ArticleJHEP reports : innovation in hepatology2022
Characterization of the liver immune microenvironment in liver biopsies from patients with chronic HBV infection.
Article in JHEP reports : innovation in hepatology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 49 citations in OpenAlex.
- Genomic and transcriptomic features of HBV integration in treatment-naïve, HBeAg-positive children with chronic HBV infection.EBioMedicine · 2026Article
- Review
- A preS2 aa1-26-specific humoural response marks functional cure in chronic HBV infection.EBioMedicine · 2026Article
- Review
- Spatial transcriptional profiling of CHB liver biopsies reveals an undetected population of zonally biased HBV-integrated cells.JHEP reports : innovation in hepatology · 2026Article
- Traditional and Novel Virologic Markers for Functional Cure and HBeAg Loss with Pegylated Interferon in Chronic Hepatitis B: A Systematic Review and Meta-analysis.Journal of clinical and translational hepatology · 2026Article
- Genotype-specific Response to 144-week Entecavir Therapy for HBeAg-positive Chronic Hepatitis B with a Particular Focus on Histological Improvement: A Prospective Study.Journal of clinical and translational hepatology · 2026Article
- The Dual Role of IP-10/CXCL10 in Liver Injury: From Pathogenic Mediator to Clinical Biomarker and Therapeutic Target.Drug design, development and therapy · 2026Review
- Wesselsbron Virus-Induced Hepatitis in Ewes and Lambs Unraveled Through Machine Learning-Driven Digital Histopathology.Transboundary and emerging diseases · 2026Article
- Elevated ALT correlates with severe liver injury, monocyte infiltration, and Pro-inflammatory immune dysregulation in chronic hepatitis B virus infection.Frontiers in medicine · 2026Article
- HBV Suppression by Nucleos(t)ide Analogues Reduces PD-1 Expression on Liver-Resident T Cells.Liver international : official journal of the International Association for the Study of the Liver · 2025Article
- Tertiary Lymphoid Structures Across Organs: Context, Composition, and Clinical Levers.Immunological reviews · 2025Review
- The roles of tertiary lymphoid structures in orchestrating immune responses in peripheral organs.Inflammation and regeneration · 2025Review
- HBV-driven host chromatin accessibility changes affect liver metabolic pathways, iron homeostasis and promote a preneoplastic phenotype.Journal of experimental & clinical cancer research : CR · 2025Article
- Auto-antibodies against interferons are common in people living with chronic hepatitis B virus infection and associate with PegIFNα non-response.JHEP reports : innovation in hepatology · 2025Article
- Aligning cellular and molecular components in age-dependent tertiary lymphoid tissues of kidney and liver.PloS one · 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
- Review
- New dimension in viral hepatitis research.eGastroenterology · 2024Article
- Characterisation of HBV and co-infection with HDV and HIV through spatial transcriptomics.eGastroenterology · 2024Article
Corrections and comments
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Authors and funding
21 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND &
aimsWe aim to describe the liver immune microenvironment by analyzing liver biopsies from patients with chronic HBV infection (CHB). Host immune cell signatures and their corresponding localization were characterized by analyzing the intrahepatic transcriptome in combination with a custom multiplex immunofluorescence panel.
methodMatching FFPE and fresh frozen liver biopsies were collected from immune active patients within the open-label phase IV study GS-US-174-0149. RNA-Seq was conducted on 53 CHB liver biopsies from 46 patients. Twenty-eight of the 53 samples had matched FFPE biopsies and were stained with a 12-plex panel including cell segmentation, immune and viral biomarkers. Corresponding serum samples were screened using the MSD Human V-plex Screen Service to identify peripheral correlates for the immune microenvironment.
resultsUsing unsupervised clustering of the transcriptome, we reveal two unique liver immune signatures classified as immune high and immune low based on the quantification of the liver infiltrate gene signatures. Multiplex immunofluorescence analysis demonstrated large periportal lymphoid aggregates in immune high samples consisting of CD4 and CD8 T cells, B cells and macrophages. Differentiation of the high and low immune microenvironments was independent of HBeAg status and peripheral viral antigen levels. In addition, longitudinal analysis indicates that treatment and normalization of ALT correlates with a decrease in liver immune infiltrate and inflammation. Finally, we screened a panel of peripheral biomarkers and identified ICAM-1 and CXCL10 as biomarkers that strongly correlate with these unique immune microenvironments.
conclusionThese data provide a description of immune phenotypes in patients with CHB and show that immune responses are downregulated in the liver following nucleotide analogue treatment. This may have important implications for both the safety and efficacy of immune modulator programs aimed at HBV cure. LAY SUMMARY: Liver biopsies from patients with chronic hepatitis B were submitted to RNA-Seq and multiplex immunofluorescence and identified two different liver immune microenvironments: immune high and immune low. Immune high patients showed elevated immune pathways, including interferon signaling pathways, and increase presence of immune cells. Longitudinal analysis of biopsies from treatment experienced patients showed that treatment correlates with a marked decrease in inflammation and these findings may have important implications for both safety and efficacy of immune modulator programs for HBV cure.
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