Alterations in cirRNA Expression Profile during the Development of Acute-on-Chronic Liver Failure Induced by Hepatitis B

Abstract

Background. Hundreds of millions of people worldwide suffer from chronic hepatitis B (CHB), making it one of the most serious public health problems. CHB can lead to serious acute-on-chronic liver failure (ACLF). Since ACLF has a high mortality rate, predicting the risk of ACLF is a critical issue in clinical practice. Methods. To investigate the occurrence of ACLF in CHB, we used high-throughput RNA sequencing to detect the expression of a novel endogenous noncoding RNA (circRNA) in healthy controls (HC) as well as CHB and ACLF patients. Differentially expressed circRNAs were selected and analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway analyses, circRNA-miRNA coexpression networks, and statistical analyses. Results. A total of 21,101 circRNAs were identified in HC, CHB, and ACLF subjects. Compared with the HCs, 4 circRNAs were upregulated and 14 circRNAs were downregulated in ACLF subjects, with a consistent trend in all three groups. GO analysis revealed that regulation of lymphocyte activation and macrophage tolerance induction were the most important biological processes in ACLF progression. KEGG pathway analysis revealed that primary immunodeficiency and NOD-like receptor signaling pathways were the most enriched terms. The circRNA-miRNA coexpression network and statistical analyses showed that circRNA_07734, circRNA_08533, and circRNA_16083 were the most important circRNAs in the process of ACLF. Conclusions. Immune dysfunction and deficiency may play a key role in the development of ACLF, especially circRNA_07734, circRNA_08533, and circRNA_16083.