The Immune Landscape of Hepatitis B Virus-Related Acute Liver Failure by Integration Analysis

Abstract

Hepatitis B virus-related acute liver failure (HBV-ALF) is a common type of liver failure, associated with high short-term mortality and morbidity rates. However, the immune landscape of HBV-ALF and its correlation with cell death are currently unknown. Based on 3 Gene Expression Omnibus data sets, infiltrated immune cells were quantified by single-sample gene set enrichment analysis method. The expression levels of immune genes and the abundance of immune cells in liver failure were compared with those in normal liver. The enrichment scores of cell death gene sets from Kyoto Encyclopedia of Genes and Genomes (KEGG) were calculated by gene set variation analysis method, and a protein-protein interaction (PPI) network was constructed using Cytoscape. Besides 21 differentially expressed immune genes, we identified 11 types of differentially infiltrated immune cells in HBV-ALF compared with normal liver. Enriched pathways of these immune genes mainly consisted of chemokine receptors, chemokine binding, interleukin-10 signaling, and TNFs bind their physiological receptors by Reactome pathway analysis. In addition, the enrichment scores of apoptosis and necroptosis pathway instead of autophagy and ferroptosis were increased in liver failure compared with normal liver. PPI network and gene cluster analysis of immune genes and apoptosis and necroptosis genes suggested that hub genes were mainly related to immune response and apoptosis. In summary, our study offers a conceptual framework to understand the immune landscape of HBV-ALF, which might help to improve prognosis.

The necroptosis related gene LGALS3 can be used as a biomarker for the adverse progression from chronic HBV infection to HCC

“…In China, 77% of hepatic fibrosis and 84% of hepatocellular carcinoma cases are caused by HBV ( 1 ). During chronic HBV infection (CHI) progression, the activity of the necroptotic pathway in diseased liver tissues is often enhanced ( 2 ).…”

Comprehensive bioinformatics and machine learning analysis identify VCAN as a novel biomarker of hepatitis B virus-related liver fibrosis

“…In recent years, high-throughput sequencing technologies have provided powerful means for investigating the mechanisms and characteristics of liver disease (Oh et al, 2020;Torres et al, 2020). For example, Gong et al identified that compared with normal liver, there is a unique gene expression pattern for immune response, necroptosis, and apoptosis in liver samples of HBV-related acute liver failure (Gong et al, 2022). Based on bioinformatics analyses, many pivotal genes that are essential for liver disease have been identified.…”

MAIT cells predict long-term prognosis in liver failure patients

“…Chronic stimulation of both innate and adaptive immune cells contributes to this process. [7] Innate immune cells can be activated by cytokines, bacteria, and endotoxins from the gut, which reach the liver via the portal vein, particularly in patients with advanced liver disease. [8] Mucosal-associated invariant T (MAIT) cells are unique innate-like T cells that bridge innate and adaptive immunity.…”