Evidence map›Paper›PMID 42092282›Full record

ArticleJHEP reports : innovation in hepatology2026

Spatial-quantitative profiling of intrahepatic HBsAg heterogeneity and clustered distribution in chronic HBV infection.

Mingzhu Xu, Ye Zheng, Min Wu, Yuyan Qian, Wei Lu, Pingzhao Zhang, Jiangxia Liu, Fahong Li, Shu Song, Jiming Zhang and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JHEP reports : innovation in hepatology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Mingzhu XuKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, School of Basic Medical Sciences, HuaShan Hospital, Shanghai Medical College Fudan University, Shanghai, China; Shanghai Public Health Clinical Center, Fudan University, Shanghai, China; School of Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
Ye ZhengShanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Min WuShanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Yuyan QianKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, School of Basic Medical Sciences, HuaShan Hospital, Shanghai Medical College Fudan University, Shanghai, China.
Wei LuShanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Pingzhao ZhangDepartment of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Jiangxia LiuKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, School of Basic Medical Sciences, HuaShan Hospital, Shanghai Medical College Fudan University, Shanghai, China.
Fahong LiDepartment of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
Shu SongShanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Jiming ZhangKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, School of Basic Medical Sciences, HuaShan Hospital, Shanghai Medical College Fudan University, Shanghai, China; Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
Xiaonan ZhangFaculty of Science and Technology, University of Canberra, Australia. Electronic address: Xiaonan.Zhang@canberra.edu.au.
Zhanqing ZhangShanghai Public Health Clinical Center, Fudan University, Shanghai, China. Electronic address: doctorzzqsphc@163.com.
Jieliang ChenKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, School of Basic Medical Sciences, HuaShan Hospital, Shanghai Medical College Fudan University, Shanghai, China. Electronic address: jieliangchen@fudan.edu.cn.
Zhenghong YuanKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, School of Basic Medical Sciences, HuaShan Hospital, Shanghai Medical College Fudan University, Shanghai, China. Electronic address: zhyuan@shmu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND &

aimsHepatitis B surface antigen (HBsAg), a hallmark of chronic hepatitis B virus (CHB) infection, is expressed from both covalently closed circular DNA (cccDNA) and integrated HBV DNA. HBsAg exhibits diffuse, scattered, or clustered intrahepatic patterns, yet their variation across disease phases and the relationship to HBV DNA remain unclear.

methodsFormalin-fixed paraffin-embedded sections from 385 treatment-naive patients with CHB were analyzed. The immunofluorescence and enhanced in situ hybridization (IF-ISH) assay was coupled with a whole-slide imaging-based quantitative pipeline to delineate the spatial patterns of HBsAg in the context of viral DNA. Laser capture microdissection isolated HBsAg-positive hepatocytes, followed by HBV-enriched Nanopore sequencing and SMART-seq2 based RNA sequencing.

resultsHBeAg-negative individuals showed more clustered HBsAg-positive hepatocytes than HBeAg-positive individuals (55.1% vs. 34.5%). IF-ISH analysis with enhanced sensitivity for HBV DNA confirmed the general mutually exclusive pattern between HBsAg-rich and HBV DNA-positive hepatocytes, while also revealing a subset of colocalization events, together with phase-specific variations in the subcellular (nuclear vs. cytoplasmic) localization of viral DNA. Clustered HBsAg-rich hepatocytes predominantly exhibited cytoplasmic HBV DNA in patients who were HBeAg-positive (54.4%), whereas nuclear HBV DNA was dominant in patients who were HBeAg-negative (78.8%), harboring transcripts derived from integrant and/or cccDNA.

conclusionsThis study provides quantitative evidence that clustered HBsAg-rich hepatocytes are more prevalent in individuals who are HBeAg-negative and predominantly harbor nuclear-localized HBV DNA originating from integration and/or cccDNA, thereby providing new insights into phase-specific intrahepatic viral heterogeneity and advancing understanding of host-virus interactions in HBV persistence. IMPACT AND IMPLICATIONS: This study reveals that clustered HBsAg-positive hepatocytes, enriched in individuals who are HBeAg-negative, predominantly contain nuclear HBV DNA originating from integration and/or cccDNA. The mutually exclusive spatial patterns of HBsAg-rich and HBV DNA-positive hepatocytes reflect distinct viral reservoirs and dynamic changes across different phases of chronic HBV infection. These findings provide new insights into the intrahepatic landscape of HBV persistence and may inform phase-specific strategies for functional cure of chronic hepatitis B.

Indexed as

Hepatitis B, ChronicHepatitis B Surface AntigensHepatitis B virusLiverAdultDNA, ViralFemaleHepatocytesHumansIn Situ HybridizationLaser Capture MicrodissectionMaleMiddle AgedDNA, ViralHepatitis B Surface AntigensHBsAgHBV DNAIn situ hybridizationLaser capture microdissection

Identifiers

PMID42092282
PMCPMC13158402

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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.