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

Jiao Gong,Liuping Sha,Danyang Li,Bo Hu,Yaqiong Chen,Xinhua Li,Yang Wang,Yutian Chong,Jiahao Chen,Jing Cao,Dawei Cui

doi:10.1155/2022/6764379

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.

Highlights

Acute liver failure (ALF), a life-threatening illness, is referred as a clinical syndrome with acute and massive hepatocellular destruction within 4 weeks
protein-protein interaction (PPI) network analysis revealed the enrichment of immune response and apoptosis
We further mined the difference in those abovementioned immune genes and cells between normal liver tissues and samples from Hepatitis B virus (HBV)-related acute liver failure (HBV-ALF) patients

Summary

Introduction

Acute liver failure (ALF), a life-threatening illness, is referred as a clinical syndrome with acute and massive hepatocellular destruction within 4 weeks. The features of ALF include acute development of jaundice, multiple organ failure, and/ or encephalopathy in patients without a history of liver disease [1, 2]. The short-term mortality of ALF can reach up to 40-50%, and the main death causes in patients with ALF are largely ascribed to sepsis with multiple organ failure and cerebral herniation due to increased intracranial pressure [1, 3]. Hepatitis B virus (HBV) is the main cause of ALF in Eastern countries [4]. More than 0.1%-0.5% patients with HBV infection would develop ALF [6, 7]. A comprehensive understanding of the etiology of HBV-ALF, improvement of treatments, and intensive care support will shed more light

Methods

Results

Conclusion