a protective element. Full article

Background. Causing approximately 8 million deaths each year, tobacco smoking represents a significant public health concern. Evidence shows that smoking significantly impairs antibody production and immune cell activity following vaccination. Objectives. This review aims to provide a comprehensive overview of the literature regarding how smoking reduces the effectiveness of active immunization by affecting vaccine-induced immune response. Methods. This study was performed according to the PRISMA guidelines, and the protocol was registered on the PROSPERO platform (ID: CRD42024582638). PubMed, Scopus and Web of Science were consulted as bibliographic and citation databases. Studies published in Italian and English and that aimed to investigate the effects of exposure to active and passive tobacco smoking on vaccine-induced immune response were included. Results. Thirty-four studies were selected. Overall, a decrease in antibody levels and avidity and in immune cell production were observed in individuals exposed to smoke. The meta-analysis showed a weighted mean difference between smokers and non-smokers equal to 0.65 (95% CI: 0.10–1.19, p = 0.02) for vaccinations against COVID-19, influenza, pneumococcus, HBV, HPV, tetanus, pertussis, polio, haemophilus influenzae type b, measles–mumps–rubella, and recurrent urinary tract infections. Conclusions. Smoking cessation campaigns should be considered in order to increase the effectiveness of vaccination programs. Furthermore, the opportunity to adopt different vaccine dosing schemes for smokers and non-smokers, especially in acute epidemics, should be considered. Full article

Cells have developed various mechanisms to counteract viral infections. In an evolutionary arms race, cells mobilize cellular restriction factors to fight off viruses, targeted by viral factors to facilitate their own replication. The hepatitis B virus (HBV) is a small dsDNA virus that causes acute and chronic infections of the liver. Its genome persists in the nuclei of infected hepatocytes as a covalently closed circular DNA (cccDNA) minichromosome, thus building up an episomal persistence reservoir. The chromosomal maintenance complex SMC5/6 acts as a restriction factor hindering cccDNA transcription, whereas the viral regulatory protein HBx targets SMC5/6 for proteasomal degradation, thus relieving transcriptional suppression of the HBV minichromosome. To date, no curative therapies are available for chronic HBV carriers. Knowledge of the factors regulating the cccDNA and the development of therapies involving silencing the minichromosome or specifically interfering with the HBx-SMC5/6 axis holds promise in achieving sustained viral control. Here, we summarize the current knowledge of the mechanism of SMC5/6-mediated HBV restriction. We also give an overview of SMC5/6 cellular functions and how this compares to the restriction of other DNA viruses. We further discuss the therapeutic potential of available and investigational drugs interfering with the HBx-SMC5/6 axis. Full article

Hepatitis E virus (HEV) is a common cause of acute hepatitis, with increasing incidence in Europe, including Romania. Concurrently, Romania has a high prevalence of chronic hepatitis B (CHB). There is limited research on the clinical presentation and outcomes of HEV infection in patients with pre-existing chronic hepatitis B (CHB), especially in resource-rich settings. Most literature data come from South, East, and Southeast Asia. A review of the literature on HEV and HBV co-infection indicates a severe prognosis, particularly in patients with underlying liver disease. However, the cases in this study, which did not display cirrhosis, showed varied outcomes. The role of anti-HBV treatment in improving prognosis remains uncertain and warrants further investigation. Acute HEV infection superimposed on chronic HBV infection poses significant clinical challenges, with outcomes ranging from full recovery to fatality. Preventive measures, including sanitation and vaccination against HBV, are crucial. More studies are needed to establish effective treatment protocols for this co-infection. In this study, we will analyze the clinical setting, diagnosis, particularities, and outcomes of five such cases of dual hepatotropic viral infection recorded over a period of 6 years (2018–2023) at a large Infectious Diseases clinic in Bucharest, Romania. Full article

Background: We aim to investigate the characteristics of invasive pulmonary aspergillosis (IPA) in patients with HBV-related acute on chronic liver failure (HBV-ACLF). Methods: A total of 44 patients with probable IPA were selected as the case group, and another 88 patients without lung infections were chosen as the control group. Results: HBV-ACLF patients with probable IPA had more significant 90-day mortality (38.6% vs. 15.9%, p = 0.0022) than those without. The white blood cell (WBC) count was the independent factor attributed to the IPA development [odds ratio (OR) 1.468, p = 0.027]. Respiratory failure was associated with the mortality of HBV-ACLF patients with IPA [OR 26, p = 0.000]. Twenty-seven patients received voriconazole or voriconazole plus as an antifungal treatment. Plasma voriconazole concentration measurements were performed as therapeutic drug monitoring in 55.6% (15/27) of the patients. The drug concentrations exceeded the safe range with a reduced dosage. Conclusions: The WBC count might be used to monitor patients’ progress with HBV-ACLF and IPA. The presence of IPA increases the 90-day mortality of HBV-ACLF patients mainly due to respiratory failure. An optimal voriconazole regimen is needed for such critical patients, and voriconazole should be assessed by closely monitoring blood levels. Full article

The hepatitis delta virus (HDV) is a unique pathogen with significant global health implications, affecting individuals who are coinfected with the hepatitis B virus (HBV). HDV infection has profound clinical consequences, manifesting either as coinfection with HBV, resulting in acute hepatitis and potential liver failure, or as superinfection in chronic HBV cases, substantially increasing the risk of cirrhosis and hepatocellular carcinoma. Given the complex dynamics of HDV infection and the urgent need for advanced research tools, this article introduces vHDvDB 2.0, a comprehensive HDV full-length sequence database. This innovative platform integrates data preprocessing, secondary structure prediction, and epidemiological research tools. The primary goal of vHDvDB 2.0 is to consolidate HDV sequence data into a user-friendly repository, thereby facilitating access for researchers and enhancing the broader scientific understanding of HDV. The significance of this database lies in its potential to streamline HDV research by providing a centralized resource for analyzing viral sequences and exploring genotype-specific characteristics. It will also enable more in-depth research within the HDV sequence domains. Full article

Viral hepatitis is the main cause of infectious liver disease. During pregnancy, a risk of vertical transmission exists both during gestation and at birth. HAV, HBV, and HCV might progress similarly in pregnant and non-pregnant women. In this study, we found a prevalence of 0.22% of viral hepatitis in pregnant women, with a light preponderance of HCV over HAV and HBV. Here, it was observed that acute HAV infection is more symptomatic and has higher risks for the mother and fetus, in a similar manner to what has been reported for HEV. Histopathological alterations were observed in all except one placenta, indicating that it is an important tissue barrier. Regarding the Mexican strategies for viral hepatitis eradication, success may be related to vaccination at birth, whereas for HCV, the national program for eradication is aimed at treating the infection via direct-acting antiviral agents. The HBV strategy has positively impacted pregnant women and their children, diminishing the risk of vertical transmission. The HCV strategy is still in its early years, and it is expected to be just as successful. For acute hepatitis, HAV and HEV, programs promoting hand washing and those aimed at providing clean food and water are applicable as preventive strategies, alongside other programs such as vaccination. Full article

The aim of this study was to analyse the impact of the introduction of universal adolescent HBV vaccination on the incidence of acute hepatitis B virus (HBV) infections. Acute HBV cases reported to the Spanish National Epidemiological Surveillance Network between 2005 and 2021 were included. For regions starting adolescent vaccination in 1991–1993 and in 1994–1996, HBV incidence rates were compared by calculating the incidence rate ratio (IRR) and 95% confidence interval (CI). We also analysed the 2017 Spanish national seroprevalence survey data. The overall acute HBV incidence per 100,000 persons was 1.54 in 2005 and 0.64 in 2021 (p < 0.001). The incidence in 2014–2021 was lower for regions that started adolescent vaccination in 1991–1993 rather than in 1994–1996 (IRR 0.76; 95% CI 0.72–0.83; p < 0.001). In the 20–29 age group, incidence in regions that started adolescent vaccination in 1991–1993 was also lower (IRR 0.87; 95% CI 0.77–0.98; p = 0.02 in 2005–2013 and IRR 0.71; 95% CI 0.56–0·90; p < 0.001 in 2014–2021). Anti-HBc prevalence in the 35–39 age group was lower in the regions that started vaccination earlier, although the difference was not statistically significant (p = 0.09). Acute HBV incidence decreased more in the young adult population in regions that began adolescent vaccination earlier. Maintaining high universal vaccination coverage in the first year of life and in at-risk groups is necessary to achieve HBV elimination by 2030. Full article