Peripheral and intrahepatic B-cell subsets contribute to HBeAg seroconversion in patients with chronic hepatitis B.

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For highly infectious HBeAg-positive (HBeAg+) patients where functional cure is unattainable, achieving sustained HBeAg seroconversion constitutes the key therapeutic objective. This study used single-cell sequencing (scRNA-seq) to analyze B-cell subsets dynamics during HBeAg seroconversion and their roles in restricting HBsAg seroconversion. ScRNA-seq datasets (GSE182159, GSE234241) were retrieved from the GEO database, comprising 67 peripheral blood/liver samples. After batch correction and integration, compared with the two HBeAg+ phases, patients with HBeAg-negative (HBeAg⁻) chronic HBV infection show opposite distribution trends of naive and memory B cells in peripheral blood and liver. Compared with healthy controls and chronic resolved (CR) cases, the HBeAg⁻ chronic HBV infection and HBeAg⁻ groups showed decreased plasma cell proportions in both peripheral blood and liver along with increased hepatic non-switched and switched memory B cells. Functional analysis indicates that B cell subsets in the HBeAg+ group may present more severe metabolic dysfunctions, epigenetic abnormalities, as well as signaling and differentiation defects compared to the HBeAg⁻ group, suggesting a potential pivotal role of B cell subsets in HBeAg seroconversion. Moreover, relative to the CR group, B cell subsets in the HBeAg⁻ group are likely to exhibit more profound energy metabolic impairment and aberrant immune activation, which may consequently facilitate the persistence of HBV infection. B-cell subsets may play a pivotal role in HBeAg seroconversion, and their altered proportions and functional defects may further contribute to the persistence of HBV infection.", "claims": [{"id": "claim-method", "statement": "Differential expression analysis between disease groups for each cell type was performed using the FindMarkers function in Seurat.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41420195", "locator": "sections[6] \"Gene enrichment analysis\" paragraph 2", "quote": "Differential expression analysis between disease groups for each cell type was performed using the FindMarkers function in Seurat."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data can be openly accessed from the GEO public database.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41420195", "locator": "sections[20] \"notes\" paragraph 1", "quote": "The data can be openly accessed from the GEO public database."}], "state": "complete"}, {"id": "claim-target-result", "statement": "B-cell subsets may play a pivotal role in HBeAg seroconversion, and their altered proportions and functional defects may further contribute to the persistence of HBV infection.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:41420195", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "B-cell subsets may play a pivotal role in HBeAg seroconversion, and their altered proportions and functional defects may further contribute to the persistence of HBV infection."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "B-cell subsets may play a pivotal role in HBeAg seroconversion, and their altered proportions and functional defects may further contribute to the persistence of HBV infection.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:41420195"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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