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Peripheral and intrahepatic B-cell subsets contribute to HBeAg seroconversion in patients with chronic hepatitis B
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Peripheral and intrahepatic B-cell subsets contribute to HBeAg seroconversion in patients with chronic hepatitis B
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Journal Article
Peripheral and intrahepatic B-cell subsets contribute to HBeAg seroconversion in patients with chronic hepatitis B
2025
Overview
The immunopathogenesis of chronic hepatitis B (CHB) with unclear immune phases hinders functional cure. 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.
Publisher
BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
Subject
/ Analysis
/ Antigens
/ B cells
/ B-Lymphocyte Subsets - immunology
/ Biomedical and Life Sciences
/ Datasets
/ energy
/ Female
/ Genes
/ HBeAg-negative (HBeAg⁻) chronic HBV infection
/ Hepatitis associated antigen
/ Hepatitis B e Antigens - blood
/ Hepatitis B e Antigens - immunology
/ Hepatitis B virus - immunology
/ Hepatitis B, Chronic - immunology
/ Hepatitis B, Chronic - virology
/ Humans
/ Liver
/ Male
/ memory
/ Virology
