■微RNA(miRNA)在几种体液中循环,可以是有用的生物标志物。这项研究的目的是鉴定与肝硬化进展和慢性急性肝衰竭(ACLF)相关的血液循环miRNA。
■使用754个miRNA的高通量筛选,来自45例代偿性肝硬化患者的血清样本,失代偿期肝硬化,或ACLF与健康个体(n=15)进行比较。miRNA水平与临床参数相关,器官衰竭,以及疾病进展和结果。在门静脉和肝静脉样本(n=33)中评估了失调的miRNA,肝组织(n=17),和外周血单核细胞(PBMC)(n=16)。
■miRNA筛选分析显示,循环miRNA在肝硬化进展中失调,51miRNA在所有患者组中差异表达。无监督聚类和主成分分析表明,miRNA表达的主要差异发生在失代偿期,失代偿期肝硬化患者和ACLF患者的水平相似。在43个选定的miRNA中,检查了组间的差异,10根据疾病进展差异表达。此外,20个循环miRNA与终末期肝病模型和Child-Pugh评分相关。值得注意的是,11个异常调节的miRNA与肾脏或肝脏衰竭有关,脑病,细菌感染,和糟糕的结果。最严重失调的miRNA(即miR-146a-5p,miR-26a-5p,和miR-191-5p)在门静脉和肝静脉血液和肝组织中进一步评估,但没有差异。然而,来自肝硬化患者的PBMC显示miR-26和miR-146a的显著下调,提示一些循环miRNA的肝外起源。
■本研究是肝硬化进展和ACLF后循环miRNA数据的储存库。在慢性肝病的进展过程中,循环miRNA严重失调,与几个器官的衰竭有关,可能具有预后效用。
■循环miRNA是血液中的小分子,可用于识别或预测临床状况。我们的研究旨在确定miRNA用作肝硬化或慢性急性肝衰竭患者的生物标志物。发现一些miRNA在疾病进展过程中失调,部分患者还与器官衰竭和疾病相关结局有关.
UNASSIGNED: MicroRNAs (miRNAs) circulate in several body fluids and can be useful biomarkers. The aim of this study was to identify blood-circulating miRNAs associated with cirrhosis progression and acute-on-chronic liver failure (ACLF).
UNASSIGNED: Using high-throughput screening of 754 miRNAs, serum samples from 45 patients with compensated cirrhosis, decompensated cirrhosis, or ACLF were compared with those from healthy individuals (n = 15). miRNA levels were correlated with clinical parameters, organ failure, and disease progression and outcome. Dysregulated miRNAs were evaluated in portal and hepatic vein samples (n = 33), liver tissues (n = 17), and peripheral blood mononuclear cells (PBMCs) (n = 16).
UNASSIGNED: miRNA screening analysis revealed that circulating miRNAs are dysregulated in cirrhosis progression, with 51 miRNAs being differentially expressed among all groups of patients. Unsupervised clustering and principal component analysis indicated that the main differences in miRNA expression occurred at decompensation, showing similar levels in patients with decompensated cirrhosis and those with ACLF. Of 43 selected miRNAs examined for differences among groups, 10 were differentially expressed according to disease progression. Moreover, 20 circulating miRNAs were correlated with model for end-stage liver disease and Child-Pugh scores. Notably, 11 dysregulated miRNAs were associated with kidney or liver failure, encephalopathy, bacterial infection, and poor outcomes. The most severely dysregulated miRNAs (i.e. miR-146a-5p, miR-26a-5p, and miR-191-5p) were further evaluated in portal and hepatic vein blood and liver tissue, but showed no differences. However, PBMCs from patients with cirrhosis showed significant downregulation of miR-26 and miR-146a, suggesting a extrahepatic origin of some circulating miRNAs.
UNASSIGNED: This study is a repository of circulating miRNA data following cirrhosis progression and ACLF. Circulating miRNAs were profoundly dysregulated during the progression of chronic liver disease, were associated with failure of several organs and could have prognostic utility.
UNASSIGNED: Circulating miRNAs are small molecules in the blood that can be used to identify or predict a clinical condition. Our study aimed to identify miRNAs for use as biomarkers in patients with cirrhosis or acute-on-chronic liver failure. Several miRNAs were found to be dysregulated during the progression of disease, and some were also related to organ failure and disease-related outcomes.