Single-cell landscape of immune cells in human livers affected by HBV-related cirrhosis

Qingquan Bai; Xiaoting Hong; Han Lin; Xiao He; Runyang Li; Mohsin Hassan; Hilmar Berger; Frank Tacke; Cornelius Engelmann; Tianhui Hu

doi:10.1016/j.jhepr.2023.100883

Single-cell landscape of immune cells in human livers affected by HBV-related cirrhosis

JHEP Rep. 2023 Aug 18;5(11):100883. doi: 10.1016/j.jhepr.2023.100883. eCollection 2023 Nov.

Authors

Qingquan Bai^{1

2

3}, Xiaoting Hong¹, Han Lin⁴, Xiao He⁵, Runyang Li^{1

2}, Mohsin Hassan³, Hilmar Berger³, Frank Tacke³, Cornelius Engelmann^{3

6

7}, Tianhui Hu^{1

2

8}

Affiliations

¹ Cancer Research Center, School of Medicine, Xiamen University, Xiamen, China.
² National Institute for Data Science in Health and Medicine, Xiamen University, Xiamen, China.
³ Department of Hepatology & Gastroenterology, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, Berlin, Germany.
⁴ Department of Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
⁵ Department of Neurology, The First Affiliated Hospital of Shandong First Medical University, Jinan, China.
⁶ Berlin Institute of Health, Charité-Universitätsmedizin Berlin, Berlin, Germany.
⁷ Institute for Liver and Digestive Health, University College London, Royal Free Campus, London, UK.
⁸ Shenzhen Research Institute, Xiamen University, Shenzhen, China.

Abstract

Background & aims: HBV infection is one of the leading causes of liver cirrhosis. However, the immune microenvironment in patients with HBV cirrhosis remains elusive.

Methods: Single-cell RNA sequencing was used to analyse the transcriptomes of 76,210 immune cells in the livers of six healthy individuals and in five patients with HBV cirrhosis.

Results: Patients with HBV cirrhosis have a unique immune ecosystem characterised by an accumulation of macrophage-CD9/IL18, macrophage-C1QA, NK Cell-JUNB, CD4⁺ T cell-IL7R, and a loss of B cell-IGLC1 clusters. Furthermore, our analysis predicted enhanced cell communication between myeloid cells and all immune cells in patients with HBV-related cirrhosis. Pseudo-time analysis of myeloid cells, natural killer (NK) cells, and B cells demonstrated a significant accumulation of mature cells and a depletion of naive cells in HBV cirrhosis. In addition, we observed an increase in antigen processing and presentation capacities in myeloid cells in patients with HBV cirrhosis, whereas NK cell-mediated cytotoxicity was substantially reduced.

Conclusions: Our results provide valuable insight into the immune landscape of HBV cirrhosis, suggesting that HBV cirrhosis is associated with the accumulation of activated myeloid cells and impaired cytotoxicity in NK cells.

Impact and implications: The absence of single-cell transcriptome profiling of immune cells in HBV cirrhosis hinders our understanding of the underlying mechanisms driving disease progression. To address this knowledge gap, our study unveils a distinctive immune ecosystem in HBV cirrhosis and represents a crucial advancement in elucidating the impact of the immune milieu on the development of this condition. These findings constitute significant strides towards the identification of more effective therapeutic approaches for HBV cirrhosis and are relevant for healthcare professionals, researchers, and pharmaceutical developers dedicated to combating this disease.

Keywords: Cirrhosis; Hepatitis B; Immune cell; Liver; Single-cell RNAseq.