ArticleThe Journal of clinical investigation2016
In situ analysis of intrahepatic virological events in chronic hepatitis B virus infection.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
58 citing papers in PubMed, 103 citations in OpenAlex.
- Review
- Spatial-quantitative profiling of intrahepatic HBsAg heterogeneity and clustered distribution in chronic HBV infection.JHEP reports : innovation in hepatology · 2026Article
- Spatial transcriptional profiling of CHB liver biopsies reveals an undetected population of zonally biased HBV-integrated cells.JHEP reports : innovation in hepatology · 2026Article
- Review
- Circular nucleic acids at the host-virus interface: from immune modulation to therapeutic innovation.Frontiers in immunology · 2026Review
- C4d Immunoreactivity in Autoimmune and HBV-Induced Hepatitis: Implications for Complement-Mediated Hepatocellular Injury.Pathophysiology : the official journal of the International Society for Pathophysiology · 2025Article
- Review
- Article
- Roles Played by DOCK11, a Guanine Nucleotide Exchange Factor, in HBV Entry and Persistence in Hepatocytes.Viruses · 2024Review
- Article
- A Chromogenic In Situ Hybridization (CISH) Assay for Detection of HBV RNA, DNA, and cccDNA in Liver Tissue.Methods in molecular biology (Clifton, N.J.) · 2024Article
- A case report: cccDNA and pgRNA remain positive in liver tissue in a chronic hepatitis B patient with functional cure.Frontiers in medicine · 2024Article
- A Fluorescent In Situ Hybridization (FISH) Assay for Detection of HBV RNA, DNA, and cccDNA in Cell Culture.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Article
- Intrahepatic quantification of HBV antigens in chronic hepatitis B reveals heterogeneity and treatment-mediated reductions in HBV core-positive cells.JHEP reports : innovation in hepatology · 2023Article
- Nonproductive Hepatitis B Virus Covalently Closed Circular DNA Generates HBx-Related Transcripts from the HBx/Enhancer I Region and Acquires Reactivation by Superinfection in Single Cells.Journal of virology · 2023Article
- Hepatitis B Virus Core Protein Is Not Required for Covalently Closed Circular DNA Transcriptional Regulation.Journal of virology · 2022Article
- A roadmap for serum biomarkers for hepatitis B virus: current status and future outlook.Nature reviews. Gastroenterology & hepatology · 2022Review
- Advances in Immunotherapy for Hepatitis B.Pathogens (Basel, Switzerland) · 2022Review
- Role of hepatitis B virus in development of hepatocellular carcinoma: Focus on covalently closed circular DNA.World journal of hepatology · 2022Review
Corrections and comments
- Commented on by
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Persistent hepatitis B virus (HBV) infection is established by the formation of an intranuclear pool of covalently closed circular DNA (cccDNA) in the liver. Very little is known about the intrahepatic distribution of HBV cccDNA in infected patients, particularly at the single-cell level. Here, we established a highly sensitive and specific ISH assay for the detection of HBV RNA, DNA, and cccDNA. The specificity of our cccDNA probe set was confirmed by its strict intranuclear signal and by a series of Southern blot analyses. Use of our in situ assay in conjunction with IHC or immunofluorescence uncovered a surprisingly mosaic distribution of viral antigens and nucleic acids. Most strikingly, a mutually exclusive pattern was found between HBV surface antigen-positive (HBsA-positive) and HBV DNA- and cccDNA-positive cells. A longitudinal observation of patients over a 1-year period of adeforvir therapy confirmed the persistence of a nuclear reservoir of viral DNA, although cytoplasmic DNA was effectively depleted in these individuals. In conclusion, our method for detecting viral nucleic acids, including cccDNA, with single-cell resolution provides a means for monitoring intrahepatic virological events in chronic HBV infection. More important, our observations unravel the complexity of the HBV life cycle in vivo.
Indexed as
Identifiers
What OpenQuestion holds
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.