ArticleJHEP reports : innovation in hepatology2024
Hepatitis B virus enhancer 1 activates preS1 and preS2 promoters of integrated HBV DNA impairing HBsAg secretion.
Article in JHEP reports : innovation in hepatology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Exploratory analysis of transcriptionally active HBV-host chimeric transcript burden in patients with increasing HBsAg during long-term antiviral therapy.Hepatology international · 2026Article
- Genomic and transcriptomic features of HBV integration in treatment-naïve, HBeAg-positive children with chronic HBV infection.EBioMedicine · 2026Article
- Hepatitis B virus RNA levels and clinical characteristics of persistent viremia in HBsAg-positive patients undergoing nucleos(t)ide analog.Virus research · 2026Article
- Next-step paradigms for Hepatitis B functional cure: insights from the anchor combination therapy trial.Hepatology international · 2026Article
- [Clinical significance and occurrence mechanism of hepatitis B virus DNA integration].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026Review
- Spatial-quantitative profiling of intrahepatic HBsAg heterogeneity and clustered distribution in chronic HBV infection.JHEP reports : innovation in hepatology · 2026Article
- Functional cure for chronic hepatitis B: A state of immune control over cccDNA persistence.Infectious diseases & immunity · 2026Review
- Serum PreS1 antigen combined with vascular endothelial growth factor can identify low-level hepatitis B virus DNA replication in patients with hepatitis B e antigen-negative chronic infection.American journal of translational research · 2026Article
- Research Progress on Mechanisms of Immune Tolerance Induced by Hepatitis B Surface Antigen in Chronic HBV Infection.Journal of immunology research · 2026Review
- Real-world effectiveness of initial antiviral regimens in children with chronic hepatitis B: an age-stratified cohort study.EClinicalMedicine · 2025Article
- Episomal and integrated hepatitis B transcriptome mapping uncovers heterogeneity with the potential for drug-resistance.Nature communications · 2025Article
- Profiles and kinetics of PgRNA and clinical characteristics in pregnant, postpartum, and non-pregnant women with chronic HBV infection.Virology journal · 2025Article
- [The concept of a fountional cure for hepatitis B keeps pace with the times].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2025Article
- Host factor RBM25 promotes HBV replication through Yin Yang 1-mediated cccDNA transcription.Virologica Sinica · 2025Article
- Review
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Authors and funding
18 authors.
Funding
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Abstract
Background & Aims: The expression of HBsAg from integrated HBV DNA limits the achievement of functional cure for chronic hepatitis B. Thus, characterising the unique expression and secretion of HBsAg derived from integrated HBV DNA is of clinical significance. Methods: A total of 563 treatment-naive patients and 62 functionally cured patients were enrolled, and HBsAg and HBcAg immunohistochemistry of their liver biopsy tissues was conducted followed by semi-quantitative analysis. Then, based on stratified analysis of HBeAg-positive and -negative patients, long-read RNA sequencing analysis, as well as an Results: In contrast to the significantly lower serum HBsAg levels, no significant decrease of intrahepatic HBsAg protein was observed in HBeAg-negative patients, as compared with HBeAg-positive patients. The results of long-read RNA sequencing of liver tissues from patients with chronic HBV infection and Conclusions: The secretion of HBsAg originating from integrated HBV DNA was impaired. Mechanistically, functional deficiency of core promoter leads to retargeting of EnhI and thus uneven activation of the SP1 over the SP2 promoter, resulting in an increase in the proportion of L-HBsAg. Impact and implications: Integrated hepatitis B virus (HBV) DNA can serve as an important reservoir for HBV surface antigen (HBsAg) expression, and this limits the achievement of a functional cure. This study revealed that secretion efficiency is lower for HBsAg derived from integrated HBV DNA than HBsAg derived from covalently closed circular DNA, as determined by the unique sequence features of integrated HBV DNA. This study can broaden our understanding of the role of HBV integration and shed new light on antiviral strategies to facilitate a functional cure. We believe our results are of great general interest to a broad audience, including patients and patient organisations, the medical community, academia, the life science industry and the public.
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