TY - JOUR T1 - PBMC transcriptomics identifies immune-metabolism disorder during the development of HBV-ACLF JF - Gut JO - Gut SP - 163 LP - 175 DO - 10.1136/gutjnl-2020-323395 VL - 71 IS - 1 AU - Jiang Li AU - Xi Liang AU - Jing Jiang AU - Lingling Yang AU - Jiaojiao Xin AU - Dongyan Shi AU - Yingyan Lu AU - Jun Li AU - Keke Ren AU - Hozeifa Mohamed Hassan AU - Jianing Zhang AU - Pengcheng Chen AU - Heng Yao AU - Jiaqi Li AU - Tianzhou Wu AU - Linfeng Jin AU - Ping Ye AU - Tan Li AU - Huafen Zhang AU - Suwan Sun AU - Beibei Guo AU - Xingping Zhou AU - Qun Cai AU - Jiaxian Chen AU - Xiaowei Xu AU - Jianrong Huang AU - Shaorui Hao AU - Jinqiu He AU - Shaojie Xin AU - Di Wang AU - Jonel Trebicka AU - Xin Chen AU - Jun Li A2 - , Y1 - 2022/01/01 UR - http://gut.bmj.com/content/71/1/163.abstract N2 - Objective Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) pathophysiology remains unclear. This study aims to characterise the molecular basis of HBV-ACLF using transcriptomics.Methods Four hundred subjects with HBV-ACLF, acute-on-chronic hepatic dysfunction (ACHD), liver cirrhosis (LC) or chronic hepatitis B (CHB) and normal controls (NC) from a prospective multicentre cohort were studied, and 65 subjects (ACLF, 20; ACHD, 10; LC, 10; CHB, 10; NC, 15) among them underwent mRNA sequencing using peripheral blood mononuclear cells (PBMCs).Results The functional synergy analysis focusing on seven bioprocesses related to the PBMC response and the top 500 differentially expressed genes (DEGs) showed that viral processes were associated with all disease stages. Immune dysregulation, as the most prominent change and disorder triggered by HBV exacerbation, drove CHB or LC to ACHD and ACLF. Metabolic disruption was significant in ACHD and severe in ACLF. The analysis of 62 overlapping DEGs further linked the HBV-based immune-metabolism disorder to ACLF progression. The signatures of interferon-related, neutrophil-related and monocyte-related pathways related to the innate immune response were significantly upregulated. Signatures linked to the adaptive immune response were downregulated. Disruptions of lipid and fatty acid metabolism were observed during ACLF development. External validation of four DEGs underlying the aforementioned molecular mechanism in patients and experimental rats confirmed their specificity and potential as biomarkers for HBV-ACLF pathogenesis.Conclusions This study highlights immune-metabolism disorder triggered by HBV exacerbation as a potential mechanism of HBV-ACLF and may indicate a novel diagnostic and treatment target to reduce HBV-ACLF-related mortality.Data, that is raw reads from RNA-seq experiments in fastq files, are available in a public, open access repository without restrictions on the use or distribution of the data. The Sequence Read Archive database project accession number for accessing the data produced for this study is PRJNA548207 (https://www.ncbi.nlm.nih.gov/bioproject/PRJNA548207/). ER -