ArticleGut2021
Whole exome HBV DNA integration is independent of the intrahepatic HBV reservoir in HBeAg-negative chronic hepatitis B.
Article in Gut, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
47 citing papers in PubMed, 67 citations in OpenAlex.
- Droplet Digital PCR Measurement of HBV DNA in On-Treatment Chronic HBV Patients: Association With HCC Development and Outcomes.Journal of viral hepatitis · 2026Article
- Spatial-quantitative profiling of intrahepatic HBsAg heterogeneity and clustered distribution in chronic HBV infection.JHEP reports : innovation in hepatology · 2026Article
- Article
- Indeterminate Phase/Grey Zone of Chronic Hepatitis B: Clinical Features, Outcomes and Molecular Insights.Liver international : official journal of the International Association for the Study of the Liver · 2026Review
- Review
- [Reflections on the novel definition and whether or not antiviral therapy for inactive HBsAg carrier state in the "Guidelines for the Prevention and Treatment of Chronic Hepatitis B (version 2022)"].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2025Article
- Mechanisms underlying delayed loss of HBeAg and HBV DNA following HBsAg seroclearance in PEG-IFNα treated patients of chronic hepatitis B.Emerging microbes & infections · 2025Article
- Novel digital droplet inverse PCR assay shows that natural clearance of hepatitis B infection is associated with fewer viral integrations.Emerging microbes & infections · 2025Article
- Navigating the Hepatic Immune Landscape With Fine Needle Aspiration of the Liver-An Emerging Technique.Liver international : official journal of the International Association for the Study of the Liver · 2025Article
- Scientific and medical evidence informing expansion of hepatitis B treatment guidelines.The lancet. Gastroenterology & hepatology · 2025Review
- Profiles of HBV DNA integration in humans with hepatitis B virus infection: Insights for antiviral treatment.JHEP reports : innovation in hepatology · 2025Article
- Genome integration of human DNA oncoviruses.Journal of virology · 2025Review
- Prediction of long-term HBsAg seroclearance in patients with HBeAg-negative chronic hepatitis B.JHEP reports : innovation in hepatology · 2025Article
- HBV sequence integrated to enhancer acting as oncogenic driver epigenetically promotes hepatocellular carcinoma development.Journal of experimental & clinical cancer research : CR · 2025Article
- Development of an NGS-Based Estimation of Integrated HBV DNA in Liver Biopsies and Detection in Liquid Biopsies.Journal of medical virology · 2025Article
- HBV-Induced Carcinogenesis: Mechanisms, Correlation With Viral Suppression, and Implications for Treatment.Liver international : official journal of the International Association for the Study of the Liver · 2025Review
- Pegylated Interferon-α-Induced Functional Cure for Special Populations with Chronic Hepatitis B Virus Infection: Current Trends, Challenges and Prospection.Drug design, development and therapy · 2025Review
- Review
- Integrated DNA estimation in tissue biopsy and detection in liquid biopsy by HBV-targeted NGS assay.medRxiv : the preprint server for health sciences · 2024Article
- Hepatocellular carcinoma among patients with chronic hepatitis B in the indeterminate phase.Journal of viral hepatitis · 2024Review
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
objectiveThe involvement of HBV DNA integration in promoting hepatocarcinogenesis and the extent to which the intrahepatic HBV reservoir modulates liver disease progression remains poorly understood. We examined the intrahepatic HBV reservoir, the occurrence of HBV DNA integration and its impact on the hepatocyte transcriptome in hepatitis B 'e' antigen (HBeAg)-negative chronic hepatitis B (CHB).
designLiver tissue from 84 HBeAg-negative patients with CHB with low (n=12), moderate (n=25) and high (n=47) serum HBV DNA was analysed. Covalently closed circular DNA (cccDNA), pregenomic RNA (pgRNA) were evaluated by quantitative PCR, whole exome and transcriptome sequencing was performed by Illumina, and the burden of HBV DNA integrations was evaluated by digital droplet PCR.
resultsPatients with low and moderate serum HBV DNA displayed comparable intrahepatic cccDNA and pgRNA, significantly lower than in patients with high HBV DNA, while hepatitis B core-related antigen correlated strongly with the intrahepatic HBV reservoir, reflecting cccDNA quantity. Whole exome integration was detected in a significant number of patients (55.6%, 14.3% and 25% in high, moderate and low viraemic patients, respectively), at a frequency ranging from 0.5 to 157 integrations/1000 hepatocytes. Hepatitis B surface antigen >5000 IU/mL predicted integration within the exome and these integrations localised in genes involved in hepatocarcinogenesis, regulation of lipid/drug metabolism and antiviral/inflammatory responses. Transcript levels of specific genes, including the proto-oncogene hRAS, were higher in patients with HBV DNA integration, supporting an underlying oncogenic risk in patients with low-level to moderate-level viraemia.
conclusionsHBV DNA integration occurs across all HBeAg-negative patients with CHB, including those with a limited HBV reservoir; localising in genes involved in carcinogenesis and altering the hepatocyte transcriptome.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.