Single-cell landscape of immune cells during the progression from HBV infection to HBV cirrhosis and HBV-associated hepatocellular carcinoma

• DOI: 10.3389/fimmu.2023.1320414
• Publication Date: 2023-12-06T07:54:40Z
• Authors: Qingquan Bai; Runyang Li; Xiao He; Xiaoting Hong; Ying Yan; Zhengyang Zhao; Han Lin; Frank Tacke; Cornelius Engelmann; Tianhui Hu
• Keywords: Liver Cirrhosis; Hepatitis B virus; 0303 health sciences; Carcinoma, Hepatocellular; cirrhosis; Immunology; Liver Neoplasms; Interleukin-18; hepatocellular carcinoma; RC581-607; Hepatitis B; 03 medical and health sciences; Hepatitis B, Chronic; scRNA-seq; Tumor Microenvironment; Immunology and Allergy; Humans; hepatitis B; Immunologic diseases. Allergy; HBV infection

Introduction Immune cells play crucial roles in the development of chronic hepatitis B virus (HBV) infection, leading to cirrhosis and hepatocellular carcinoma (HCC). However, their functions at different disease stages are not fully understood. Methods In this study, we used single-cell RNA sequencing (scRNA-seq) characterize human liver immune microenvironment stages. We analyzed scRNA-seq data from 118,455 obtained livers six healthy individuals, four patients with HBV five cirrhosis, three HBV-associated HCC. Results Our results showed an accumulation scar-associated macrophages during progression, identified two relevant subsets, Macrophage-CD9/IL18 macrophage-CD9/IFI6. expanded infection while macrophage-CD9/IFI6 verified existence Macrophage-CD9/IFI6 using multiplex immunofluorescence staining. also found increase cytotoxic NK Cell-GNLY progression Additionally, proportion CD4 T cell-TNFAIP3, CD8 cell-TNF (effector cells), cell-CD53 increased, Treg decreased cirrhosis. The cell-LAG3 (Exhausted cell) enhanced, cells) Furthermore, GSEA enrichment analyses revealed that MAPK, ERBB, P53 signaling pathways myeloid were gradually inhibited Discussion study provides important insights into changes hepatic environment HBV-related disease, which may help improve management HBV-infected diseases.