Changes of hepatic myeloid cells in chronic viral hepatitis and after cure and their clinical significance
Authors: Congyun Liu, Cheng Guo, Kai Liu
Journal: Journal of Hepatology (2024)

Single-cell atlas of the liver myeloid compartment before and after cure of chronic viral hepatitisJournal of HepatologyVol. 80Issue 2PreviewChronic viral infections present serious public health challenges; however, direct-acting antivirals (DAAs) are now able to cure nearly all patients infected with hepatitis C virus (HCV), representing the only cure of a human chronic viral infection to date. DAAs provide a valuable opportunity to study immune pathways in the reversal of chronic immune failures in an in vivo human system. Full-Text PDF Open Access Using single-cell RNA sequencing, the article by Cui et al. provides an in-depth phenotypic and functional analysis of hepatic myeloid cells from patients with chronic hepatitis C before and after treatment with direct antiviral drugs, which reveals the changes and regulatory mechanisms of hepatic myeloid cells after chronic infection and cure, and provides valuable information for the understanding of hepatic immunity and for the development of new immune therapies[1]Cui A. Li B. Wallace M.S. et al.Single-cell atlas of the liver myeloid compartment before and after cure of chronic viral hepatitis.J Hepatol. 2024; 80: 251-267https://doi.org/10.1016/j.jhep.2023.02.040Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar. I appreciate the authors' work, but have some questions and suggestions. First, why did the authors choose only patients with hepatitis C for their study and did not include patients with hepatitis B or other chronic viral hepatitis. Hepatitis B is the most common chronic hepatitis worldwide and one of the major risk factors for liver cancer[2]Schweitzer A. Horn J. Mikolajczyk R.T. Krause G. Ott J.J. Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013.Lancet. 2015; 386: 1546-1555https://doi.org/10.1016/S0140-6736(15)61412-XAbstract Full Text Full Text PDF PubMed Scopus (2013) Google Scholar.Whether similar heterogeneity and dynamic changes in hepatic myeloid cells exist in patients with hepatitis B, whether they have different phenotypic and functional characteristics from those of patients with hepatitis C, and whether they respond to and are affected by antiviral therapy differently are all questions worth exploring. The authors should compare the characteristics and differences of hepatic myeloid cells in patients with different types of chronic viral hepatitis in future studies to improve the generalizability and clinical significance of the study. Second, the authors may have overlooked some important cellular markers and functional factors when analyzing subpopulations of hepatic myeloid cells. For example, the authors used only conventional macrophage markers such as CD68 and CD163 when identifying liver macrophages, without taking into account the diversity and plasticity of liver macrophages, as well as the functional differences of different subpopulations [3]Crispe I.N. The liver as a lymphoid organ.Annu Rev Immunol. 2009; 27: 147-163https://doi.org/10.1146/annurev.immunol.021908.132629Crossref PubMed Scopus (773) Google Scholar. Indeed, hepatic macrophages can be divided into two main types: resident Kupffer cells and monocyte-derived macrophages from the peripheral blood. These two types of macrophages are distinctly different in phenotype and function; for example, Kupffer cells mainly express CD68, CD206, and F4/80, whereas monocyte-derived macrophages mainly express CD68, CD163, and CD11b. In addition, hepatic macrophages can be classified into M1 and M2 types based on their polarization status, which are involved in inflammatory responses and tissue In addition, liver macrophages can be divided into M1 and M2 types according to their polarization status, which are involved in inflammatory response and tissue repair, respectively. M1-type macrophages predominantly express CD86, CD80, and TNF-a, whereas M2-type macrophages predominantly express CD206, CD163, and IL-10. I suggest that the authors include these cellular markers and functional factors in subsequent analyses to more accurately portray the subpopulation and functional status of liver macrophages, as well as their changes in response to chronic infection and after healing. Finally, hepatic myeloid cells may play an important role in the development and regression of chronic viral hepatitis, and thus may serve as potential therapeutic targets or prognostic indicators. The authors' study showed that hepatic myeloid cells showed significant phenotypic and functional changes after chronic infection and cure, including downregulation of ISG, upregulation of MHC-II, expression of PD-L1/L2, and expression of IDO1, which may reflect the role of hepatic myeloid cells in antiviral, immunomodulatory, and tissue repair [1]Cui A. Li B. Wallace M.S. et al.Single-cell atlas of the liver myeloid compartment before and after cure of chronic viral hepatitis.J Hepatol. 2024; 80: 251-267https://doi.org/10.1016/j.jhep.2023.02.040Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar. Indeed, several clinical studies have found that the number and activity of hepatic myeloid cells are associated with the severity and prognosis of chronic viral hepatitis. For example, neutrophils and macrophages in the liver can release pro-inflammatory factors and reactive oxygen species, leading to liver inflammation and fibrosis. Myelosuppressive cells in the liver, including neutrophils, monocytes, and macrophages, can inhibit T-cell activation and proliferation through the expression of molecules such as PD-L1/L2, IDO1, and other molecules, thereby affecting viral clearance and autoimmunity. Dendritic cells in the liver can enhance antiviral immunity by expressing molecules such as MHC-II, which promotes T cell differentiation and memory. Thus, hepatic myeloid cells are important players and regulators of chronic viral hepatitis, and can be used as biomarkers for assessing the disease and prognosis, as well as potential targets for improving therapeutic outcomes and preventing complications. In summary, I commend Cui et al. for their study and hope that they will further refine it. Not applicable. Not applicable. Unfunded support.