Serum exosomal long non-coding RNA growth arrest-specific 5 predicts 3-month mortality in acute-on-chronic hepatitis B liver failure

Abstract

Abstract Background: Acute-on-chronic hepatitis B liver failure (ACHBLF) is a severe clinical syndrome with high mortality. We aim to evaluate the potential role of serum exosomal long noncoding RNA (lncRNA) growth arrest-specific 5 (GAS5) in ACHBLF and its predictive value for 3-month mortality. Methods: We enrolled 110 patients with ACHBLF and 42 healthy controls (HCs) from December 2017 to June 2022. Exosomes were isolated from the serum of the participants. Serum exosomal lncRNA GAS5 was detected using quantitative real-time polymerase chain reaction. Univariate and multivariate cox proportional hazards regression analysis were used to identify the independent prognostic predictors. The functional role of lncRNA GAS5 on hepatocyte phenotypes was investigated through loss-of-function and gain-of-function assays. Exosomal labeling and cell uptake assay were used to determine the exosomes-mediated transmission of lncRNA GAS5 in hepatocytes. Results: The serum exosomal lncRNA GAS5 was significantly higher in patients with ACHBLF than HCs. It was identified to be an independent predictor for 3-month mortality of ACHBLF. It showed high predictive value for 3-month mortality of ACHBLF and yielded an area under the receiver operating characteristic curve (AUC) value of 0.88, which was markedly higher than MELD score (AUC 0.73; P<0.01). Further study found that lncRNA GAS5 could inhibit hepatocytes proliferation and increase hepatocytes apoptosis. Exosomes-mediated lncRNA GAS5 transfer promoted hepatocytes injury. The knocked down of lncRNA GAS5 weakened H2O2-induced hepatocytes injury. Conclusions: We revealed that serum exosomal lncRNA GAS5 might promote hepatocytes injury and showed high predictive value for 3-month mortality in ACHBLF.