Search Results (1,817)

The hepatitis B virus (HBV) is a DNA virus of major public health concern whose error-prone polymerase has driven the emergence of ten distinct genotypes and a multitude of resistance-associated mutations (RAMs). Herein, we conducted a retrospective observational study analyzing 8152 hepatitis B virus (HBV) sequences from 27 regions across the Americas, retrieved from GenBank, to construct a database and examine associations among HBV genotypes/subtypes, geographic distribution, resistance-associated mutations (RAMs), and resistance to nucleos(t)ide analogs (NAs) used in the treatment of chronic infection. Following phylogenetic analysis, mutations at clinically relevant sites in the reverse transcriptase domain were identified and classified by resistance to NAs. Genotypes A (21.1% A2 and 14.7% A1) and D predominated across the retrieved database, whereas genotypes E, G, H, and I each accounted for fewer than 3% of the sequences. Among the sequences in the database, 10.6% harbored RAMs, with genotypes G, A, and H predominating in this category. The most frequently observed RAM was L180M + M204V/I, which is associated with resistance to LMV, ETV, and TBV, whereas resistance to ADV and TDF remained rare. Genotypes G and A2 were significantly associated with a higher likelihood of harboring multiple RAMs (as evaluated by logistic regression), along with an increased risk of resistance to LMV, ETV, and TBV; the opposite was true for subtype A1. Notably, genotypes H and B5 were associated with an elevated risk of TDF resistance. A comprehensive understanding of RAMs and circulating genotypes in the Americas is essential for identifying high-risk populations and establishing geographically targeted therapeutic strategies. Full article

Introduction: Hepatitis B is the most prevalent virus that causes severe liver infection worldwide. According to the current guidelines, the HBV viral load and other factors can help in treatment decisions. Therefore, the present study explores the relationship between the HBV viral load and blood-based laboratory parameters. Methods: The HBV viral load was evaluated in blood samples from 159 HBsAg-positive patients (ICT-positive). The viral load was categorized as high (above 200,000 IU/mL), moderate (between 2000 and 200,000 IU/mL), or low (below 2000 IU/mL). The viral load was then compared with laboratory parameters. Results: A significant association was observed between the Hepatitis B viral load and the patient’s age (p < 0.01). The males showed a substantially higher viral load, with 29.2% of the male patients exhibiting elevated levels, compared to 11% of the females. A statistically significant correlation was found between the viral load and liver enzymes, specifically AST (p < 0.005) and ALT (p < 0.04), as well as calcium (p < 0.01). Notably, the elevated ALT and AST levels were more pronounced in the patients with moderate and high viral loads, suggesting a potential link to liver dysfunction. A remarkable insight uncovered in our study revolves around the notable increase in the serum calcium levels (p < 0.01). Conclusions: The AST, ALT, and serum calcium levels were the most altered parameters with high HBV viral load. Though limited reports are available on altered serum calcium levels, they could serve as potential laboratory markers for assessing disease progression in HBV infection. Moreover, focusing on potential therapies to normalize the AST, ALT, and serum calcium levels could offer promising avenues for combating HBV infection. Full article

Background/Objectives: Identifying dietary factors influencing liver cancer is crucial for developing preventive measures. While tea polyphenols have demonstrated cancer-preventive activities in animal models, the evidence in humans is not definitive. This study aims to explore the association between tea consumption and liver cancer, as well as the interaction between tea drinking and other risk factors, in China, a country with a high incidence of liver cancer and substantial tea consumption. Methods: A population-based case–control study was conducted in Jiangsu Province from 2003 to 2010. Socio-demographic data, history of tea consumption, and serum markers of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections were evaluated. Unconditional logistic regression was used to examine the associations between tea consumption and the odds of liver cancer. Potential interactions between tea consumption and other major liver cancer risk factors were assessed. Results: A total of 2011 incident liver cancer cases and 7933 controls were included in the analysis. Regular tea drinking showed an inverse association with the risk of liver cancer compared with those who never drank tea (OR: 0.79; 95% CI: 0.63–0.99). Current tea drinking showed an inverse association with liver cancer (OR: 0.51; 95% CI: 0.39–0.66), while former tea drinking showed a positive association (OR: 3.56; 95% CI: 2.42–5.23). Current tea consumption was inversely associated with liver cancer incidence among both hepatitis B surface antigen (HBsAg) positive (OR: 0.45; 95% CI: 0.28–0.73) and HBsAg negative participants (OR: 0.51, 95% CI: 0.36–0.73), among both never and ever tobacco smokers, ever alcohol drinkers (OR: 0.46; 95% CI: 0.33–0.63), and among those without family history of liver cancer. Multiplicative and additive interactions were observed between tea drinking and HBsAg, alcohol consumption, and history of raw water drinking. Conclusions: Tea consumption is inversely associated with the development of primary liver cancer, with potential interactions involving HBV infection, alcohol consumption, and raw (unsafe) water drinking. Increasing tea consumption—particularly among high-risk populations such as individuals who consume alcohol—may serve as an additional preventive measure for liver cancer. This should be considered alongside established strategies, including HBV vaccination, alcohol cessation, and avoidance of drinking raw water, to help reduce liver cancer risk. Full article

Background: The concentration of antigen-specific antibodies in serum is usually measured in international units/mL. Therefore, the actual concentration of virus-specific antibodies in sera is unknown. Objectives: The aim of the study was to determine conversion factors for concentrations of IgG against hepatitis B surface antigen (HBs), SARS-CoV-2 receptor binding domain (RBD) and nucleoprotein (NP) as well as tetanus toxin (Ttx) in serum and to compare antigen-specific IgG concentrations in serum samples. Methods: Absorption equivalence ELISAs were used to determine conversion factors for international units (IU) for anti-HBs, anti-SARS-CoV-2-RBD and NP and for anti-Ttx immunoglobulin G. The antigen-specific IgG concentrations in serum samples were then measured in units/mL and the ratio of IgG concentrations in the sera was determined using the conversion factors. Results: One IU of anti-HBs IgG corresponded to 24.4 BAU of anti-CoV-2 RBD IgG, 6.87 BAU of anti-CoV-2 NP and 14 mIU of anti-Ttx IgG. One BAU anti-SARS-CoV-2 NP-specific IgG is equivalent to 3.5 BAU SARS-CoV-2 RBD-specific IgG. Conversion of international units showed that median serum anti-Ttx-IgG concentrations were 50 times higher and anti-CoV-2-RBD-IgG concentrations were 390 times higher than median anti-HBs-IgG concentrations. In addition, after SARS-CoV-2 infection, the concentration of NP-specific IgG in serum was generally higher than that of RBD-specific IgG. Conclusions: The study provides conversion factors for serum concentrations of IgG against HBs, SARS-CoV-2 RBD and NP, as well as Ttx-IgG. This offers new insights into serum IgG concentrations and allows conclusions to be drawn about plasma cell pools. Full article

Background: Chronic hepatitis B (CHB) remains being a major public health threat, and currently existing CHB therapies have limited efficacy and side effects. We have recently developed a vaccine termed VVX001 based on a recombinant fusion protein consisting of the preS domain of the large surface protein of hepatitis B virus (HBV) fused to grass pollen allergen peptides. VVX001 has been shown to induce preS-specific antibodies in grass pollen allergic patients, and sera of immunized subjects inhibited HBV infection in vitro. Methods: In this study we investigated if immunization with VVX001 can induce preS-specific antibodies in CHB using the adeno-associated virus (AAV)-HBV murine model of CHB. Six groups of C57BL/6 female mice (n = 6) were transduced with AAV-HBV or AAV-Empty, and after six weeks, they were immunized five times with 20 µg of aluminum hydroxide-adsorbed VVX001 or preS or vehicle (Alum alone). Serum samples were taken continuously. Two weeks after the last immunization, spleen and liver mononuclear cells were collected. Serum reactivity to preS and preS-derived peptides was assessed by ELISA. B-cell responses were measured by ELISPOT assay, and intrahepatic lymphocyte (ILH) counts were determined by FACS. HBV DNA, HBsAg, HBeAg, ALT, and AST were assessed using commercial kits. Results: Our results show that VVX001 induces preS-specific IgG antibodies that cross-react with different HBV genotypes A-H and are directed against the sodium taurocholate co-transporting polypeptide (NTCP) receptor binding site of preS both in mice with and without HBV. Actively immunized AAV-HBV-treated mice had a higher number of intrahepatic lymphocytes than vehicle-vaccinated and mock-transduced animals. Conclusions: These findings encourage performing further trials to study the potential of VVX001 for therapeutic vaccination against CHB. Full article

Anthrax remains a formidable bioterrorism threat for which new, optimized and thermostable vaccines are needed. We previously demonstrated that five immunizations of rabbits with a multiple-antigenic-peptide (MAP) vaccine in either Freund’s adjuvant or human-use adjuvants can elicit antibody (Ab) against the loop-neutralizing determinant (LND), a cryptic neutralizing epitope in the 2β2-2β3 loop of protective antigen from Bacillus anthracis (B. anthracis), which mediates complete protection of rabbits from inhalation spore challenge with the B. anthracis Ames strain. To develop a more immunogenic vaccine, we molecularly constructed a virus-like particle (VLP) vaccine, comprising the Woodchuck hepatitis core antigen capsid (WHcAg) displaying 240 copies of the LND epitope on each nanoparticle. Initial studies showed that the LND-VLP was immunogenic in rabbits following two immunizations, and passive transfer of the rabbit sera into A/J mice conferred complete protection from aerosol challenge with B. anthracis. Further optimization of the vaccine revealed that the lyophilized LND-VLP vaccine was capable of eliciting highly protective levels of neutralizing antibody with two immunizations, and in some rabbits, a single immunization, using human-use adjuvants. A lyophilized LND-VLP nanoparticle vaccine may be an effective stand-alone vaccine or may complement PA-based vaccines as a future pre- or post-exposure vaccine for anthrax. Full article

Blood transfusion remains vital in healthcare but poses risks, particularly from transfusion-transmissible viral infections (TTVIs). This study aims to determine the seroprevalence of HIV, HBV, and HCV among blood donors in Borgou (Benin) in 2023. This prospective, cross-sectional study involved voluntary, non-remunerated blood donors recruited via mobile campaigns and at a fixed site from January to December 2023. Screening for HIV, HBV, and HCV was performed using fourth-generation ELISA (Biorad^®). Data analysis used SPSS with Chi-square test of independence (p < 0.05), and multiple logistic regression identified independent risk factors. Among 9646 donors, 87.80% were male (sex ratio 7.19), mostly aged 18–24 (55.93%), with students forming the largest group (58.67%). Mobile units collected 70.80% of donations; 52.60% were repeat donors. Overall TTVI seroprevalence was 9.35%, with HBV (6.29%) most common, followed by HCV (1.78%) and HIV (1.28%). Chi-square tests revealed significant associations between serostatus and donor status, donation site, and occupation, but not sex. Logistic regression identified independent risk factors: age, donor status, and donation site were significantly associated with HIV infection; male sex, older age, occupation, and donor status predicted HBV infection; and only donor status was significantly associated with HCV infection. These findings highlight the need for targeted recruitment and awareness strategies to improve transfusion safety. Full article

In the modern era of HIV treatment, people co-infected with HIV and HBV still face poor liver outcomes, including liver fibrosis, liver cirrhosis, and hepatocellular carcinoma. We investigated baseline characteristics and long-term liver function outcomes in 435 people living with HIV and HBV co-infection, focusing on HCC-associated point mutations (PMs) and PreS region deletion mutations. PMs were present in 72.9% of participants and were associated with male predominance, lower HBV genotype C prevalence, reduced HBV DNA and HBeAg levels, and higher HBsAg and HBeAb positivity. However, PMs did not significantly impact liver function or fibrosis progression over six years of ART follow-up. In contrast, PreS deletions were found in 21.8% of cases and stratified into PreS1, PreS2, and PreS1+2 deletions. PreS2 and PreS1+2 deletions were linked to older age, higher HBsAg and AFP levels, elevated liver enzymes, and lower platelet counts. These groups also exhibited significantly worse liver fibrosis markers (APRI and FIB-4), with PreS2 deletions consistently showing the highest values throughout the follow-up. Despite the initial improvement with ART, patients with PreS2 and PreS1+2 deletions maintained higher fibrosis and cirrhosis risks over six years. In summary, while PMs were not predictive of liver disease progression, PreS deletion mutations (especially in the PreS2 region) were associated with poorer liver outcomes, indicating their potential as biomarkers for fibrosis risk in co-infected individuals with long-term ART. Full article

In Nigeria, hepatitis B virus (HBV) infection remains a significant public health issue. The emergence of immune escape mutants (IEMs), basal core promoters, and precore (BCP/PC) mutants among asymptomatic individuals has enabled the continuous evolution of the virus in the country. In this study, we used Sanger sequencing of the S gene and the BCP/PC region to investigate the genetic diversity, phylogenetic relationships, and mutational profiles of HBV strains detected in two regions in Nigeria. A total of 178 HBsAg-positive samples confirmed by ELISA underwent viral DNA extraction and PCR amplification of the surface and BCP/PC genes, and 76 and 60 sequences were found to be exploitable for S and BCP/PC genes, respectively, which were used for HBV genotyping and mutational analysis. We detected various mutations in the major hydrophilic loop (target of neutralizing antibodies), including vaccine escape mutants (VEMs) (L127P/R, S140T/L, and G145A), HBV immunoglobulin resistance mutants (T131N, S143T, and W156R), and mutations previously reported in patients with reactivated infections (T115N, G159A/R, and F161Y). We also identified a high proportion of C1741T in 34/42 (81%) along with A1762T or G1764A mutation in 14/42 (33%) and 18/42 (43%) as the dominant variants in the BCP region. The predominant classical PC G1896A and G1899A variants were identified in 26/42 (62%) and 17/42 (40%) participants in this study. Two HBV genotypes were identified (A and E). However, HBV genotype E was the most frequently identified genotype, and is still the dominant strain circulating in Nigeria. We report the circulation of HBV IEMs and the preponderance of BCP and classical PC variants among asymptomatic carriers. Our findings suggest that the spread of these HBV mutant variants among asymptomatic carriers may have an impact on the effectiveness of diagnostic immunoassays and the success of HBsAg-based vaccinations. This highlights the need for robust surveillance. Full article

Hepatitis D virus (HDV) infection remains a major cause of severe liver disease among hepatitis B virus (HBV)-infected patients, contributing to accelerated progression to cirrhosis and hepatocellular carcinoma. Pegylated interferon-α remains the first-line therapy for chronic HDV infection in most cases. However, despite its approval for HBV and hepatitis C virus (HCV) infections, its use in HDV is largely driven by a lack of other options and is constrained by its limited efficacy, suboptimal durability of response, and a substantial side effect profile. Meanwhile, bulevirtide, an entry inhibitor, became the first agent to be approved for use in chronic HDV infections by the European Medicines Agency (EMA), and several other therapies are currently being investigated as well. In this review, we provide updates on recent advancements in HDV treatment and novel therapies. Full article

Background/Objectives: Glucan particles (GPs), derived from Saccharomyces cerevisiae yeast, possess unique biomedical properties. Nevertheless, it is imperative that a comprehensive risk assessment is conducted during pre-clinical development. GPs are primarily constituted of a naturally occurring polymer known as β-glucan. This study characterized GPs, focusing on physicochemical attributes, biocompatibility, and immunomodulatory potential. Methods: GPs were characterized for size, morphology, surface charge, and protein encapsulation efficiency using dynamic light scattering (DLS), electron microscopy, and encapsulation assays. Biocompatibility was assessed through cytotoxicity assays (MTT), hemolysis tests, and measurement of reactive oxygen (ROS) and nitric oxide (NO) production in immune cells. Immunomodulatory potential was evaluated by cytokine and chemokine secretion analysis in peripheral blood mononuclear cells (PBMCs) and monocyte-derived dendritic cells (moDCs) and through in vivo immunization studies in a murine model, focusing on cellular immune responses. Results: GPs demonstrated stable physicochemical properties and efficient protein encapsulation, highlighting their suitability as vaccine delivery systems. They exhibited biocompatibility by not inducing cytotoxicity, hemolysis, or excessive ROS and NO production. In PBMCs, GPs stimulated cytokine secretion, suggesting their adjuvant potential. GPs were efficiently internalized by monocytes and led to specific chemokine secretion in stimulated moDCs. In a murine model, GPs induced distinctive cellular immune responses, including TNF-α and IFN-γ production and effector memory T cell activation. Conclusions: These findings emphasize GPs’ biocompatibility and immunomodulatory effects, highlighting their potential in immunotherapy and vaccine development, particularly for targeting infectious agents like hepatitis B virus. Full article

Chronic infection with the hepatitis B virus (HBV) results in over 1 million deaths annually. Although currently licensed treatments, including pegylated interferon-α and nucleoside/nucleotide analogs, can inhibit viral replication, they rarely eradicate covalently closed circular DNA (cccDNA) reservoirs. Moreover, vaccination does not offer therapeutic benefit to already infected individuals or non-responders. Consequently, chronic infection is maintained by the persistence of cccDNA in infected hepatocytes. For this reason, novel therapeutic strategies that permanently inactivate cccDNA are a priority. Obligate heterodimeric transcription activator-like effector nucleases (TALENs) provide the precise gene-editing needed to disable cccDNA. To develop this strategy using a therapeutically relevant approach, TALEN-encoding mRNA targeting viral core and surface genes was synthesized using in vitro transcription with co-transcriptional capping. TALENs reduced hepatitis B surface antigen (HBsAg) by 80% in a liver-derived mammalian cell culture model of infection. In a stringent HBV transgenic murine model, a single dose of hepatotropic lipid nanoparticle-encapsulated TALEN mRNA lowered HBsAg by 63% and reduced viral particle equivalents by more than 99%, without evidence of toxicity. A surveyor assay demonstrated mean in vivo HBV DNA mutation rates of approximately 16% and 15% for Core and Surface TALENs, respectively. This study presents the first evidence of the therapeutic potential of TALEN-encoding mRNA to inactivate HBV replication permanently. Full article

Several natural products have been shown to display antiviral activity against the hepatitis B virus (HBV), among a number of other viruses. In a previous study, the hydro-alcoholic extracts (n = 66) of 31 species from the Venezuelan Amazonian rain forest were tested on the hepatoma cell line HepG2.2.15, which constitutively produces HBV. One of the species that exerted inhibitory activity on HBV replication was Senna silvestris. The aim of this study was the bioassay-guided purification of the ethanol fraction of leaves of S. silvestris, which displayed the most significant inhibitory activity against HBV. After solvent extraction and two rounds of reverse-phase HPLC purification, NMR analysis identified salsolinol as the compound that may exert the desired antiviral activity. The purified compound exerted inhibition of both HBV DNA and core HBV DNA. Pure salsolinol obtained from a commercial source also displayed anti-HBV DNA inhibition, with an approximate MIC value of 12 µM. Although salsolinol is widely used in Chinese traditional medicine to treat congestive heart failure, it has also been associated with Parkinson’s disease. More studies are warranted to analyze the effect of changes in its chemical conformation, searching for potent antiviral, perhaps dual agents against HBV and HIV, with reduced toxicity. Full article

Schizophrenia is a challenging multifactorial neuropsychiatric disease that involves interactions between genetic susceptibility and environmental insults. Increasing evidence implicates viral infections as significant environmental contributors, particularly during sensitive neurodevelopmental periods. This review synthesises current findings on the viral hypothesis of schizophrenia, encompassing a wide array of neurotropic viruses, including influenza viruses, herpesviruses (HSV-1 and 2, CMV, VZV, EBV, HHV-6 and 8), hepatitis B and C viruses, HIV, HERVs, HTLV, Zika virus, BoDV, coronaviruses (including SARS-CoV-2), and others. These pathogens can contribute to schizophrenia through mechanisms such as direct microinvasion, persistent central nervous system infection, immune-mediated neuroinflammation, molecular mimicry, and the disturbance of the blood–brain barrier. Prenatal exposure to viral infections can trigger maternal immune activation, resulting in cytokine-mediated alterations in the neurological development of the foetus that persist into adulthood. Genetic studies highlight the role of immune-related loci, including major histocompatibility complex polymorphisms, in modulating susceptibility to infection and neurodevelopmental outcomes. Clinical data also support the “mild encephalitis” hypothesis, suggesting that a subset of schizophrenia cases involve low-grade chronic neuroinflammation. Although antipsychotics have some immunomodulatory effects, adjunctive anti-inflammatory therapies show promise, particularly in treatment-resistant cases. Despite compelling associations, pathogen-specific links remain inconsistent, emphasising the need for longitudinal studies and integrative approaches such as viromics to unravel causal relationships. This review supports a “multi-hit” model in which viral infections interfere with hereditary and immunological susceptibilities, enhancing schizophrenia risk. Elucidating these virus–immune–brain interactions may facilitate the discovery of biomarkers, targeted prevention, and novel therapeutic strategies for schizophrenia. Full article

The precipitation of cryoglobulins, serum immunoglobulins, below 37 °C defines the clinical cryoglobulinemic syndrome, a systemic vasculitis usually characterized by purpura, weakness, and arthralgia. In most cases, this condition is associated with chronic infection by the hepatitis C virus (HCV) and can evolve into B-cell dysregulation and malignancies. The current literature on non-HCV-associated cryoglobulinemia is very limited, and little is known about the immunological and serological profile of affected patients. The cryoglobulinemic syndrome not associated with HCV infection is often found concomitantly with other infections, autoimmune diseases, and B-cell lymphoproliferative disorders. The cryoprecipitation of fibrinogen has been described as a rare disorder, perhaps underestimated and not fully understood, causing thrombotic occlusion and ischemia in different rheumatic disorders. Cold temperature plays a pathogenetic role in autoimmune hemolytic anemias, in which the presence of cold agglutinins produced by B cells at the lymphoplasmacytic cell stage may promote agglutination of red blood cells in the coldest parts of the circulation, even at mild room temperatures, undergoing hemolysis. Laboratory methods for the detection and quantification of cryoproteins are downright critical, and their concurrent detection is pivotal for the diagnosis. In this review, we summarize the clinical involvement of cryoglobulins, cryofibrinogen, and cold agglutinins in non-HCV autoimmune diseases, underlining the crucial steps of the most employed analytic methods. Full article