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Hepatitis B virus (HBV) still remains a major global public health problem. One-half to one-third of the total HBV infected people died due to late detection of HBV. Serological antigen and viral HBV detections can help in the diagnosis, referral, and treatment of HBV. Available methods for HBV detection mostly used bulky instruments. Miniaturization of devices for HBV detection has been started by narrowing down the size of the devices. Several methods have also been proposed to increase the selectivity and sensitivity of the miniaturized methods, such as sandwich recognition of the biomarkers and the use of nano- to micro-sized materials. This review presents recent HBV detections in the last two decades from laboratory-based instruments towards microfluidic paper-based analytical devices ( µ PADs) for point-of-care testing (POCT) purposes. Early and routine analysis to detect HBV as early as possible could be achieved by POCT, especially for areas with limited access to a central laboratory and/or medical facilities., Competing Interests: All authors declare that they have no conflicts of interest., (Copyright © 2021 Aulia A. Tyas et al.)

DNA analysis is essential for diagnosis and monitoring of many diseases. Conventional DNA testing is generally limited to the laboratory. Increasing access to relevant technologies can improve patient care and outcomes in both developed and developing regions. Here, we demonstrate direct DNA analysis in paper-based devices, uniquely enabled by ion concentration polarization at the interface of patterned nanoporous membranes in paper (paper-based ICP). Hepatitis B virus DNA targets in human serum are simultaneously preconcentrated, separated, and detected in a single 10 min operation. A limit of detection of 150 copies/mL is achieved without prior viral load amplification, sufficient for early diagnosis of hepatitis B. We clinically assess the DNA integrity of sperm cells in raw human semen samples. The percent DNA fragmentation results from the paper-based ICP devices strongly correlate (R(2) = 0.98) with the sperm chromatin structure assay. In all cases, agreement was 100% with respect to the clinical decision. Paper-based ICP can provide inexpensive and accessible advanced molecular diagnostics.

Here we show that a simple paper-based electrochemical sensor, fabricated by paper folding, is able to detect a 30-base nucleotide sequence characteristic of DNA from the hepatitis B virus (HBV) with a detection limit of 85 pM. This device is based on design principles we have reported previously for detecting proteins via a metalloimmunoassay. It has four desirable attributes. First, its design combines simple origami (paper folding) assembly, the open structure of a hollow-channel paper analytical device to accommodate micrometer-scale particles, and a convenient slip layer for timing incubation steps. Second, two stages of amplification are achieved: silver nanoparticle labels provide a maximum amplification factor of 250 000 and magnetic microbeads, which are mobile solid-phase supports for the capture probes, are concentrated at a detection electrode and provide an additional ∼25-fold amplification. Third, there are no enzymes or antibodies used in the assay, thereby increasing its speed, stability, and robustness. Fourth, only a single sample incubation step is required before detection is initiated.

A novel three-dimensional DNA-AuNPs network structure amplification strategy was employed to design a lateral flow biosensor by introducing streptavidin coated gold nanoparticles (Au-SA) in this paper. They act as amplification probes which aggregate numerous gold nanoparticles (AuNPs) on test line by forming a three-dimensional DNA-AuNPs network structure in the presence of target. Sensitive detection of nucleic acid with point-of-care analysis is significant for infectious agent, early diagnosis and treatment of genetic diseases. The use of these particles in rapid ultrasensitive point of care (POC) lateral flow assays lead to a linear range from 0.1pM to 250nM with a limit of detection of 0.01 pM without polymerase chain reaction (PCR). The proposed method could increase the sensitivity by 4 orders of magnitudes than traditional sandwich assays labeled with AuNPs. Furthermore, the assay owns good reproducibility and stability, which will prove practical diagnostic applications., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The 1981 Lancet paper by Beasley et al., "Hepatocellular carcinoma and hepatitis B virus. A prospective study of 22707 men in Taiwan" is a seminal publication that clearly demonstrated that chronic infection with hepatitis B virus (HBV), as measured by seropositivity for the hepatitis B surface antigen (HBsAg), preceded the development of hepatocellular carcinoma (HCC). In doing so, this study paved the way for liver cancer prevention efforts through the implementation of hepatitis B vaccination programs. In this commentary, we will describe the discovery of HBV, which led to the study by Beasley et al.; summarize the major findings of the Beasley paper and its implications; discuss the importance of well-designed cohort studies for prevention activities; and consider the ramifications of the Beasley study and the work that has followed since., (Published by Elsevier Ltd.)

The transmission of bloodborne viruses through transfusion remains a major blood supply-related safety concern, with hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) being the most important pathogens in this context. Real-time bioluminescent pyrophosphate testing has been developed as a means of readily detecting bacterial cells within particular sample types without requiring the use of expensive or complex instrumentation. The sensitivity of this approach, however, is often limited such that it is not compatible with many potential applications. In this study, we sought to overcome the limitations of this pyrophosphate bioluminescent assay format by using 2-deoxyadenosine-5-(α-thio)-triphosphate (dATPαS) in place of dATP for PCR amplification, thereby dramatically reducing background signal levels. We leveraged this combination PCR and bioluminescent pyrophosphate assay approach to facilitate HBV detection. This assay yielded a limit of detection of 500 copies/mL, making it more sensitive than traditional bioluminescent assays, about 1000 times more sensitive than that of PCR product analysis by agarose gel electrophoresis, and roughly as sensitive as qPCR as a means of detecting viral DNA. We then used this assay to analyze 100 serum samples, with qPCR being used for result validation. The assay required 100 min to complete, and was able to detect as few as 500 copies/mL of viral DNA. Overall, our approach was rapid, sensitive, and simple, enabling users to readily detect HBV in a reliable and efficient manner., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Hepatitis B and C virus, Opisthorchis viverrini and Clonorchis sinensis, are all individually known to put a person at increased risk for cholangiocarcinoma and hepatocellular carcinoma. This paper seeks to determine if there is any interaction between liver flukes and hepatitis virus infection that are known to put a person at an increased risk for cholangiocarcinoma and hepatocellular carcinoma collectively. This paper seeks to determine whether there is any publicly available articles in English that determine if having a hepatitis viral co-infection along with liver flukes would influence the risk of developing liver cancer. We followed PRISMA systematic review guidelines to conduct a literature review. Three manuscripts fit the search criteria. Two presented evidence in support of a synergistic relationship between liver fluke and viral hepatitis infection while the other found no relationship. One manuscript determined that the interaction between hepatitis B and C. sinensis did not have any significant risk of liver cancer. Studies found that HBV affected progression of co-infection to liver cancer but may have its own disease state worsened by presence of liver flukes. Only one paper was found that presented data on HCV, therefore no conclusion can be drawn due to the lack of evidence discovered. Of the studies, the conclusions and strength of the data were mixed. However, the stronger studies suggested a synergistic relationship between liver flukes and HBV to increase the risk of progressing to liver cancer. [ABSTRACT FROM AUTHOR]

Background: A protective hepatitis B virus (HBV) vaccine has been available for four decades. Universal HBV vaccination of infants is recommended by the WHO since the 1990s. Furthermore, HBV immunization is advised for all adults with high-risk behaviours and no seroprotection. However, HBV vaccine coverage remains globally suboptimal. The advent of new more efficacious trivalent HBV vaccines has renewed the interest in HBV vaccination. At present, the extent of current HBV susceptibility in adults remains unknown in Spain., Methods: HBV serological markers were assessed on a large and representative sample of adults in Spain, including blood donors and individuals belonging to high-risk groups. Serum HBsAg, anti-HBc and anti-HBs were tested in specimens collected during the last couple of years., Results: From 13 859 consecutive adults tested at seven cities across the Spanish geography, overall 166 (1.2%) had positive HBsAg. Past HBV infection was recognized in 14% and prior vaccine immunization in 24%. Unexpectedly, 37% of blood donors and 63% of persons belonging to high-risk groups had no serum HBV markers and therefore were potentially HBV susceptible., Conclusion: Roughly 60% of adults living in Spain seem to be HBV susceptible. Waning immunity might be more common than expected. Hence, HBV serological testing should be performed at least once in all adults regardless of risk exposures. HBV vaccine full courses or boosters should be administered to all adults lacking serological evidence of HBV protection., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Electrochemiluminescence (ECL) has been considered to have better performance in rapid detection. A novel paper-based ECL biosensing platform for hepatitis B surface antigen (HBsAg) detection was developed based on a simple paper discs, the flexible design of a machine and a circuit of the custom-made ECL device. Through the modified magnetic suspension sandwich immunoassay protocol, rapid and sensitive clinical HBsAg detection was realized on the developed platform. The platform was characterized using cyclic voltammetry (CV) and ECL methods and obtained a linear range of 34.2 pg/mL–34.2 ng/mL with a 34.2 pg/mL (3σ) detection limit. This paper-based ECL sandwich immunoassay showed high sensitivity and selectivity, acceptable reproducibility, fast analysis time and better performance than chemiluminescent immunoassay (CLIA) and enzyme-linked immunosorbent assay (ELISA) for detecting HBsAg in real clinical serum samples. [ABSTRACT FROM AUTHOR]

Background: In China, the vaccinated blood donors have rapidly increased by recent years, which may impact blood safety. The true prevalence of HBV between vaccinated blood donors and non-vaccinated blood donors should be explored., Study Design and Methods: The samples of blood donors were collected and detected for serologic markers of HBV in the Shenzhen Blood Centre (SZBC). The discrepant results were tested with commercial electrochemiluminescence immunoassay (ELCI) for HBsAg, anti-HBs, HBeAg, Anti-HBe and Anti-HBc, alternative MPX ID NAT, nested PCR, and a quantitative real-time polymerase chain reaction (qPCR) assay for HBV DNA. The serological and molecular characteristics of HBV infected blood donors were analysed, and the effects on blood safety for donors born before and after the implementation of universal HBV vaccination were compared., Results: Out of 242 presumed HBV infected donors from 26 318 donations, 131 (0.49%, [95% CI, 0.43-0.59]) chronic HBV infections (CHB, HBsAg detected with or without DNA), 58 (0.22%, [95% CI, 0.17-0.28]) occult hepatitis B infections (OBI, HBsAg not detected, assume anti-HBc positive and/or anti-HBs with HBV DNA) and 3 (0.011%, [95% CI, 0.0023-0.033]) window period (WP) infections were confirmed respectively. There were 28 CHBs (0.44%), 7 OBIs (0.11%) and 1 WP (0.016%) from vaccinated blood donor and 103 CHBs (0.52%), 51 OBIs (0.26%) and 2 WPs (0.01%) from non-vaccinated blood donor. The HBV+ (CHBs, OBIs and WPs) rate (0.56%) in vaccinated donors was lower than in non-vaccinated donors (0.78%, p < 0.05). The HBsAg titers of vaccinated infected blood donors (Median: 128.8 IU/ml) were much higher than non-vaccinated infected blood donors (58.4 IU/ml). The OBI yield rates in the vaccinated blood donors was significantly lower than the non-vaccinated blood donors (p < 0.05). There 102/124 (82.3%) samples were genotype B, 22/124 (17.7%) were genotype C respectively. There was no significant difference in the distribution of genotype between non-vaccinated blood donors (B/C, 86/17) and vaccinated blood donors (B/C, 23/6; p > 0.05). High frequency of vaccine escape mutations M133L (32.4%) and E164G in S region of genotype B strains and substitution L175S (40.9%) related to vaccine escape in S region of genotype C strains were identified., Conclusion: The universal HBV vaccination program markedly reduces the risk of HBV infection in blood donors, and provides a significant guarantee for the safety of blood transfusion. Several important mutations detected related vaccine escape and notable mutations needed further investigated., (© 2022 British Blood Transfusion Society.)

The conjugation of polysaccharides with an effective carrier protein is critical for the development of effective bacterial polysaccharide vaccines. Therefore, the identification and optimization of carrier proteins to induce an effective immune response is necessary for developing a combined vaccine. In the current study, we utilized hepatitis B virus surface antigen (HBsAg) as a novel carrier protein combined with a capsular polysaccharide molecule to develop a new pneumococcal conjugated vaccine. The specific antibodies and T cell immune response against the capsular polysaccharide and HBsAg in the mice immunized with this conjugated vaccine were evaluated. In addition, the unique gene profiles of immune cells induced by this conjugated vaccine in the immunized mice were analyzed. Our results demonstrated that the vaccine consisting of pneumonia type 33 F capsular polysaccharide (Pn33Fps) conjugated with HBsAg can induce strong specific immune responses against both antigens in vivo in immunized mice. Furthermore, the conjugated vaccine induced higher expression of genes related to the activation of immunity and higher antibody titers against Pn33Fps and HBsAg in mice than those obtained via vaccination with a single antigen. Analyses of the dynamic expression changes in immunity-related genes in mice immunized with Pn33Fps&#95;HBs, Pn33Fps, or HBsAg indicated the potent immunogenicity of the conjugated vaccine. In addition, a pathological evaluation of the organs from immunized mice further suggested that the conjugated vaccine is safe. Together, these results indicate that a conjugated vaccine consisting of Pn33Fps with HBsAg is a novel and effective vaccine.

Abstract This article presents the World Health Organization's (WHO) recommendations on the use of hepatitis B vaccines excerpted from the Hepatitis B vaccines: WHO position paper, July 2017 , published in the Weekly Epidemiological Record (Hepatitis B vaccines, 2017) [1]. This position paper replaces the May 2009 WHO position paper on hepatitis B vaccines (Hepatitis B vaccines, 2009) [2]. The position paper gives updated information on hepatitis B vaccines and their storage, transport and deployment. The recommendations concern the target groups for vaccination and the appropriate schedules. In particular, the recommendations stress the importance of vaccination of all infants at birth as the most effective intervention for the prevention of hepatitis B virus-associated disease worldwide. Footnotes to this paper provide a number of core references including references to grading tables that assess the quality of the scientific evidence, and to the evidence-to-recommendation table. In accordance with its mandate to provide guidance to Member States on health policy matters, WHO issues a series of regularly updated position papers on vaccines and combinations of vaccines against diseases that have an international public health impact. These papers are concerned primarily with the use of vaccines in large-scale immunization programmes; they summarize essential background information on diseases and vaccines, and conclude with WHO's current position on the use of vaccines in the global context. Recommendations on the use of hepatitis B vaccines were discussed by SAGE in October 2016; evidence presented at these meetings can be accessed at: http://www.who.int/immunization/sage/meetings/2016/October/presentations_background_docs/en/. [ABSTRACT FROM AUTHOR]

Hepatitis B virus reactivation (HBVr) is not uncommon in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Hepatitis B surface antigen (HBsAg)-positive patients receiving allo-HSCT have a very high risk of HBVr. However, the validity of prophylactic antiviral treatment in HBsAg-positive allo-HSCT recipients has not been well studied. We aimed to add experience in dealing with HBsAg-positive patients following allo-HSCT. We conducted a cohort study that included 11 years of data of HBsAg-positive allo-HSCT patients in multiple centers. The cumulative incidence of HBVr with antiviral prophylaxis at 60 months following transplantation was 8.9%. Both lamivudine (LAM) and entecavir (ETV) effectively reduced the incidence of HBVr. Patients with absent-mild cGVHD had a lower HBVr rate than that of patients with moderate-severe cGVHD (HR = 0.201, P = 0.020). The incidence of HBsAg seroclearance at 60 months following transplantation was 34.3%. Recipients accepting from anti-HBs-negative donors were associated with a lower HBsAg seroclearance rate than that of those accepting from anti-HBs-positive donors (HR=0.255, P < 0.001). The peripheral blood stem cell (PBSC) donor source had a higher HBsAg seroclearance rates than that of the PBSC plus bone marrow stem cell source (HR = 4.700, P = 0.047). The prophylactic antiviral treatment effectively reduced HBVr in HBsAg-positive recipients receiving allo-HSCT. HBsAg-positive recipients accept anti-HBs-positive PBSC donor sources may facilitate the acquisition of HBsAg seroclearance after transplantation., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Classical gold standard HBV detection relies on expensive devices and complicated procedures, thus is always restricted in large-scale hospitals and centers for disease control and prevention. To extend HBV detection to primary clinics especially in underdeveloped areas, we design amplification-free smartphone-based attomolar HBV detecting technique based on single molecule sensing. Verified by synthesized HBV target DNA, this technique reaches a detection limit at attomolar concentration (100 aM); and verified by 110 clinical samples, it also reaches a rather high sensitivity of 10 4 copy/mL (≈2000 IU/mL) with a high accuracy of 93.64% certificated by gold standard HBV detecting devices. Besides, this technique can quantify HBV viral load in 70 min only using portable and inexpensive devices as well as simple operations. Because of its cost-effective, field-portable and operable design, highly sensitive and selective detecting capability and wireless data connectivity, this technique can be potentially used in mobile HBV diagnoses and share HBV epidemic information especially in resource limited situations., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Electrochemical paper-based analytical devices (ePADs) are useful analytical devices that serve as point-of-care testing (POCT) devices for various clinical biomarkers in view of their simplicity, portability, and low-cost format. However, multistep reagent manipulation usually restricts the performance of the device for end users. Herein, we developed a sequential ePAD for sequential immunosensing fluid delivery by integrating dual flow behaviors (fast-flow/delayed) within a single paper platform for the simultaneous detection of hepatitis B surface antigen (HBsAg) and hepatitis C core antigen (HCVcAg). In the present work, a fast-flow channel was used for the automated washing of unbound antigens, while a delayed channel was created to store a redox reagent for further electrochemical analysis with a single buffer loading (the analysis time can be completed within 500 s). Hence, the undesirable complex procedure of multi-step reagent manipulation is scarcely needed by the user. The detection limit of the proposed ePAD was as low as 18.2 pg mL−1 for HBsAg and 1.19 pg mL−1 for HCVcAg. In addition, this proposed ePAD was also proven to be effective in real clinical sera from patients to verify its biological applicability. The ePAD sensor shows high promise as an easy-to-use, portable, and extendable sensor for other multiplex biological assays. [Display omitted] • ePAD for simultaneous HBsAg and HCVcAg was created. • First time employment of dual flow behaviors on ePAD for hepatitis markers sensing. • ePAD shows an easy to use, portability, and broad sensing applicability. • The sensor was applied to detect hepatitis markers in real clinical sera. [ABSTRACT FROM AUTHOR]

To ensure the safety of high-dose chemotherapy and autologous stem cell transplantation (HDC/ASCT), evidence-based recommendations on infectious complications after HDC/ASCT are given. This guideline not only focuses on patients with haematological malignancies but also addresses the specifics of HDC/ASCT patients with solid tumours or autoimmune disorders. In addition to HBV and HCV, HEV screening is nowadays mandatory prior to ASCT. For patients with HBs antigen and/or anti-HBc antibody positivity, HBV nucleic acid testing is strongly recommended for 6 months after HDC/ASCT or for the duration of a respective maintenance therapy. Prevention of VZV reactivation by vaccination is strongly recommended. Cotrimoxazole for the prevention of Pneumocystis jirovecii is supported. Invasive fungal diseases are less frequent after HDC/ASCT, therefore, primary systemic antifungal prophylaxis is not recommended. Data do not support a benefit of protective room ventilation e.g. HEPA filtration. Thus, AGIHO only supports this technique with marginal strength. Fluoroquinolone prophylaxis is recommended to prevent bacterial infections, although a survival advantage has not been demonstrated.

Due to a lack of standardized tests, it is difficult to obtain prevalence data and define the real impact of occult HBV infection (OBI) in Western countries. The present review article addresses the prevalence of OBI, defined as presence of hepatitis B virus (HBV) DNA in liver tissue or plasma in HBsAg-negative subjects, in Western countries. This varies in different studies according to the different methodologies used (based on serology vs virology), to the sample analyzed for the diagnosis (liver tissue vs plasma), to the different populations studied, to the different geographical variations in the HBV spread, to the host characteristics (age, gender, risk factors for acquiring HBV infection) and to the presence of other parenteral infections (hepatitis C virus and/or human immunodeficiency virus [HIV] infections). Considering the different liver diseases analyzed, that is in patients with cryptogenic cirrhosis or advanced liver fibrosis, the prevalence of OBI ranges 4% to 38%. Considering the different populations studied, in the case of parenteral blood exposure it is about 45%, in patients with chronic hepatitis C it is estimated at about 52%, in HIV-infected patients it ranges from 0% to 45%, in blood donors from 0% to 22.7% and in hemodialysis patients it ranges from 0% to 54%. In conclusion, OBI is a virological entity to be considered when performing the patient's evaluation for immunosuppressive diseases, liver pathologies, or for blood transfusions. Knowing the prevalence and clinical impact of OBI will allow better patient management., (© 2020 Wiley Periodicals LLC.)

Purpose: The mechanisms underlying HBV intrauterine transmission remain unknown. In this study, we explored the mechanism of HBV intrauterine transmission by iTRAQ proteomics analysis., Methods: iTRAQ technology was applied to perform comparative proteomics studies on six HBV +/+ neonates and six HBV +/-  neonates whose mothers and fathers were HBsAg positive and paternal HBsAg negative, respectively. The data obtained from the mass spectrometer were analyzed using MASCOT ( https://matrixscience.com ) to qualitatively and quantitatively compare the differentially expressed proteins in the two groups. Gene Ontology and KEGG pathway analyses were performed to analyze the differentially expressed proteins. The expressions of HBV intrauterine transmission-related proteins in serum samples and corresponding placental tissues were further verified by immunohistochemistry and Western Blot. Then, the human trophoblast cell line (Swan71) infected with HBV was used to analyze the potential mechanisms of HBV intrauterine transmission under the mediation of differential proteins., Results: A total of 35 differentially expressed proteins, including 17 up-regulated proteins and 18 down-regulated proteins, were identified by comparing serum protein expression levels in HBV +/+  and HBV +/-  neonates. The differentially expressed proteins were mainly related to RAGE receptor binding, NF-kappa B transcription factor activity, innate immune response, defense response to bacterium, and the signaling pathway in pathogenic microorganism infection. The expressions of S100A8/9/12 in HBV +/+ maternal placenta tissue were significantly increased. The expressions of S100A8/9/12 proteins in Swan71 cells were significantly increased after HBV infection., Conclusion: High expression of S100 proteins may be associated with the intrauterine-transplacental transmission of HBV.

The global burden of hepatitis B virus (HBV) is enormous, with 257 million persons chronically infected, resulting in more than 880,000 deaths per year worldwide. HBV exists as nine different genotypes, which differ in disease progression, natural history and response to therapy. HBV is an ancient virus, with the latest reports greatly expanding the host range of the Hepadnaviridae (to include fish and reptiles) and casting new light on the origins and evolution of this viral family. Although there is an effective preventive vaccine, there is no cure for chronic hepatitis B, largely owing to the persistence of a viral minichromosome that is not targeted by current therapies. HBV persistence is also facilitated through aberrant host immune responses, possibly due to the diverse intra-host viral populations that can respond to host-mounted and therapeutic selection pressures. This Review summarizes current knowledge on the influence of HBV diversity on disease progression and treatment response and the potential effect on new HBV therapies in the pipeline. The mechanisms by which HBV diversity can occur both within the individual host and at a population level are also discussed.

Background: Previous epidemiological studies suggest an association between hepatitis B virus (HBV) infection and B-cell non-Hodgkin lymphoma (B-NHL). The aim of our study was to evaluate clinical characteristics and serological indicators of HBV activity in patients who were diagnosed with both HBV infection and indolent or aggressive B-NHL., Methods: Seventy-two patients with current or resolved HBV infection and B-NHL were identified between 2000 and 2017 at our institution., Results: Forty-five (63%) and 27 (37%) patients were identified with aggressive and indolent B-NHL, respectively. In indolent B-NHL, the proportion of HBsAg-positive patients was significantly higher compared with aggressive B-NHL (59% vs 38%, P = .03). HBV-DNA levels were significantly higher in patients with indolent compared to aggressive B-NHL (P = .01). In the subgroup analyzes of follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL), the rate of HBsAg positivity in FL is significantly higher than that in DLBCL (83% vs 44%, P = .04), and HBV-DNA levels were significantly higher in FL compared with DLBCL (P = .007)., Conclusion: Our results suggest that serological HBV activity is higher in patients with both HBV infection and indolent B-NHL compared to those with aggressive B-NHL., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

• An electrochemical paper-based analytical device with pop-up structure is developed for hepatitis B virus DNA detection. • A Pop-up architecture enables a multi-step operation within a single device, ease of sample introduction, avoiding contamination and minimizing the exposure of biofluids. • A pyrrolidinyl peptide nucleic acid offers a higher binding affinity and specificity toward a complementary DNA over conventional DNA or PNA probe. • A low detection limit of 1 pM is allowed with a label-free system. • The feasibility of the proposed sensor with plasmid construct is achieved. Hepatitis B virus (HBV) is a chronic viral infection, causing significant health concerns worldwide. For point-of-care testing, a simple, rapid, and disposable sensor is required. In this work, a pop-up DNA device as an alternative 3D microfluidic paper-based analytical device (μPAD) platform was firstly proposed for label-free HBV DNA detection. The pop-up design was created to allow control of the fluidic path, incubation time, and electrical connectivity by simple folding. The proposed platform enabled a multi-step operation to be performed within a single device. Moreover, this architecture allows facile sample introduction, avoiding contamination and minimizing the exposure of biofluids. A pyrrolidinyl peptide nucleic acid, acpcPNA, which exhibits high affinity and selectivity, was covalently immobilized onto the modified cellulose on a working electrode for capturing the target DNA. Differential pulse voltammetry was employed with a signal-off system. The presence of HBV DNA resulted in a decrease of the electrochemical signal of hexacyanoferrate (III)/(II) in a concentration-dependent fashion. Under optimal conditions, a linear range of 50 pM-100 nM with the detection limit of 1.45 pM was achieved. Moreover, good selectivity of proposed device was demonstrated. The pop-up DNA sensor was successfully applied for the detection of HBV DNA extracted from plasmid constructs. [ABSTRACT FROM AUTHOR]

Introduction: Patients with resolved hepatitis B virus infection undergoing rituximab are at risk of hepatitis B virus reactivation without antiviral prophylaxis. However, the risk in such patients treated with rituximab-based regimens for membranous nephropathy is not clear. We evaluated the risk of hepatitis B virus reactivation in membranous nephropathy patients with resolved infection undergoing rituximab-based regimens without antiviral prophylaxis., Methods: Clinical data of 51 membranous nephropathy patients with resolved hepatitis B virus infection undergoing rituximab-based regimens without antiviral prophylaxis were retrospectively analyzed. Among these, 21 patients were followed for more than 1 year after rituximab discontinuation. The clinical data collected aimed to assess patients' responses and the risk of hepatitis B virus reactivation during and after rituximab treatment., Results: 30/51 (58.8 %) patients reached complete or partial remission at 12 months. None of the patients experienced HBsAg seroreversion during rituximab treatment. Alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase and total bilirubin levels, as well as the numbers of patients who exceeded the upper limits of normal for alkaline phosphatase and prothrombin time, did not show any statistically significant difference during rituximab-based therapy. Neither did the anti-HBs level, the number of patients with protective anti-HBs titers exceeding 10 U/L, nor the levels of CD19+ B cells, CD4+ T cells, CD8+ T cells, and natural killer cells. Among the 21 patients followed for 12 (ranging from 12 to 19) months after rituximab discontinuation, no hepatitis B virus reactivation was observed. The mean anti-HBs level and the number of patients with anti-HBs titers over 10 U/L did not show any statistically significant difference during the extended follow-up of 33 patient-years. Neither did the CD4+ T cell, CD8+ T cell, nor the natural killer cell counts. One patient presented with an ALT level that exceeded the baseline value by three times and reached above 100 U/L, accompanied by elevations in AST, GGT, and ALP levels. Meanwhile, the anti-HBs titer was 816.09 U/L, and HBsAg was negative., Conclusion: The administration of rituximab-based regimens in membranous nephropathy patients with hepatitis B virus resolved infection leads to a low risk of hepatitis B virus reactivation without antiviral prophylaxis. Patient's immune status, drug combination, rituximab strategy should be fully evaluated when considering antiviral prophylaxis therapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Bispecific antibodies (bsAbs) are engineered immunoglobulins that combine two different antigen-binding sites in one molecule. BsAbs can be divided into two molecular formats: IgG-like and non-IgG-like antibodies. Structural elements of each format have implications for engaging the immune system. T cell engager antibodies (TCEs) are bsAbs designed to engage T cells with target cells. TCEs can be applied not only in cancer but also in infectious disease therapy to activate T-cell responses. In this review, we focus on current literature on the design and use of bsAbs as an innovative strategy to enhance adaptive antiviral immune responses. We summarized the novel T cell-related immunotherapies with a focus on TCEs, that are developed for the treatment of chronic hepatitis B. Chronic infection with the hepatitis B virus (HBV) had a death toll of 1.1 million humans in 2022, mainly due to liver cirrhosis and hepatocellular carcinoma developing in the more than 250 million humans chronically infected. A curative treatment approach for chronic hepatitis B is lacking. Combining antiviral therapy with immune therapies activating T-cell responses is regarded as the most promising therapeutic approach to curing HBV and preventing the sequelae of chronic infection. Attracting functionally intact T cells that are not HBV-specific and, therefore, have not yet been exposed to regulatory mechanisms and activating those at the target site in the liver is a very interesting therapeutic approach that could be achieved by TCEs. Thus, TCEs redirecting T cells toward HBV-positive cells represent a promising strategy for treating chronic hepatitis B and HBV-associated hepatocellular carcinoma., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Hepatitis B virus (HBV) exhibits high prevalence rates within Ethiopia. The genetic diversity of HBV, marked by mixed genotype infections, may hold significant implications for the trajectory of disease and responses to treatment. Ethiopia grapples with a substantial public health challenge posed by co-infections involving HBV, hepatitis C virus (HCV), and human immunodeficiency virus 1 (HIV-1), particularly among vulnerable populations., Methods: A comprehensive investigation into HBV, HCV, and HIV-1 co-infection was conducted. A total of 7,789 blood samples were meticulously analyzed, among which 815 exhibited HBV positivity. Among the HBV-positive samples, 630 were subjected to genotyping procedures, resulting in the identification of a prevalent trend of mixed infections characterized by HBV genotypes A/E/F (67.30%). Serological assessments were performed on 492 specimens to ascertain the presence of HCV and HIV-1 co-infections, revealing respective co-infection rates of 13.02% for HBV/HIV, 3.31% for HBV/HCV, and 2.07% for triple infection., Results: The investigation revealed the intricate prevalence of co-infections in Ethiopia, notably underlining the continued transmission of viruses. The prominent occurrence of mixed HBV genotypes A/E/F suggests dynamic viral interactions and ongoing transmission pathways. These findings accentuate the necessity for targeted interventions and enhanced patient care, as co-infections carry significant clinical complexities., Conclusions: This study furnishes crucial insights into the molecular epidemiology of HBV, HCV, and HIV-1 co-infections in Ethiopia. The acquired knowledge can contribute to the advancement of strategies for clinical management and the formulation of public health interventions aimed at ameliorating the burden of viral infections within the nation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Cytokines may related to intrauterine Hepatitis B virus (HBV) transmission. 205 HBsAg(+) pregnant cases and 74 HBsAg(-) women were included. Neonatal blood samples were taken within 24 h of delivery and before HBV vaccinations. Serological HBV biomarkers and cytokines were detected. 21.9 % of the newborns from HBsAg(+) women were intrauterinally transmitted, including 7.3 % with dominant transmission (DBT) and 14.6 % occult transmission (OBT). HBV DNA load (odd ratio [OR], 1.44; 95 % confidence interval [CI], 1.05-1.98), interferon-γ (IFN-γ) (OR, 1.01; 95 %CI, 1.00-1.02) and toll-like receptor 9 (TLR9) (OR, 1.27; 95 %CI, 1.06-1.52) positively correlated with DBT. Only IFN-γ (OR, 1.01; 95 %CI, 1.00-1.01) positively associated with OBT. According to the generated restricted cubic spline, TLR9 was positively correlates with rise of DBT in a log-shape. It may be possible to develop a nomogram which intercalates these factors to predict intrauterine HBV transmissions. Further research should consider immune processes involved in chorioamnionitis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

High levels of hepatitis B virus (HBV) surface antigen (HBsAg) in the blood of chronic HBV carriers are considered to drive the exhaustion of antigen-specific T and B lymphocytes and thus responsible for the persistence of infection. Accordingly, therapeutic elimination of HBsAg may facilitate the activation of adaptive antiviral immune responses against HBV and achieve a functional cure of chronic hepatitis B. We discovered recently that an amphipathic alpha helix spanning W156 to R169 of HBV small envelope (S) protein plays an essential role in the morphogenesis of subviral particles (SVPs) and metabolism of S protein. We thus hypothesized that pharmacological disruption of SVP morphogenesis may induce intracellular degradation of S protein and reduce HBsAg secretion. To identify inhibitors of SVP biogenesis, we screened 4417 bioactive compounds with a HepG2-derived cell line expressing HBV S protein and efficiently secreting small spherical SVPs. The screen identified 24 compounds that reduced intracellular SVPs and secreted HBsAg in a concentration-dependent manner. However, 18 of those compounds inhibited the secretion of HBsAg and HBeAg in HBV replicon transfected HepG2 cells at similar efficiency, suggesting each of those compounds may disrupt a common cellular function required for the synthesis and/or secretion of these viral proteins. Interestingly, lycorine more efficiently inhibited the secretion of HBsAg in HepG2 cells transfected with HBV replicons, HepG2.2.15 cells and HBV infected - HepG2 cells expressing sodium taurocholate cotransporting polypeptide (NTCP). The structure activity relationship and antiviral mechanism of lycorine against HBV have been determined., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

We aimed to compare the NeuMoDx HBV Assay with the artus HBV Assay using residual plasma samples and to evaluate the discordant results. The study included 200 patient samples analyzed with the NMD assay and stored at -80 °C. Samples were analyzed by artus in 2023. Discordant results were evaluated by cobas 6800 HBV DNA Test. Excellent agreement was found between both tests. Of the 100 samples that were HBV DNA negative by NMD, 93 were negative and 7 were positive by artus. With the Cobas test, 5 samples were positive. Of the100 HBV DNA positive samples detected by NMD, 99 were positive with the artus assay. This sample was also HBV DNA negative by the Cobas test. The sensitivity and specificity of NeuMoDx were found 93 % and 99 %, respectively. There was excellent qualitative agreement and strong quantitative correlation between the NeuMoDx and artus assays for HBV DNA detection and quantitation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Africa exhibits a considerably high prevalence of the hepatitis B virus among pregnant women. Furthermore, there is a discernible lack of a well-established surveillance system to adequately monitor and comprehend the epidemiology of the hepatitis B virus, particularly among pregnant women. The eradication efforts of the virus in Africa have been impeded by the significant disease burden in the region, and there is a lack of evidence regarding the pooled prevalence of the hepatitis B virus in Africa. Consequently, this systematic review and meta-analysis aims to determine the prevalence of hepatitis B virus infection among pregnant women in Africa., Methods: We conducted a systematic literature search using reputable databases such as PubMed, Advanced Google Scholar, Scopus, and the Cochrane Library. The search spanned from July 2013 to July 2023 and included all relevant articles published within this period. To identify potentially eligible articles, we conducted a comprehensive manual review of the reference lists of the identified studies. Our review encompassed articles from the African Journal Online. The analysis focused on observational studies published in peer-reviewed journals that reported the prevalence of hepatitis B surface antigen-positive testing among pregnant women. We utilized the Newcastle-Ottawa critical appraisal checklist to assess the methodological quality of each paper. Finally, a meta-analysis was conducted using a random-effects model., Results: Out of the 774 studies identified, 31 studies involving 33,967 pregnant women were selected for the meta-analysis. According to the random-effects model, the combined prevalence of hepatitis B virus among pregnant women was 6.77% [95% CI: 5.72, 7.83]. The I2 statistic was calculated to be 95.57% (p = 0.00), indicating significant heterogeneity among the studies. The high I2 value of 95.57% suggests a substantial degree of heterogeneity. A subgroup meta-analysis revealed that factors such as time-dependent bias, sample size dependence, or individual variation among study participants contributed to this heterogeneity (p-difference < 0.05)., Conclusion: According to the findings of this study, the pooled prevalence of hepatitis B infection among pregnant women in Africa was found to be intermediate-high. It is recommended that policymakers implement hepatitis B virus immunization programs targeting pregnant women and their new-born babies at higher risk of exposure., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Larebo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)