Search Results (257)

Background/Objectives: Hepatitis B virus (HBV) remains a persistent challenge for transfusion safety. Although testing for hepatitis B surface antigen (HBsAg) and nucleic acid testing (NAT) reduces transmission risk, antibodies to hepatitis B core antigen (anti-HBc) and antibodies to hepatitis B surface antigen (anti-HBs) provide additional insight into past infection and vaccine-induced immunity. We aimed to determine their seroprevalence among blood donors in southern Croatia and assess associations with age, occupation, and time since vaccination. Methods: This cross-sectional study was conducted between February and November 2024 at two regional transfusion centers in southern Croatia. A total of 1008 voluntary blood donors, all HBsAg- and NAT-negative, were tested for anti-HBc and anti-HBs using chemiluminescent microparticle immunoassay. Demographic and vaccination data were collected through verified medical records. Results: Anti-HBc was detected in 0.5% of donors, exclusively among the unvaccinated. Protective anti-HBs levels were found in 38.1% overall and 70.6% of vaccinated donors, with significant declines by age and more than 15 years post-vaccination (p = 0.024). Healthcare workers showed higher seroprotection than non-healthcare donors (67.0% vs. 35.1%; p < 0.001), although one-third still lacked protective levels. Conclusions: HBV exposure was rare, but waning vaccine-induced immunity was evident, with protective anti-HBs levels in 70.6% of vaccinated donors, declining with age and time since vaccination. These findings highlight the need for periodic monitoring of anti-HBs and targeted booster strategies, especially in older and occupationally exposed groups. HBsAg and NAT provide a high level of transfusion safety, while the role of routine anti-HBc testing in this low-endemic context should be carefully evaluated in view of its potential benefits and drawbacks. Donor-based surveillance is a valuable tool for evaluating long-term vaccine effectiveness and guiding public health policy. Full article

Chronic hepatitis B virus (HBV) infection remains a major global health challenge, substantially contributing to liver-related morbidity and mortality. Background/Objectives: Developing therapeutic strategies that overcome immune tolerance and achieve functional cures is an urgent priority. Methods: In this study, we report a therapeutic vaccine comprising hepatitis B surface antigen (HBsAg) formulated with the dual adjuvant system CpG 1018S and QS-21. The immunogenicity and therapeutic efficacy of this vaccine were systematically evaluated in an rAAV8-HBV1.3-established chronic HBV mouse model. Results: The vaccine elicited a robust Th1-skewed immune response, characterized by elevated anti-HBs IgG2b titers and an increased IgG2b/IgG1 ratio. Notably, immunized mice showed markedly reduced circulating HBsAg levels. Mechanistically, the CpG 1018S and QS-21 adjuvant system enhanced dendritic cell activation, maturation, and antigen presentation, expanded HBV-specific CD4⁺ and CD8⁺ T cell populations, and attenuated the expression of the exhaustion markers TIM-3 and TIGIT. Additionally, immunized mice exhibited restored T cell polyfunctionality, with an increased secretion of effector cytokines, including TNF-α and IL-21. These responses collectively contributed to the reversal of T cell exhaustion and breakdown of immune tolerance, facilitating sustained viral suppression. Conclusions: Our findings demonstrate that the CpG 1018S/QS-21-adjuvanted vaccine induces potent humoral and cellular immunity against chronic HBV infection and represents a promising candidate for clinical chronic HBV (CHB) treatment. Full article

The burden of hepatitis delta virus (HDV) infection is currently unknown and may affect 12 to 72 million people distributed across various hot spots in different regions of the globe. Screening for antibodies to HDV infection in patients positive for the hepatitis B surface antigen (HBsAg) is generally available in most parts of the world, but systematic testing for HDV is needed. Chronic HDV infection is associated with a higher risk of progression to cirrhosis, liver failure, and hepatocellular carcinoma compared to hepatitis B virus (HBV) mono-infection. Bulevirtide is the recently available treatment against hepatitis delta. The results of efficacy studies and new drugs (lonafarnib) are under discussion. New therapeutic strategies are in development, revealing a critical need for valid next-generation treatments to cure HDV. 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/Objectives: As a noninvasive indicator of liver fibrosis and stiffness, liver stiffness measurement (LSM) has also shown significant value in differentiating focal liver lesions (FLLs). This study aimed to assess the characteristics of LSM values across different liver lesions and explore their value in differential diagnosis. Methods: A total of 8817 individuals with FLLs were assessed using liver stiffness measurements (LSMs). We evaluated the LSM characteristics across different FLL categories and further compared these values within subgroups based on their alpha-fetoprotein (AFP) and hepatitis B surface antigen (HBsAg). The LSM was visualized graphically. We compared two logistic regression models (with the LSM and without the LSM) in a cohort of 2271 patients who were both AFP-normal (<20 ng/mL) and HBsAg-negative. The differentiation value of the LSM was quantified by comparing the models’ area under the curves (AUCs) and through decision curve analysis (DCA). Results: The LSM showed significant differences (p < 0.001) among malignant lesions, benign lesions, and cirrhotic nodules (CN). Among benign lesions, only focal nodular hyperplasia (FNH) and simple hepatic cysts (SHC) showed a significant difference (p < 0.05). Among malignant lesions, significant differences in the LSM were observed between all pairs (p < 0.001) except between hepatocellular carcinoma (HCC) and combined hepatocellular-cholangiocarcinoma (cHCC-CC). Patients with elevated AFP levels exhibited significantly higher LSM across most lesion types. HBsAg-positive patients also showed significantly increased LSM in all five lesion types, except for CN and cHCC-CC. The full model (with LSM) for differentiating primary malignant lesions from benign ones was built using six variables. The AUCs of the full model were 0.897 and 0.896 in the training and validation sets, significantly outperforming the comparison model (AUC: 0.882, p = 0.0002; 0.879, p = 0.017). Conclusions: The LSM can provide additional information on focal liver lesions. 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

Background: The 2022 conflict in Ukraine triggered mass migration, leading to a significant influx of Ukrainian refugee children into Poland. This situation raises concerns about hepatitis B virus immunity, as Ukraine’s hepatitis B vaccination coverage has been inconsistent compared to Poland’s high vaccination rates. Objective: To evaluate hepatitis B immunity and infection prevalence among Ukrainian refugee children residing in Southern Poland and to assess implications for vaccination strategies in the host country. Methods: A prospective cross-sectional study was conducted on 1322 Ukrainian refugee children (0–18 years) presenting to a pediatric infectious diseases department in Southern Poland between February 2022 and March 2024. Data on vaccination history, demographic characteristics, and selected laboratory parameters, including hepatitis B surface antigen and anti-HBs antibody levels, were collected. Protective immunity was defined as anti-HBs antibody levels ≥10 IU/L. Results: Among the participants (mean age 9.9 years; 50.2% female), 83.2% were reported as vaccinated according to national immunization programs, but only 64.9% demonstrated protective anti-HBs antibody levels. Protective antibody prevalence declined significantly with age, with less than half of adolescents aged 15–18 years showing immunity. Five children (0.4%) were diagnosed with chronic hepatitis B, four of whom were unvaccinated. Conclusions: This study identifies a significant gap in hepatitis B immunity among Ukrainian adolescent refugees residing in Southern Poland, with less than half possessing protective anti-HBs antibody levels. This immunity gap and the high risk of sexual transmission of the hepatitis B virus in adolescents highlight the urgent need for comprehensive surveillance, screening, and catch-up vaccination programs. Full article

A young adult patient presented to the gastrointestinal outpatient department with a suspected hepatic tumor. The patient was in a traffic accident ten years ago and underwent splenectomy and distal pancreatectomy at another medical institution. The physical examination was unremarkable. The liver function tests and tumor markers were within normal limits, with the alpha-fetoprotein level at 1.38 ng/mL. Both hepatitis B surface antigen and anti-HCV were negative. Based on the clinical history, intrahepatic splenosis was suspected first. Dynamic computed tomography revealed a 2.3 cm lesion exhibiting suspicious early wash-in and early wash-out enhancement patterns. As previous studies have reported, this finding makes hepatocellular carcinoma and metastatic lesions the major differential diagnoses. For further evaluation, dynamic magnetic resonance imaging was performed, and similar enhancing features were observed, along with restricted diffusion. As hepatocellular carcinoma still could not be confidently ruled out, the patient underwent an ultrasound-guided biopsy. The diagnosis of intrahepatic splenosis was confirmed by the pathologic examination. Intrahepatic splenosis is a rare condition defined as an acquired autoimplantation of splenic tissue within the hepatic parenchyma. Diagnosis can be challenging due to its ability to mimic liver tumors in imaging studies. Therefore, in patients with a history of splenic trauma and/or splenectomy, a high index of suspicion and awareness is crucial for accurate diagnosis and for prevention of unnecessary surgeries or interventions. Full article

Hepatitis B is a serious infectious disease that threatens the health of all mankind. In this study, we isolated and extracted hydroxytyrosol from Lindernia ruellioides with anti-hepatitis B virus (HBV) activity. The structure of hydroxytyrosol was identified by the nuclear magnetic resonance technique. HepG2.2.15 cell models were used to detect the anti-HBV activity and liver protection of hydroxytyrosol in vitro. Hydroxytyrosol can inhibit hepatitis B surface antigen (HBsAg) and hepatitis B e-antigen (HBeAg). The IC₅₀ values of HBsAg and HBeAg were 4.02 mg/L and 5.19 mg/L, respectively. At the highest concentration of hydroxytyrosol, the inhibition rates of supernatant and intracellular HBV DNA were 75.99% and 66.33%, respectively. Hydroxytyrosol was less toxic to normal human hepatocytes. Molecular docking showed that hydroxytyrosol was bound to three amino acid residues of HBV polymerase with a binding energy of −7.0 kcal/mol. This study provided data for the development and utilization of Lindernia ruellioides and the research and development of anti-hepatitis B virus drugs. Full article

Background: Hepatitis B virus (HBV) is a major cause of morbidity and mortality globally, and chronic infections are associated with cirrhosis and hepatocellular carcinoma. Issues with conventional treatments and vaccines mean there is a need for new therapeutic vaccines, which must elicit a strong and sustainable immune response. Here, we evaluated the immunogenicity of dual-antigen vaccines containing hybrid surface (hy-LHBs) and core (HBc) antigens, combined with a carboxyl-vinyl polymer (CVP) as a mucoadhesive excipient, following intranasal administration in mice. Methods: Mice were intranasally administered a mixed vaccine (10 µg of hy-LHBs and 2.5 or 10 µg of HBc) with or without a CVP excipient, and they were assessed for their immune response (levels of IgGs or IgA antibodies in an ELISA, IFN-γ level in splenocytes in an ELISpot assay, and cytokine/chemokine levels in a BioPlex assay). A protein stability assay was also conducted for vaccine formulations with and without excipients. Results: Significantly enhanced IgG production was noted targeting hy-LHBs and (less markedly) HBc at 10 µg/antigen, but only a non-significant elevation was noted with the vaccine containing 2.5 µg HBc. The BioPlex assay showed a significant increase in IL-2 (#00-07, 0B), IL-12(p40)(#00), eotaxin (#00), MIP1α (#00, #00-07, 0B), and MCP-1 (#00-07, 0B) in mice that received treatment compared to those of untreated mice. The endpoint titers of IgG1 and IgG2a were measured, which were higher with CVP excipients than without. From the IgG2a/IgG1 ratio, a higher IgG1 response was induced by CVPs to hy-LHBs and a higher IgG2a response was induced to HBc. Th2-dominant phenotype to hy-LHBs was induced with CVP#00 in an ELISpot assay. The highest anti-hy-LHBs antibody titer was noted with the conventional CVP#00 excipient. Consistent with these results, a higher amount of neutralizing antibodies of HBV was induced with CVP#00 treatment and followed by #00-03 and #14-00. Conclusions: We consider that the addition of CVP excipients to vaccine formulation enhances immunogenicity and HBV antigen stability for intranasal vaccines. This effect was seen for both humoral and cell-mediated immune responses, indicating the potential of CVPs as excipients in intranasal HBV vaccines. Full article

Chronic hepatitis B is linked with considerable liver-related morbidity and mortality globally. Human leukocyte antigen (HLA) polymorphisms affect the susceptibility and outcome of many immune-mediated diseases and infections. Our aim was to study the impact of HLA alleles on HVB-infected individuals in a Greek population. In total, 107 patients with chronic HBV infection (cHBV group) and 101 with spontaneous clearance (SC-group) of hepatitis B surface antigen (HBsAg) were genotyped for HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 loci by single-specific primer polymerase chain reaction (PCR-SSP). The HLA alleles’ frequencies were compared between the two patient groups and healthy individuals from the North Greece Bone Marrow Donor Registry (14506 samples). We found a significantly increased frequency of HLA-C*01 and HLA-DRB1*16 alleles in the cHBV group versus the SC-group. The frequency of HLA-A*01, HLA-B*08, HLA-C*01, HLA-C*08, HLA-DRB1*03, and HLA-DQB1*05 alleles was significantly higher in cHBV patients versus healthy individuals, while the frequency of the HLA-B*38 allele was significantly lower. Our study showed an association of specific HLA alleles with either susceptibility or protection against chronic HBV infection. Full article

Hepatitis B virus (HBV) is an important global public health issue. The World Health Organization (WHO) 2024 Global Hepatitis Report estimated that the global prevalence of people living with HBV infection is 254 million, with an estimated prevalence incidence of 1.2 million new HBV infections yearly. Previous studies have shown that natural compounds have antiviral inhibition potentials. In silico methods such as molecular docking, virtual screening, pharmacophore modeling, quantitative structure–activity relationship (QSAR), and molecular dynamic simulations have been successfully applied in identifying bioactive compounds with strong binding energies in HBV treatment targets. The COVID-19 pandemic necessitated the importance of repurposing already approved drugs using in silico methods. This study is aimed at unveiling the benefits of in silico techniques as a potential alternative in natural compounds’ drug discovery and repurposing for HBV therapy. Relevant articles from PubMed, Google Scholar, and Web of Science were retrieved and analyzed. Furthermore, this study comprehensively reviewed the literature containing identified bioactive compounds with strong inhibition of essential HBV proteins. Notably, hesperidin, quercetin, kaempferol, myricetin, and flavonoids have shown strong binding energies for hepatitis B surface antigen (HBsAg). The investigation reveals that in silico drug discovery methods offer an understanding of the mechanisms of action, reveal previously overlooked viral targets (including PreS1 Domain of HBsAg and cccDNA (Covalently Closed Circular DNA) regulators, and facilitate the creation of specific inhibitors. The integration of in silico, in vitro, and in vivo techniques is essential for the discovery of new drugs for HBV therapy. The insights further highlight the importance of natural compounds and in silico methods as targets in drug discovery for HBV therapy. Moreover, the combination of natural compounds, an in silico approach, and drug repurposing improves the chances of personalized and precision medicine in HBV treatment. Therefore, we recommend drug repurposing strategies that combine in vitro, in vivo, and in silico approaches to facilitate the discovery of effective HBV drugs. Full article

Background: This study aims to analyze the vaccination status and factors influencing delayed vaccination among toddlers born to hepatitis B surface antigen (HBsAg)-positive mothers. Methods: Data of HBsAg-positive mothers between 1 January 2021 and 31 December 2022 were provided by the Suzhou Maternal and Child Health Care and Family Planning Service Center. The vaccination records were obtained from the Jiangsu Province Immunization Service Management Information System. Logistic regression analysis was used to analyze influencing factors of delayed vaccination. Results: A total of 4250 toddlers born to HBsAg-positive mothers were documented. The data revealed that the first dose of the hepatitis B vaccine was administered to 100% of the toddlers. In addition, the coverage of the National Immunization Program (NIP) vaccines among these toddlers ranged from 92.9% to 99.4%. The proportion of delayed NIP vaccination varied between 0% and 12.2%. The proportion of delayed Bacillus Calmette–Guérin (BCG) vaccination was 11.3%, with the delay predominantly observed between 4 and 6 months. Notably, the proportion of delayed BCG vaccination among the toddlers born to HBsAg-positive mothers was significantly higher than that in the general population. Additionally, the proportion of the first dose of non-NIP vaccines was 3.3–36.4%, and the proportion of DTaP-IPV/Hib was 27.0%. Logistic regression analysis revealed that the regional level, the mother’s human papillomavirus (HPV) vaccination status, and the infant’s birth weight were significant factors influencing the timeliness of vaccination. Conclusions: Although the vaccination status of toddlers born to HBsAg-positive mothers in Suzhou city remains stable, the issue of delayed vaccination requires attention. It is essential to continue strengthening targeted vaccine education to reduce vaccine hesitancy and improve the rate of timely vaccination. Full article

Hepatitis, most importantly hepatitis B and hepatitis C, is a significant global health concern, requiring an accurate and early diagnosis to prevent severe liver damage and ensure effective treatment. The currently employed diagnostic methods, while effective, are often limited in their sensitivity, specificity, and rapidity, and the quest for improved diagnostic tools is ongoing. This review explores the innovative application of Raman spectroscopy combined with a chemometric analysis as a powerful diagnostic tool for hepatitis. Raman spectroscopy offers a non-invasive, rapid, and detailed molecular fingerprint of biological samples, while chemometric techniques enhance the interpretation of complex spectral data, enabling precise differentiation between healthy and diseased states and moreover the severity/stage of disease. This review aims to provide a comprehensive overview of the current research, foster greater understanding, and stimulate further innovations in this burgeoning field. The Raman spectrum of blood plasma or serum provides fingerprints of biochemical changes in the blood profile and the occurrence of disease simultaneously, while Raman analyses of polymerase chain reaction/hybridization chain reaction (PCR/HCR)-amplified nucleic acids and extracted DNA/RNA as the test samples provide more accurate differentiation between healthy and diseased states. Chemometric tools enhance the diagnostic efficiency and allow for quantification of the viral loads, indicating the stage of disease. The incorporation of different methodologies like surface enhancement and centrifugal filtration using membranes provides the ability to target biochemical changes directly linked with the disease. Immunoassays and biosensors based on Raman spectroscopy offer accurate quantitative detection of viral antigens or the immune response in the body (antibodies). Microfluidic devices enhance the speed of detection through the continuous testing of flowing samples. Raman diagnostic studies with massive sample sizes of up to 1000 and multiple reports of achieving a greater than 90% differentiation accuracy, sensitivity, and specificity using advanced multivariate data analysis tools indicate that Raman spectroscopy is a promising tool for hepatitis detection. Its reproducibility and the identification of unique reference spectral features for each hepatic disease are still challenges in the translation of Raman spectroscopy as a clinical tool, however. The development of databases for automated comparison and the incorporation of automated chemometric processors into Raman diagnostic tools could pave the way for their clinical translation in the near future. Full article