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Objective To establish a sort of direct competitive ELISA based on glass capillary for rapid and accurate detection of HBsAg. Methods In this study, the amino groups were modified to the surface of glass capillaries after a series treatment, following the HBsAg is coupled to the glass capillaries by carbodiimide method. The HRP labeled anti HBsAg antibody was prepared by the sodium periodate method, then the direct competitive ELISA was established by the modified glass capillaries for rapid and accurate detection of HBsAg. Results The linear range of this method was from 1 to 300 ng/mL (R2 = 0.996) and the limit of detection was 0.13 ng/mL. Conclusion This method has a high precision and precise, in addition it has high specificity in detecting HBsAg in serum. Therefore, the direct competitive ELISA based on glass capillaries could complete the rapid and accurate detection of HBsAg in serum, which shows a great potential in the clinic detection of HBsAg. [ABSTRACT FROM AUTHOR]

Chronic hepatitis B caused by hepatitis B virus (HBV) infection remains a major public health problem worldwide, and functional cure and even complete cure of chronic hepatitis B are the goals pursued by drug researchers. At present, widely used nucleos(t) ide analogues and interferon therapy fail to achieve a high cure rate. This article reviews the anti - HBV drugs/therapies under research, including viral entry inhibitors, capsid inhibitors, HBsAg inhibitors, immune modulators, gene editing, and cell therapies, and summarizes related clinical research findings, so as to clarify the latest advances in this field and the new ideas in drug research and development. [ABSTRACT FROM AUTHOR]

Objective To investigate the value of baseline HBsAg quantification in predicting HBsAg clearance in pegylated interferon α-2 b(PEG-INFα-2 b)-treated chronic hepatitis B(CHB) patients with a low level of HBsAg.Methods A retrospective analysis was performed for 51 HBeAg-negative CHB patients who achieved HBV DNA<20 IU/ml after nucleos(t) ide analogue(NA) treatment,had a normal level of alanine aminotransferase(ALT) and an HBsAg quantification of>0.05 IU/ml and<1500 IU/ml,and received sequential PEG-INFα-2 b treatment in Hepatobiliary Hospital of Jilin from March 2016 to September 2018.The clinical data of serum HBsAg quantification,anti-HBs quantification,HBV DNA quantification,and ALT level were collected at baseline and at weeks 12,24,36,and48 of treatment.At week 48 of treatment,19 patients with HBsAg clearance were enrolled as response group,and 32 patients without HBsAg clearance were enrolled as non-response group.The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups,and the receiver operating characteristic(ROC) curve was used to analyze the value of baseline HBsAg quantification in predicting HBsAg clearance at week 48 of treatment.Results At week 48 of treatment,19 patients(37.25%) achieved HBsAg clearance,among whom 7(7/19,36.84%) had a baseline HBs Ag quantitation of ≤10 IU/ml,9(9/19,47.37%) had a baseline HBs Ag quantitation of>10 IU/ml and ≤100 IU/ml,1 had a baseline HBs Ag quantitation of>100 IU/ml and ≤500 IU/ml,1 had a baseline HBs Ag quantitation of>500 IU/ml and ≤1000 IU/ml,and 1 had a baseline HBs Ag quantitation of>1000 IU/ml and ≤1500 IU/ml;8 patients(15.69%) achieved HBs Ag seroconversion,among whom 4 had an anti-HBs level of>10 IU/L and ≤100 IU/L,3 had an anti-HBs level of>100 IU/L and ≤500 IU/L,and 1 had 500 IU/L.The response group had a significantly lower baseline HBs Ag quantitation than the non-response group [16.38(2.25-61.62) IU/ml vs 363.73(110.14-927.72) IU/ml,Z=-4.442,P<0.001].At weeks12 and 24 of treatment,both groups had an increase in serum ALT level,and there was a significant difference between the response group and the non-response group [week 12:82.00(55.00-123.00) U/L vs 49.00(34.00-65.00) U/L,Z=-2.286,P=0.005;week24:78.00(46.00-88.00) U/L vs 48.08(29.79-71.75) U/L,Z=-2.617,P=0.009].At weeks 12 and 24 of treatment,the response group had a significantly greater reduction in HBs Ag than the non-response group [week 12:91.77%(49.62%-99.28%) vs44.03%(15.75%-68.90%),Z=-3.312,P=0.001;week 24:99.00%(98.00%-100.00%) vs 77.94%(37.02%-89.60%),Z=-5.100,P<0.001].The patients were followed up for 24 weeks after drug withdrawal,and the results showed that all 19 patients with HBs Ag clearance achieved sustained response and 7 patients achieved HBs Ag seroconversion.The ROC curve analysis showed that baseline HBs Ag quantification predicted HBs Ag clearance rate at week 48 of treatment,with an optimal predictive value of 86.36 IU/ml,an area under the ROC curve of0.875(95% confidence interval:0.764-0.986),a sensitivity of 84.4%,and a specificity of 84.2%.The positive predictive value and negative predictive value were 84.21% and 84.37%,respectively.Conclusion In CHB patients with a low level of HBs Ag(≤100 IU/ml) treated by NAs,sequential PEG-INFα-2 b treatment can significantly improve HBs Ag clearance and seroconversion and help with HBs Ag clearance at week48 of treatment especially in those with a significant reduction in HBs Ag and a significant increase in ALT in the early stage of treatment.Baseline HBs Ag quantification<86.36 IU/ml can predict HBs Ag clearance at week 48 of treatment. [ABSTRACT FROM AUTHOR]

BackgroundFollowing World Health Organization recommendations that a quality control (QC) system be implemented in African blood centers, a pilot study of the performance of human immunodeficiency virus antibody (anti-HIV), hepatitis B surface antigen (HBsAg), and hepatitis C virus antibody (anti-HCV) testing by several Sub-Saharan African blood centers was initiated.Study design and methodsA reference laboratory sent a panel of 25 samples to six African blood center laboratories. The panel included eight negative samples; four anti-HIV-1–, one anti-HIV-2–, four anti-HCV–, and five HBsAg-positive samples; and three samples consisting of mixtures of two sera to mimic coinfections. Sensitivity, specificity, and overall quality (correct positive or negative status) scores were calculated.ResultsFrom the 21 sets of results obtained (seven for each virus), eight were from rapid tests (two for HIV, three for HBV, and three for HCV) and 13 were from enzyme immunoassays (EIAs; all HIV EIAs were antigen/antibody combination assays). Overall assay sensitivity was 98% for HIV, 75% for HBV, and 88% for HCV; agreement between blood centers using the same assay was good. Sensitivity of rapid tests was notably poorer than EIAs, with overall sensitivity quality scores of 64.5% for rapid tests (20% for HBsAg rapid tests) compared to 100% for EIAs. The overall specificity quality scores were 98.3 and 94.5% for EIAs and rapid tests, respectively.ConclusionsThis pilot QC study organized for blood centers of Sub-Saharan Africa showed the feasibility of the approach despite some logistic constraints. Although interlaboratory variability was small, the poor performance of rapid tests, especially for HBsAg, raises policy questions about their use as the only screening assay.

BackgroundLittle current information is available for prevalence of vertically-transmitted infections among the Afghan population. The purpose of this study is to determine prevalence and correlates of human immunodeficiency virus (HIV), syphilis, and hepatitis B and C infection among obstetric patients and model hepatitis B vaccination approaches in Kabul, Afghanistan.MethodsThis cross-sectional study was conducted at three government maternity hospitals in Kabul, Afghanistan from June through September, 2006. Consecutively-enrolled participants completed an interviewer-administered survey and whole blood rapid testing with serum confirmation for antibodies to HIV, T. pallidum, and HCV, and HBsAg. Descriptive data and prevalence of infection were calculated, with logistic regression used to identify correlates of HBV infection. Modeling was performed to determine impact of current and birth dose vaccination strategies on HBV morbidity and mortality.ResultsAmong 4452 women, prevalence of HBsAg was 1.53% (95% CI: 1.18 - 1.94) and anti-HCV was 0.31% (95% CI: 0.17 - 0.53). No cases of HIV or syphilis were detected. In univariate analysis, HBsAg was associated with husband's level of education (OR = 1.13, 95% CI: 1.01 - 1.26). Modeling indicated that introduction of birth dose vaccination would not significantly reduce hepatitis-related morbidity or mortality for the measured HBsAg prevalence.ConclusionIntrapartum whole blood rapid testing for HIV, syphilis, HBV, and HCV was acceptable to patients in Afghanistan. Though HBsAg prevalence is relatively low, periodic assessments should be performed to determine birth dose vaccination recommendations for this setting.

This article summarizes the risk of hepatocellular carcinoma in patients with chronic hepatitis B virus infection after HBsAg seroclearance, as well as its mechanism and implications. [ABSTRACT FROM AUTHOR]

BackgroundThere is a clear need for methods to recruit and retain donors without compromising blood safety. Although prior studies report lower viral prevalence rates in repeat donors than those in first-time donors, it is unknown if this relationship holds after a lapse of several years between donations.Study design and methodsA total of 6.4 million allogeneic donations collected at five US blood centers from 1991 through 1998 were classified by donation history (first-time vs. repeat) and by length of time between donations (lapsed interval length). The prevalence of HCV, HIV, and HBsAg was compared by donation history and lapsed interval length. The relationship between lapsed interval length and donor demographics was explored.ResultsRepeat donors who delayed their return for over 5 years were significantly less likely to test positive for a viral infection than were first-time donors. The likelihood of a positive test result appeared to increase steadily with lapsed interval length for HCV and HBsAg, but not for HIV. Younger, less educated, and nonwhite donors were less likely to return than others.ConclusionsRecruitment of donors who have not returned for several years could be an effective way to increase the blood supply while preserving blood safety. Understanding the relationship of donor demographics to return behavior is important for recruitment efforts.

Background/AimsWe aimed to clarify the association of hepatitis B surface antigen (HBsAg)/hepatitis B core antigen (HBcAg) with the disease status and treatment response in patients with chronic hepatitis B (CHB).Methods : We investigated 171 biopsy-proven entecavir-treated CHB patients (109 hepatitis B e antigen [HBeAg]-positive, 62 HBeAg-negative). HBcAg expression was positive when ≥10% of hepatocytes stained, and classified into nuclear, mixed, and cytoplasmic patterns. HBsAg expressions were intracytoplasmic (diffuse, globular, and submembranous) and membranous. The histologic activity index (HAI) and fibrosis stage followed Ishak system.Results : In HBeAg-positive patients, older age, increased HAI score, advanced fibrosis, and reduced viral load were observed when HBcAg expression shifted from nucleus to cytoplasm in HBcAg-positive patients, and HBsAg expression from non-submembranous to submembranous in HBcAg-negative patients (all, p

People living with HIV (PWH) have been shown to bear a higher burden of hepatitis B virus (HBV) due to shared routes and risk factors for transmission. Populations such as men who have sex with men (MSM) are at an increased risk of both being infected with HBV and HIV, that places them at higher risk of hepatocellular carcinoma. Using weighted and adjusted multilevel logistic regression, we characterized the prevalence and correlates of hepatitis B surface antigen (HBsAg) among MSM living with HIV across 12 Indian cities from 2012 to 2013. Overall, the prevalence of HBsAg was 8% (range across cities: 0.5%-19%). Being between the ages of 25-34, and 35-44 increased the odds of having chronic HBV infection compared to MSM 24 years or younger. Daily or seasonal employment and being unemployed increased the odds of HBsAg prevalence compared to those with monthly or weekly wages. Sexual risk behaviours such as having had sex with both men and women in the prior 6 months and history of sex work increased the odds of having HBV. Ever having insertive sex with a man or hijra (assigned male at birth, currently identifies as female/nonbinary) was negatively associated with HBV. Despite the existence of efficacious vaccines, HBV continues to have high prevalence among PWHs. Programmes to increase early screening, vaccinations and HBV literacy are urgently needed. Integrating HBV and HIV programmes for MSM populations could be critical in addressing this dual burden and improving outcomes for both infections., (© 2024 John Wiley & Sons Ltd.)

CLL is associated with an increased risk of infectious complications. Treatment with BTK or BCL-2 inhibitors does not seem to increase significantly the risk of opportunistic infections, but the role of combination therapies including BTK and/or BCL-2 inhibitors remains to be established. Various infectious complications can be successfully prevented with appropriate risk management strategies. In this paper we reviewed the international guidelines on prevention and management of infectious complications in patients with CLL treated with BTK or BCL-2 inhibitors. Universal pharmacological anti-herpes, antibacterial or antifungal prophylaxis is not warranted. Reactivation of HBV should be prevented in HBsAg-positive subjects. For HBsAg-negative/HBcAb-positive patients recommendations differ, but in case of combination treatment should follow those for other, particularly anti-CD20, agent. Immunization should be provided preferably before the onset of treatment. Immunoglobulin therapy has favourable impact on morbidity but not mortality in patients with hypogammaglobulinemia and severe or recurrent infections. Lack of high-quality data and heterogeneity of patients or protocols included in the studies might explain differences among the main guidelines. Better data collection is warranted., Competing Interests: Declaration of competing interest F.R.M.: Funding for research and educational projects from Abbvie, Takeda, Janssen. Member of Advisory Board for AbbVie, Beigene, AstraZeneca, Janssen. A.M.F.: Member of Advisory Board for Janssen, Beigene, AstraZeneca, Abbvie. A.V.: Member of Advisory Board for AbbVie, Beigene, AstraZeneca, Janssen, CSL Behring, Takeda. C.V.: Consultancy fees from Abbvie and Astra Zeneca. M.B.: speaker/advisor fees from MSD, BioMérieux, Gilead, AstraZeneca, Advanz, and Pfizer, all outside the submitted work. C.O.: None. E.Z.: None. M.M.: grant from Gilead paid to the Institution; speaker/advisor fees from Allovir, BioMérieux, Gilead, Janssen, Moderna, Mundipharma and Pfizer, all outside the submitted work., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The antiviral activity of interferon gamma (IFNγ) against hepatitis B virus (HBV) was demonstrated both in vivo and in vitro in a previous study. IFNγ can suppress HBV replication by accelerating the decay of replication-competent nucleocapsids of HBV. However, in this study, we found that the direct application of the mouse IFNγ (mIFNγ) expression plasmid to the liver of an HBV hydrodynamic injection (HI) mouse model led to the persistence of HBV, as indicated by sustained HBsAg and HBeAg levels in the serum as well as an increased percentage of the HBsAg positive mice, whereas the level of HBV DNA in the serum and the expression of HBcAg in the liver were inhibited at the early stage after HI. Meanwhile, we found that the productions of both HBcAb and HBsAb were suppressed after the application of mIFNγ. In addition, we found that HBV could be effectively inhibited in mice immunized with HBsAg expression plasmid before the application of mIFNγ. Furthermore, mIFNγ showed antiviral effect and promoted the production of HBsAb when the mice subjected to the core-null HBV plasmid. These results indicate that the application of mIFNγ in the HBV HI mouse model, the mice showed defective HBcAg-specific immunity that impeded the production of HBcAb and HBsAb, finally allowing the persistence of the virus. Moreover, IFNγ-induced negative immune regulatory factors also play an important role in virus persistence., Competing Interests: Declaration of competing interest The authors of this study declare that they do not have any financial or commercial conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background & Aims: Mechanisms behind the impaired response of antigen-specific B cells to therapeutic vaccination in chronic hepatitis B virus (HBV) infection remain unclear. The development of vaccines or strategies to overcome this obstacle is vital for advancing the management of chronic hepatitis B., Methods: A mouse model, denominated as E6F6-B, was engineered to feature a knock-in of a B-cell receptor (BCR) that specifically recognizes HBsAg. This model served as a valuable tool for investigating the temporal and spatial dynamics of humoral responses following therapeutic vaccination under continuous antigen exposure. Using a suite of immunological techniques, we elucidated the differentiation trajectory of HBsAg-specific B cells post-therapeutic vaccination in HBV carrier mice., Results: Utilizing the E6F6-B transfer model, we observed a marked decline in antibody-secreting cells 2 weeks after vaccination. A dysfunctional and atypical pre-plasma cell population (BLIMP-1 + IRF4 + CD40 - CD138 - BCMA - ) emerged, manifested by sustained BCR signaling. By deploying an antibody to purge persistent HBsAg, we effectively prompted the therapeutic vaccine to provoke conventional plasma cell differentiation. This resulted in an enhanced anti-HBs antibody response and facilitated HBsAg clearance., Conclusions: Sustained high levels of HBsAg limit the ability of therapeutic hepatitis B vaccines to induce the canonical plasma cell differentiation necessary for anti-HBs antibody production. Employing a strategy combining antibodies with vaccines can surmount this altered humoral response associated with atypical pre-plasma cells, leading to improved therapeutic efficacy in HBV carrier mice., Impact and Implications: Therapeutic vaccines aimed at combatting HBV encounter suboptimal humoral responses in clinical settings, and the mechanisms impeding their effectiveness have remained obscure. Our research, utilizing the innovative E6F6-B mouse transfer model, reveals that the persistence of HBsAg can lead to the emergence of an atypical pre-plasma cell population, which proves to be relevant to the potency of therapeutic HBV vaccines. Targeting the aberrant differentiation process of these atypical pre-plasma cells stands out as a critical strategy to amplify the humoral response elicited by HBV therapeutic vaccines in carrier mouse models. This discovery suggests a compelling avenue for further study in the context of human chronic hepatitis B. Encouragingly, our findings indicate that synergistic therapy combining HBV-specific antibodies with vaccines offers a promising approach that could significantly advance the pursuit of a functional cure for HBV., (Copyright © 2024 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: New treatment modalities for hepatocellular carcinoma (HCC) are desperately critically needed, given the lack of specificity, severe side effects, and drug resistance with single chemotherapy. Engineered bacteria can target and accumulate in tumor tissues, induce an immune response, and act as drug delivery vehicles. However, conventional bacterial therapy has limitations, such as drug loading capacity and difficult cargo release, resulting in inadequate therapeutic outcomes. Synthetic biotechnology can enhance the precision and efficacy of bacteria-based delivery systems. This enables the selective release of therapeutic payloads in vivo., Methods: In this study, we constructed a non-pathogenic Escherichia coli ( E. coli ) with a synchronized lysis circuit as both a drug/gene delivery vehicle and an in-situ (hepatitis B surface antigen) Ag (ASEc) producer. Polyethylene glycol (CHO-PEG 2000 -CHO)-poly(ethyleneimine) (PEI 25k )-citraconic anhydride (CA)-doxorubicin (DOX) nanoparticles loaded with plasmid encoded human sulfatase 1 (hsulf-1) enzyme (PNPs) were anchored on the surface of ASEc (ASEc@PNPs). The composites were synthesized and characterized. The in vitro and in vivo anti-tumor effect of ASEc@PNPs was tested in HepG2 cell lines and a mouse subcutaneous tumor model., Results: The results demonstrated that upon intravenous injection into tumor-bearing mice, ASEc can actively target and colonise tumor sites. The lytic genes to achieve blast and concentrated release of Ag significantly increased cytokine secretion and the intratumoral infiltration of CD4/CD8 + T cells, initiated a specific immune response. Simultaneously, the PNPs system releases hsulf-1 and DOX into the tumor cell resulting in rapid tumor regression and metastasis prevention., Conclusion: The novel drug delivery system significantly suppressed HCC in vivo with reduced side effects, indicating a potential strategy for clinical HCC therapy., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Yang et al.)

Introduction: Infection by hepatitis B virus (HBV) is a major issue in public health. The prevalence of HBV in Chad is 12.4%, all age groups considered. Here, we aimed to determine the prevalence of HBV and its associated factors among university students in N'Djamena, the country's capital., Methods: A cross-sectional survey of students at either the University of N'djamena or Emi Koussi University was conducted from 3 to 23 July 2021. All participating students provided signed, informed consent and were included in the study consecutively. Blood samples were collected, and serum tested for hepatitis B surface antigen (HBsAg) using the Determine HBsAg rapid test kit, with confirmation of positive tests on an Abbott Architect i1000SR analyzer. Descriptive analysis and logistic regression were used to determine associations between the outcome variable and independent/covariate variables., Results: A total of 457 students with a median age of 24 years were included across different faculties. The prevalence of HBV infection was 14.87% (68/457). Most students (75%) were aged 25 years or less. Unprotected sex was reported by 64.9% of the students and multiple sexual partners by 53.6%. Furthermore, 45.7% of them reported having no knowledge of hepatitis B. Having an HBsAg-positive mother (AOR: 2.11), having a history of transcutaneous medical procedures (AOR: 2.97) and living with a family (AOR: 4.63) were significantly associated with HBV status. Age ≥26 years appeared as a protective factor (AOR = 0.41)., Conclusion: Our study detected a high, 14.87% prevalence of HBV infection among students in N'djamena, Chad, and shed light on its associated factors. HBV prevention strategies should include raising awareness among students, making full hepatitis vaccination mandatory before children begin school, promoting mass screening to identify and treat chronic HBV carriers and reduce transmission, and reducing the cost of vaccination., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Debsikréo 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.)

Background: The low prevalence of HDV infection in the United States could be attributed to insufficient testing rate, which can result in an underestimation of the true burden of HDV. The primary objective of this study is to quantify the prevalence of and factors associated with HDV antibody (anti-HDV) or RNA testing, among participants with positive HBsAg in the Veterans Health Administration (VHA)., Methods: We conducted a retrospective cohort study of participants who tested positive for HBsAg between January 2000 and December 2022 within the VHA. We identified those who were tested for HDV, and patient and provider-level factors associated with HDV testing., Results: Of 41,658 participants with positive HBsAg who had follow-up, 4438 (10.7%) were tested at least once for HDV, of which 135 (3.0%) were positive. Participants in the Northeast (adjusted odds ratio [aOR]: 1.30, 95% CI: 1.17-1.44, p<0.001), and receiving hepatology care (aOR: 1.38, 95% CI: 1.24-1.54, p<0.001) were more likely, while those in the Midwest (aOR: 0.69, 95% CI: 0.60-0.79, p<0.001), under the care of a primary care provider (aOR: 0.61, 95% CI: 0.50-0.74, p<0.001), Blacks (aOR: 0.85, 95% CI: 0.77-0.94, p=0.001), participants who were HCV antibody-positive (aOR: 0.89, 95% CI: 0.81-0.99, p=0.03), and participants who were HIV-positive (aOR: 0.80, 95% CI: 0.71-0.90, p<0.001) were less likely to be tested for HDV., Conclusions: HDV screening rates in the VHA remain low overall. Participants who are Black, living in the Midwest, patients who are HIV-positive, and patients who are HCV-positive are less likely to be tested for HDV. These results suggest that risk-based screening strategies are ineffective in the VHA and highlight the need for refining testing strategies to increase HDV screening rates., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Hepatitis B Virus (HBV) is a major driver of infectious disease mortality. Curative therapies are needed and ideally should induce CD8 T cell-mediated clearance of infected hepatocytes plus anti-hepatitis B surface antigen (HBsAg) antibodies (anti-HBs) to neutralize residual virus. We developed a novel therapeutic vaccine using non-replicating arenavirus vectors. Antigens were screened for genotype conservation and magnitude and genotype reactivity of T cell response, then cloned into Pichinde virus (PICV) vectors (recombinant PICV, GS-2829) and lymphocytic choriomeningitis virus (LCMV) vectors (replication-incompetent, GS-6779). Alternating immunizations with GS-2829 and GS-6779 induced high-magnitude HBV T cell responses, and high anti-HBs titers. Dose schedule optimization in macaques achieved strong polyfunctional CD8 T cell responses against core, HBsAg, and polymerase and high titer anti-HBs. In AAV-HBV mice, GS-2829 and GS-6779 were efficacious in animals with low pre-treatment serum HBsAg. Based on these results, GS-2829 and GS-6779 could become a central component of cure regimens., Competing Interests: Potential conflicts of interest . M. M., S. D., T. G., R. C., C. L., A. T., J. P., S. P. F., and S. B. are or were employees of Gilead Sciences. S. S., S. A. E., D. D., H. L., and K. O. are employees of Hookipa Pharma. M. D. R. has financial relationships with CaroGen Corporation, received royalties from a Yale University patent, and received research funding from Gilead Sciences. Al; other authors reported no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Chronic hepatitis B, a major cause of liver disease and cancer, affects >250 million people worldwide. Currently there is no cure, only suppressive therapies. Efforts to develop finite curative hepatitis B virus (HBV) therapies are underway, consisting of combinations of multiple novel agents with or without nucleos(t)ide reverse-transcriptase inhibitors. The HBV Forum convened a webinar in July 2021, along with subsequent working group discussions to address how and when to stop finite therapy for demonstration of sustained off-treatment efficacy and safety responses. Participants included leading experts in academia, clinical practice, pharmaceutical companies, patient representatives, and regulatory agencies. This Viewpoints article outlines areas of consensus within our multistakeholder group for stopping finite therapies in chronic hepatitis B investigational studies, including trial design, patient selection, outcomes, biomarkers, predefined stopping criteria, predefined retreatment criteria, duration of investigational therapies, and follow-up after stopping therapy. Future research of unmet needs are discussed., Competing Interests: Conflicts of interest. M. G. P. received honoraria from Wainright Corporation, received consulting fees (to the author) from Aligos Therapeutics and Antios Therapeutics, and participates on a data safety monitoring board for Excision Biotherapeutics. M. F. Y. reports grants and research support from AbbVie, Assembly Biosciences, Arrowhead Pharmaceuticals, Bristol Myers Squibb (BMS), Fujirebio, Gilead Sciences, Immunocore, Merck Sharp and Dohme (MSD), Springbank Pharmaceuticals, Sysmex Corporation, and Roche and reports honoraria for advisory boards/lectures from AbbVie, Aligos Therapeutics, AiCuris, Antios Therapeutics, Arbutus Biopharma, Arrowhead Pharmaceuticals, Assembly Biosciences, BMS, Clear B Therapeutics, Dicerna Pharmaceuticals, Finch Therapeutics, Fujirebio, GlaxoSmithKline (GSK), Gilead Sciences, Immunocore, Janssen, MSD, Roche, Springbank Pharmaceuticals, Silverback Therapeutics, Sysmex, and Vir Biotechnology. N. T. reports institutional grant support from the National Institutes of Health, GSK, Genentech-Roche, Helio Health, Durect, Gilead Sciences, Eiger Pharmaceuticals, and Madrigal; provision of educational materials from Clinical Care Options and Simply Speaking; honoraria for invited lectures in conferences from the Canadian Association for the Study of the Liver (CASL), the European Association for the Study of the Liver (EASL), Pakistan Society for the Study of Liver Diseases (PSSLD), the Asian Pacific Association for the Study of the Liver, GUILD, and the International Liver Transplantation Society (ILTS) and for invited lectures from University of Alabama, Duke University, Houston Methodist, University of California, Iowa University; support for travel for invited lectures from the American Association for the Study of Liver Diseases (AASLD), EASL, GUILD, CASL, PSSLD, International Association for the Study of the Liver (IASL), and ILTS; and roles as president of the governing board for the AASLD and a steering committee member for the Hepatitis B Foundation and HBV Forum. J. F. is a former employee of and owns stock in Aligos Therapeutics. P. L. reports honoraria for lectures or presentations from BMS, Roche, Gilead Sciences, GSK, AbbVie, MSD, Arrowhead, Alnylam, Janssen, Vir Biotechnology, Springbank, MYR, Eiger, Antios, and Aligos. E. G. is an advisory board member/consultant for AbbVie, Gilead Sciences, Intellia Pharmaceuticals, Janssen, and Roche. C. H. is an employee of and owns stock in Vir Biotechnology. L. M. S. is a former employee of and owns stock in Assembly Biosciences. M. K. M. reports being an advisor to Gilead, GSK, and Roche (advisory board payments to University College London Consultants); is a minor coapplicant on patent application 1200281465; and reports the following pending patents: international patent application PCT/GB2020/053034 (ACAT inhibitors for liver disease) and UK patent application 2109807.4 (CD14/CD8 T cells). P. Mendez is a former employee of Gilead Sciences and owns stock or stock options in Gilead Sciences Inc. I. L. D. owns stock in Johnson & Johnson. T. B. reports institutional grant support from AbbVie, BMS, Gilead, MSD/Merck, Humedics, Intercept, Merz, Norgine, Novartis, Orphalan, and Sequana Medical; consulting fees and honararia from AbbVie, Alexion, Bayer, Falk Foundation, Gilead, GSK, Eisai, ENYO Pharma, HepaRegeniX, Humedics, Intercept, Ipsen, Janssen, MedUpdate, MSD/Merck, Novartis, Orphalan, Roche, Sequena Medical, SIRTEX, SOBI, and Shionogi; and support for attending meetings and/or travel from Gilead, AbbVie, Intercept, and Janssen. S. W. reports institutional support from Gilead and is an unpaid board member for the Hepatitis B Foundation. S. B. reports travel support, direct booking, and payment for travel by the HBV Forum for HBV Forum 10 in Vienna, Austria, and by AASLD for the EASL/AASLD HBV Endpoints 2022 meeting in Washington, DC. V. M. reports grant funding for the HBV Forum from Abbott, Aligos Therapeutics, AlloVir, Altimmune, Antios Therapeutics, Arrowhead Pharmaceuticals, Assembly Biosciences, DDL Diagnostic Laboratory, Eiger, Enyo Pharma, Gilead Sciences, GSK, the Hepatitis B Foundation, Immunocore, Janssen, LabCorp, Monogram Biosciences, Quest Diagnostics, the RFS Family Foundation, Roche, VenatorX, Vir Biotechnology, Virion Therapeutics, and Viroclinics. O. L. is an employee of Janssen and owns stock in Johnson & Johnson. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background and Aims: To investigate the impact of intrahepatic cholestasis of pregnancy (ICP) with hepatitis B virus (HBV) infection on pregnancy outcomes., Methods: We selected 512 pregnant women, collected the data including maternal demographics, main adverse pregnancy outcomes and maternal HBV infected markers HBeAg and HBV-DNA loads status, then have a comparative analysis., Results: There were 319 solitary ICP patients without HBV infection (Group I) and 193 ICP patients with HBV infection. Of the latter, there were 118 cases with abnormal liver function(Group II) and 80 cases with normal liver function(Group III). All HBV-infected pregnant women with ICP were divided into hepatitis Be antigen (HBeAg)-positive group (102 cases) and HBeAg-negative group (91 cases), according to the level of the serum HBeAg status; and into high viral load group (92 cases), moderate viral load group (46 cases) and low viral load group (55 cases) according to the maternal HBV-DNA level. Group II had a higher level of serum total bile acids, transaminase, bilirubin as well as a higher percentage of premature delivery, neonatal intensive care unit (NICU) admission and meconium-stained amniotic fluid (MSAF) compared with the other two groups(P < 0.05), but there were no significant differences in the above indicators between the Group I and Group III. Among the HBV-infected patients with ICP, HBeAg-positive group had a higher level of serum transaminase, bilirubin and bile acid as well as earlier gestational weeks of delivery, lower birth weight of new-borns and a higher rate of NICU admission than HBeAg-negative group (P < 0.05). Those with a high viral load (HBV-DNA > 10 6  IU/ml) had a higher level of transaminase, bilirubin, and bile acid as well as shorter gestational weeks of delivery, lower birth weight of new-borns and a higher rate of NICU admission compared with those with a low or moderate viral load (P < 0.05)., Conclusion: HBV-infected pregnant women with ICP combined with abnormal liver function have more severe liver damage, a higher percentage of preterm birth and NICU admission. HBeAg-positive status and a high HBV-DNA load will increase the severity of conditions in HBV-infected pregnant women with ICP. HBV-infected patients with ICP who have abnormal liver function, HBeAg-positive or a high viral load should be treated more actively., (© 2024. The Author(s).)

The value of detecting hepatitis B virus (HBV), pregenomic RNA (pgRNA), and hepatitis B core-related antigen (HBcrAg), both separately and jointly, in the management of HBV patients undergoing treatment with Nucleotide Analog was investigated. A total of 149 HBV patients who were being treated with Nucleotide Analog were enrolled in this study. The quantitative levels of HBV pgRNA and HBcrAg in the sera of these patients were determined, aiming to comprehend their replication levels and expression during the course of antiviral therapy. The patients were separated into 3 groups based on treatment duration: treatment time ≤ 12 months, treatment time ranging from 12 months to <60 months, and treatment time ≥ 60 months. Significantly different levels of HBcrAg and HBV pgRNA were observed among 3 groups (P < .05). In the group of patients with positive hepatitis B e antigen, both HBcrAg and pgRNA levels were higher compared to the group with negative hepatitis B e antigen, and this difference between the 2 groups was found to be statistically significant. Stratified analysis based on levels of hepatitis B surface antigen (HBsAg) revealed that the group with HBsAg levels < 100 IU/mL had lower levels of both HBcrAg and pgRNA compared to the group with HBsAg levels ≥ 100 IU/mL (P < .001). Following antiviral therapy, various degrees of transcription of covalently closed circular DNA continue to exist within the liver of HBV patients. The levels of serum HBcrAg and HBV pgRNA vary among patients with different treatment durations, indicating their efficacy in evaluating disease conditions during antiviral therapy., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: No study has comparing hepatitis B virus (HBV) relapse rates among patients with both cancer and hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) who completed anti-viral prophylaxis for chemotherapy and then stopped taking entecavir or tenofovir alafenamide (TAF)., Methods: A total of 227 HBeAg-negative cancer patients without cirrhosis who previously took entecavir (n = 144) or TAF (n = 83) for antiviral prophylaxis were enrolled., Results: The cumulative incidence of virological and clinical relapse at 2 years was 37% and 10.4%, respectively, in the entecavir group, and 46.7% and 19.5%, respectively, in the TAF group. The multivariate analysis revealed that the use of hematologic malignancy, TAF use, and high-viremia group at baseline were independent risk factors for virological relapse, and use of rituximab, TAF use, higher FIB-4 index and high-viremia group at baseline were independent risk factors for clinical relapse. After propensity score-matching, the patients who discontinued TAF therapy still exhibited higher virological (P = 0.031) and clinical relapse rates (P = 0.012) than did those who discontinued entecavir therapy. The patients were allocated to high- (> 2000 IU/mL), moderate- (between 20 and 2000 IU/mL) and low- (< 20 IU/mL) viremia groups. In the high-viremia group, those who had taken TAF for antiviral prophylaxis had higher rates of virological and clinical relapse than did those who had taken entecavir; in the moderate- and low-viremia groups, no significant difference in virological and clinical relapse rates was detected between the entecavir and TAF groups. Three patients experienced hepatic decompensation upon clinical relapse. All three patients were lymphoma and underwent rituximab therapy. One patient developed acute on chronic liver failure and died even though timely retreatment., Conclusions: In patients with both cancer and CHB who underwent antiviral prophylaxis, TAF use was associated with a higher chance of HBV relapse than entecavir use after nucleos(t)ide analogue cessation, particularly in the high-viremia group. Patients who are hematologic malignancy and undergo a rituximab-containing cytotoxic therapy should be monitored closely after withdrawal from prophylactic NA treatment., (© 2024. The Author(s).)

Introduction: Home-based self-collected dried blood spot (DBS) sampling could simplify sexual health and preexposure prophylaxis care and reduce sexually transmitted infections (STIs) clinic visits for men who have sex with men (MSM). We compared the performance of DBS to venipuncture collected blood samples to test four STIs and creatinine concentration., Methods: We invited MSM clients of the Amsterdam STI clinic to participate. Routinely collected peripheral blood was tested for syphilis treponemal antibody, HIV (HIV Ag/Ab), HCV (antibodies), HBV (HBsAg) and creatinine concentration. Participants received a home kit for DBS sampling, a return envelope and a questionnaire to evaluate the acceptability, feasibility and usability of DBS, measured on 5-point Likert scales, 1 representing complete disagreement and 5 complete agreement. We assessed sensitivity and specificity of DBS versus peripheral blood-based testing., Results: In 2020 to 2021, we included 410 participants; 211 (51.5%) returned a completed DBS card, 117 (28.5%) returned a partially filled card and 82 (20.0%) did not return a card. The sensitivity for syphilis was 90.8% and the specificity 84.3%. For both HIV Ag/Ab and HBsAg, the sensitivity and specificity were 100.0%. The sensitivity for HCV antibody was 80.0%, and the specificity was 99.2%. The DBS creatinine concentration was a mean of 5.3 μmol/L higher than in venipuncture obtained plasma. Participants' median willingness to take a future DBS was 4 (interquartile range, 3-5)., Discussion: Dried blood spot may be an acceptable method among MSM for STI testing and creatinine follow-up during preexposure prophylaxis use. However, collecting enough blood on DBS cards was a challenge, and sensitivities for syphilis and HCV serology were too low., Competing Interests: Conflict of Interest and Sources of Funding: None declared., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Sexually Transmitted Diseases Association.)