SEARCH · PubMed Health

Results for “HBV”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

PubMed2026

Genomic and transcriptomic features of HBV integration in treatment-naïve, HBeAg-positive children with chronic HBV infection.

BACKGROUND: Hepatitis B virus (HBV) integration represents a major obstacle to curing HBV; however, the landscape of HBV integration and local immune response to transcriptionally active viral integration in children with chronic HBV infection remain unclear. Herein, we aimed to elucidate this landscape in this population. METHODS: Genomic analyses using a probe-based capture strategy were performed on 18 children and 28 adults with chronic HBV infection. Spatial transcriptomics (ST) was performed on 12 children from our cohort and 3 adults from a public database. FINDINGS: All patients were hepatitis B e antigen (HBeAg)-positive and treatment-naïve. Genomically, children exhibited significantly lower clonal expansion level of HBV-integrated hepatocytes than adults, despite comparable unique breakpoint counts. After adjusting for confounding variables, age was identified as an independent risk factor for total frequency of unique integration breakpoints (b = 3.22, P = 0.005). Spatially, ST revealed that spots with transcriptionally active viral integration exhibited a sparse distribution and accounted for a low proportion of all spots in children. Notably, at these spots, children showed reduced adaptive immune cells (e.g., CD8+ T cells) but increased innate components (myeloid cells, Kupffer cells, activated dendritic cells) and APC co-stimulation, whereas adults exhibited a uniform reduction of immune cell populations. INTERPRETATION: Compared with adults, children exhibit lower clonal expansion of HBV-integrated hepatocytes and distinct immune profiles in response to transcriptionally active viral integration, offering new insights into their differing clinical course. FUNDING: Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education).

Humans↗

PubMed2025

Identification of glycogen synthase kinase 3alpha/beta as a host factor required for HBV transcription using high-throughput screening.

BACKGROUND AND AIMS: HBV leads to severe liver diseases, such as cirrhosis and HCC. Identification of host factors that regulate HBV replication can provide new therapeutic targets. The discovery of sodium taurocholate cotransporting polypeptide (NTCP) as an HBV entry receptor has enabled the establishment of hepatic cell lines for analyzing HBV infection and propagation. Using this new system, studies aimed at identifying host factors that regulate HBV propagation have increased. APPROACH AND RESULTS: We established an HBV-based-reporter gene expression system that mimics HBV replication from transcription to virus egress. Using this approach, we screened 1827 Food and Drug Administration-approved compounds and identified glycogen synthase kinase 3 (GSK3)alpha/beta inhibitors, including AZD1080, CHIR-98014, CHIR-98021, BIO, and AZD2858, as anti-HBV compounds. These compounds suppressed HBeAg and HBsAg production in HBV-infected human primary hepatocytes. Proteome analysis revealed that GSK3alpha/beta phosphorylated forkhead box K1/2 (FOXK1/2)s. A double-knockout of FOXK1/2 in HBV-infected HepG2-NTCP cells reduced HBeAg and HBsAg production. The rescue of FOXK2 expression, but not FOXK1 expression, in FOXK1/2-double-knockout cells restored HBeAg and HBsAg production. Importantly, phosphorylation of FOXK2 at Ser 424 is required for GSK3alpha/beta-mediated HBeAg and HBsAg production. We observed the binding of FOXK2 to HBV DNA in HepG2-NTCP cells. CONCLUSIONS: Our recombinant HBV-based screening system enables the discovery of new targets. Using our approach, we identified GSK3 inhibitors as potential anti-HBV agents.

Humans↗

PubMed2026

Sex Hormone Receptors, HBV Integrations and Their Prognostic Predictive Value Among Hepatocellular Carcinoma Patients.

Hepatocellular carcinoma (HCC) related to hepatitis B virus (HBV) infection predominantly affects males, yet few studies have investigated the association between sex hormones and HBV integrations, and their involvement in HCC prognosis. We assessed estrogen receptor alpha (ERα) and androgen receptor (AR) expression via immunohistochemistry on tissue microarrays constructed from 426 HBV-related HCC samples. HBV integration features were determined using HBV-captured sequencing data. Logistic regression models were utilized to evaluate the association between sex hormone receptor expression level and HBV integration features. Cox regression models, combined with machine learning (ML) methods, were implemented to investigate the prognostic value of sex hormone receptors and HBV integrations concerning overall survival. We found high AR expression level was significantly associated with higher HBV integration levels (adjusted odds ratio [aOR] = 1.84, 95% confidence interval [CI]: 1.09-3.11, P for trend = 0.012), TERT integration (aOR = 2.34, 95% CI: 1.16-4.74, P for trend = 0.047), intergenic integration (aOR = 2.25, 95% CI: 1.20-4.24, P for trend = 0.021), and promoter integration (aOR = 1.81, 95% CI: 1.00-3.31, P for trend = 0.034). The inclusion of sex hormone receptors and HBV integrations in the predictive models led to improvements across all performance metrics in the Cox regression analyses (AUC improvement: 0.014 [Training], 0.026 [Validation]) and the ML (AUC improvement: 0.022 [Training]), although a slight deterioration in performance was noted in the ML validation set. The results suggested a relationship between AR expression level and HBV integration events, as well as the potential utility of HBV integration biomarkers and sex hormone receptor profiles in assessing post-surgical prognosis among HCC patients.

Humans↗

PubMed2026

A randomized trial of viral vector and adjuvanted protein HBV therapeutic vaccine in people with chronic hepatitis B on nucleos(t)ide analogs.

BACKGROUND: This study assessed the safety, efficacy, and immunogenicity of a therapeutic immunization strategy aimed at reaching a functional cure for chronic hepatitis B (CHB), relying on a heterologous prime-boost with viral vectors ChAd155-hIi-HBV and MVA-HBV, combined with sequential or concomitant administration of adjuvanted recombinant HBV proteins (HBc-HBs/AS01B). METHODS: This single-blind, randomized, controlled, first-in-human, phase 1/2 trial enrolled adults aged 18-65 years with HBeAg-negative CHB, virally suppressed on nucleos(t)ide analogs (NAs), with HBsAg >50 IU/mL. Participants received NAs and the following regimens of 4 doses (8-week intervals): sequential administration of ChAd155-hIi-HBV, MVA-HBV, and 2 HBc-HBs/AS01B doses; co-administration of ChAd155-hIi-HBV+HBc-HBs/AS01B, followed by 3 co-administered MVA-HBV+HBc-HBs/AS01B doses; 4 HBc-HBs/AS01B doses; 2 placebo doses followed by ChAd155-hIi-HBV and MVA-HBV administered alone or with HBc-HBs/AS01B; or 4 placebo doses. Safety, efficacy (≥1-log decrease in quantitative (q)HBsAg or HBsAg loss 24 weeks post-dose 4 [day (D)337]), antibody, and T-cell responses were evaluated. RESULTS: In all, 134 participants were vaccinated. Grade 3 solicited adverse events (AEs) (median duration: 2-3 days) were more frequent after co-administration (systemic: 59.3%; administration-site: 33.3%) than sequential administration (systemic: 10.3%; administration-site: 12.8%) of high-dose viral vectors and proteins. No vaccine-related or fatal serious AEs were reported. After 4 doses, no participant had HBsAg loss or ≥1-log decrease in qHBsAg (D337 vs. D1). Co-administration induced the strongest anti-HBs response (73.7% achieved anti-HBs ≥10 mIU/mL 2 weeks post-dose 4 vs. 40.0% after sequential administration). Both sequential and co-administration induced HBc-specific CD4+ and CD8+ T-cell responses, with a prime-boost effect of the viral vectors. CONCLUSIONS: Heterologous prime-boost with ChAd155-hIi-HBV and MVA-HBV, combined with sequential or co-administration of HBc-HBs/AS01B, had an acceptable safety profile, were moderately immunogenic, but no participants showed the expected efficacy outcome.

Humans↗

PubMed2025

CRISPR-mediated proximity labeling unveils ABHD14B as a host factor to regulate HBV cccDNA transcriptional activity.

BACKGROUND: The long-term goal of chronic hepatitis B research is a functional cure (HBsAg seroclearance). Although currently used nucleos(t)ide analogs can efficiently inhibit viral replication, they do not reduce viral RNAs or proteins produced from covalently closed circular DNA (cccDNA), and rarely achieve a functional cure. To overcome this situation, revealing the mode of the existence of cccDNA is required, including identifying the interreacting proteins with cccDNA. Here, we aimed to identify novel proteins that interact with cccDNA. METHODS: Using an in vitro HBV infection model and a sequence-specific proximity labelling method consisting of dead Cas9 and biotin identification (BioID2), we comprehensively determined proteins that possibly interact with cccDNA. After identifying the candidate proteins, the HBV RNA transcription levels were examined by knocking out the associated genes. RESULTS: We identified ABHD14B as a protein that interacts with cccDNA and inhibits HBV RNA transcription from cccDNA. ABHD14B decreases the acetylation levels of histone proteins that control the transcription levels of HBV RNA in cccDNA. Moreover, ABHD14B interacts with TFII-I, which binds directly to cccDNA in a sequence-dependent manner. These results suggest that the host protein, ABHD14B, is recruited to cccDNA via the TFII-I protein, inhibiting HBV RNA transcription from cccDNA by deacetylating cccDNA histones. CONCLUSIONS: ABHD14B was newly identified as a suppressor of HBV RNA transcription from cccDNA, which may improve our understanding of the mode of existence of cccDNA, providing a basis for development of a functional cure.

Humans↗

PubMed2026

Dual HBV cccDNA-linked HiBiT reporter hepatocyte models for screening of candidate cccDNA modulators.

Chronic hepatitis B remains difficult to cure because the viral covalently closed circular DNA (cccDNA) minichromosome can persist and sustain viral transcription, creating a need for scalable, reporter readouts that facilitate early discovery of cccDNA-modulating agents. Here, we developed two complementary hepatocyte HiBiT reporter models: a replication-competent HBV reporter in HepaRG cells (HepaRG-Hibit16), in which a secreted split-NanoLuc HiBiT signal is linked to cccDNA-associated expression, and a Cre/Lox-based recombinant cccDNA (rcccDNA) reporter in HepG2 cells (HepG2-Rccc1a) that rapidly generates rcccDNA with a matched HiBiT readout. Screening of 1,403 FDA-approved compounds across both models identified 13 concordant, non-cytotoxic hits. Palovarotene, a retinoic acid receptor-γ agonist, was selected as an exemplar concordant hit and reduced HBV antigens, HBV DNA, and cccDNA and inhibited HBV infection in multiple hepatocyte-based in vitro systems without overt cytotoxicity at the tested concentrations. Together, this dual-reporter strategy supports efficient cross-model triage of candidate cccDNA modulators for subsequent orthogonal validation.

Humans↗

PubMed2026

Serological and Molecular Prevalence of HCMV, HCV, HBV and Toxoplasma gondii Co-infection in Treatment-Naive HIV-Infected Individuals.

INTRODUCTION: Co-infections with human cytomegalovirus (HCMV), hepatitis B virus (HBV), hepatitis C virus (HCV), and Toxoplasma gondii (T. gondii) pose clinical challenges in human immunodeficiency virus-1 (HIV-1)-infected individuals by complicating disease progression and management. This study aimed to investigate the serological and molecular prevalence of HCMV, HBV, HCV, and T. gondii co-infections among treatment-naive HIV-infected individuals. METHODS: A cross-sectional study was conducted from March 2022 to August 2024 on 203 treatment- naive HIV-1-infected individuals. Plasma samples were analyzed using ELISA for serological markers and real-time PCR for molecular detection. Statistical analyses were performed to assess demographic and clinical variables associated with co-infections. RESULTS: Among the 203 participants, the prevalence of anti-HCV antibodies, HBsAg, HCMV IgM, and T. gondii IgM was 9.9%, 2.5%, 1.5%, and 0.5%, respectively. Molecular detection confirmed active HBV, HCV, and HCMV infections in 40%, 60%, and 66.7% of seropositive individuals, respectively, while T. gondii DNA was undetected. HCV genotyping revealed subtype 1a as the most common (50%), followed by 3a (37.5%) and 1b (12.5%). DISCUSSION: The findings indicate a moderate prevalence of HBV and HCV co-infections and a low prevalence of HCMV and T. gondii co-infections in treatment-naive HIV patients. CONCLUSION: These results highlight the need for targeted public health interventions, including vaccination and screening strategies, to reduce the risk of co-infections in HIV-infected individuals.

Humans↗

PubMed2026

Development of a cell-based nanoluciferase reporter system for high-throughput screening of HBV cccDNA inhibitors.

Hepatitis B virus (HBV) persistence is sustained by the viral covalently closed circular DNA (cccDNA) minichromosome, which remains a major barrier to curative antiviral therapies. The lack of reliable quantitative cccDNA detection methods and surrogate markers has hindered efforts to target cccDNA in antiviral high-throughput screening (HTS). Here, we established a novel inducible cccDNA-dependent nanoluciferase (NLuc) reporter cell line, designated HepBLE12, by inserting an in-frame 11-amino acid split-NLuc HiBiT tag into the precore (pC) coding region of an HBV transgene. The resulting 1.3-kDa HiBiT tag on pC serves as the detection module of the split NLuc system, generating quantitative luminescence upon high-affinity complementation with the cognate 18-kDa LgBiT subunit in cell lysates. Notably, the HiBiT assay enables direct detection of intracellular HiBiT-pC protein rather than secreted HBeAg, providing a reporter signal more closely linked to cccDNA activity. HepBLE12 cells exhibited inducible and robust viral DNA replication, and the cccDNA-dependent HiBiT signal was validated under diverse experimental conditions that modulate cccDNA formation or transcription. We further miniaturized the assay to a 384-well format and optimized key parameters following standard HTS assay development practices. The assay was successfully automated and demonstrated excellent performance in a multi-day variability study and a pilot screen, with signal-to-background (S/B) ≈ 9, coefficient of variance (CV) < 10%, and average Z-factor value of 0.74, exceeding canonical HTS quality benchmarks. Together, the HepBLE12 cell-based HTS platform provides a robust and practical tool for identifying inhibitors targeting HBV cccDNA.

Hepatitis B virus↗

PubMed1979

Sex differences in response to hepatitis B virus. III. Responses to HBV and sex of donor and recipient in kidney and bone marrow transplantation.

We proposed the hypothesis that there is an antigen on the hepatitis B virus (HBV) that cross-reacts with a male associated antigen to explain four observations: 1) sex differences in the responses to HBV infection, 2) sex differences in the prevalence of chronic liver diseases associated with hepatitis B, 3) the association of parental responses to HBV with the sex ratio (at birth) of their offspring, and 4) the relation of kidney graft survival with the combination of anti-HBs in the recipients and the sex of the organ donor. Patients with aplastic anemia treated with bone marrow transplantation from HLA identical sibling donors were studied to further test this hypothesis and the results provide additional support. Cross reactivity of HBsAg with H-Y antigen, however, has not been demonstrated.

Anemia, Aplastic↗

PubMed1976

Seroepidemiological study of HBV infections in Athens, Greece.

A seroepidemiological survey of a sample-roughly representative by age and sex - of 2744 persons of the Greater Athens area revealed that hepatitis B virus (HBV) infections are highly endemic in Greece. Hepatitis B surface antigen (HBsAg) was detected in 72(2-6%) of them. The subtype was identified in 70 of the 72 carriers, and 69 were ay; the other was ad. Determinant w was present in all 61 that were capable of being typed further, and a23y(w) was twice as common as a11y(w). Antibody to HBsAg (anti-HBs) was found in 514 (18-7%) persons. The prevalence of the HBsAg rose rapidly with age, reaching peak values (5-3%) at 20-29 years, while anti-HBs reached its highest value (42-1%) in older age groups (50-59 years). The frequency of HBsAg was significantly higher in males (3-4%) than in females (1-5%). The percentage of infected persons who become chronic HBsAg carriers (12-3%) was found higher than in other developed populations. It was also found higher in children (25%) than in adults (5-5%) and in males (14-6%) than in females (8-1%). These data indicate that HBV infection in early life is a major risk factor in the development of HBsAg carriers and support the hypothesis that males are more likely to become HBsAg carriers than females.

Adolescent↗

PubMed1979

A large-scale survey on the prevalence of HBeAG and anti-HBe among asymptomatic carriers of HBV. Correlation with sex, age, HBsAG titre and s-GPT value.

During September and October of 1977, a total of 342,407 apparently healthy blood donors were screen for HBsAG by reversed PHA, and 6,342 (1.9%) asymptomatic carriers of HBV were identified. Prevalence of HBeAG and anti-HBe among HBV carriers was tested by our immunodiffusion method after serum samples had been concentrated threefold. The results were evaluated with reference to sex and age of donors, as well as HBsAG titre and s-GPT level in the serum. HBeAG was found slightly but significantly more often in male donors than in female donors (19.1 vs. 16.7%). In contrast, anti-HBe was found less frequently in males than in females (49.6 vs. 53.1%). Frequency of HBeAG decreased, while frequency of anti-HBe increased with age both in male and female carriers. The prevalence of HBeAG increased in parallel with the titre of HBsAG, whereas the prevalence of anti-HBe was approximately reciprocal to it. An abnormally high value of s-GPT (41 KARMEN U/ml or more) was found in 10.0% of the carriers with HBeAG, contrasting with 3.4% of those with anti-HBe.

Acute Disease↗

PubMed1979

A seroepidemiologic study of infection with HAV and HBV in five Pacific Islands.

A batch of 1025 serum samples, obtained from healthy subjects and hospital patients from five Pacific islands (Viti Levu, Funafuti, Niue, Rarotonga and Upolu) were tested for antibody to hepatitis A virus (anti-HAV), hepatitis B surface antigen (HBsAG) and antibody to hepatitis B surface antigen (anti-HBs) by solid phase radioimmunoassay (SPRIA). High frequencies of anti-HAV were observed in each population (Funafuti, 79.9%; Upolu, 81.6%; Viti Levu, 84.3%; Rarotonga, 95.0%; and Niue, 95.2%), and the age-specific prevalence suggested that the majority of infections with this virus had occurred in the first decade of life. Hepatitis B was endemic in each population, although the total infection rates (as measured by the sum of HBsAG and anti-Hbs frequencies) were lower than for hepatitis A. While infections with each virus tended to run in parallel, peak prevalence of anti-HAV was usually reached in the second decade of life and peak prevalence of HBsAg and anti-HBs was not attained until a decade later. The pattern of infection with HBV was similar in each of the groups studied with the exception of Indians living in Viti Levu, among whom unusually low levels of antigen and antibody were demonstrated.

Adolescent↗

PubMed1978