Multi-omic analysis unveils biological pathways in peripheral immune system associated to minimal hepatic encephalopathy appearance in cirrhotic patients

Patients with liver cirrhosis may develop minimal hepatic encephalopathy (MHE) which affects their quality of life and life span. It has been proposed that a shift in peripheral inflammation triggers the appearance of MHE. However, the mechanisms involved in this immune system shift remain unknown. In this work we studied the broad molecular changes involved in the induction of MHE with the goal of identifying (1) altered genes and pathways in peripheral blood cells associated to the appearance of MHE, (2) serum metabolites and cytokines with modified levels in MHE patients and (3) MHE-regulated immune response processes related to changes in specific serum molecules. We adopted a multi-omic approach to profile the transcriptome, metabolome and a panel of cytokines of blood samples taken from cirrhotic patients with or without MHE. Gene expression was measured in whole blood cells of cirrhotic patients with and without minimal hepatic encephalopathy.

肝硬化患者可能并发轻微肝性脑病（minimal hepatic encephalopathy, MHE），该疾病会损害患者的生活质量并缩短其生存期限。已有研究提出外周炎症状态的失衡是诱发MHE的关键因素，但这一免疫状态转变背后的具体分子机制仍未明确。本研究围绕MHE诱导过程中的广谱分子变化展开系统探究，旨在达成三大研究目标：（1）筛选与MHE发病相关的外周血血细胞差异表达基因及信号通路；（2）鉴定MHE患者血清中表达水平异常的代谢物（metabolite）与细胞因子（cytokine）；（3）揭示受MHE调控、且与特定血清分子变化相关的免疫应答过程。本研究采用多组学联用策略，对伴或不伴MHE的肝硬化患者的血液样本开展转录组（transcriptome）、代谢组（metabolome）及细胞因子谱特征分析。同时，本研究还检测了伴或不伴轻微肝性脑病的肝硬化患者全血细胞的基因表达水平。