ORIGINAL RESEARCH article
Front. Med.
Sec. Hepatobiliary Diseases
Comparative Single-cell Landscape of Immune Cells in human livers affected HBV and non-viral cirrhosis
Qingquan Bai 1
Zhengyang Zhao 2
Jiashu Zou 3
Chenhao Wang 4
Xiao He 5
Shuqi Mao 1
Su Yongcheng 6
Da Li 7
Bowen Zheng 8
Shengdong Wu 1
Caide Lu 1
Meiya Chen 9
1. Department of Hepatobiliary and Pancreatic Surgery, Ningbo Medical Centre Lihuili Hospital, Ningbo, China
2. Cancer Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, China
3. Department of Hepatic Surgery, First Affiliated Hospital of Harbin Medical University, Harbin, China
4. Department of Gastroenterology, Puyang Oilfield General Hospital, Puyang, China
5. Department of Neurology, Ningbo Medical Centre Lihuili Hospital, Ningbo, China
6. Department of Breast Surgery, The First Affiliated Hospital of Xiamen University, Xiamen, China
7. Department of Gastrology, The First Affiliated Hospital of Tsinghua University, Bei jing, China
8. Cancer Research Center, Xiamen University School of Medicine, Xiamen, China
9. Zhongshan Hospital Xiamen University Department of Gastroenterology, Xiamen, China
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Abstract
Abstract Background Cirrhosis, particularly HBV-induced, poses a significant global health burden. This study compares immune cell landscapes in HBV and non-viral cirrhosis using single-cell RNA sequencing (scRNA-seq) to elucidate distinct immune mechanisms driving disease progression. Methods Liver tissues from HBV cirrhosis patients and healthy controls were analyzed via scRNA-seq. Public single-cell and spatial transcriptomics data were integrated to map immune cell populations. Computational analyses included differential expression, pathway enrichment (KEGG/GO), and cell-cell communication (CellChat). Results HBV cirrhosis exhibited expanded Macrophage-PLCG2 (anti-inflammatory) and CD8+T-FABP5 subsets, while Macrophage-CD5L, CD4+T-ANXA1, CD4+T-CCR6, and NK-FCER1G were reduced. Pathway analysis linked Macrophage-PLCG2 to Rap1 signaling, whereas Macrophage-CD5L associated with lysosomal pathways. Spatial analysis revealed myeloid-T cell colocalization in HBV cirrhosis. Enhanced HLA-E/KLRK1 signaling between myeloid and NK cells was identified in HBV cases (p<0.05). Conclusion This study delineates immune cell heterogeneity between HBV and non-viral cirrhosis, highlighting potential therapeutic targets like Macrophage-PLCG2 and CD8+T-FABP5. Findings underscore the role of immune dysregulation in HBV cirrhosis progression.
Summary
Keywords
cirrhosis, HBV cirrhosis, immune cell landscapes, Non-viral cirrhosis, ScRNA-seq
Received
19 September 2025
Accepted
29 December 2025
Copyright
© 2025 Bai, Zhao, Zou, Wang, He, Mao, Yongcheng, Li, Zheng, Wu, Lu and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Shengdong Wu; Caide Lu; Meiya Chen
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