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PubMed2025

ANXA3 hypomethylation as a prognostic biomarker in hepatitis B virus-related acute-on-chronic liver failure.

BACKGROUND: Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is associated with a poor prognosis. This research aimed to characterize the expression pattern and clinical value of Annexin A3 (ANXA3) in HBV-ACLF patients. METHODS: First of all, ACLF-related datasets were downloaded from the Gene Expression Omnibus (GEO) database to carry out bioinformatics analyses. RT-qPCR, ELISA, and Methylight were used to measure ANXA3 gene expression and promoter methylation levels. A validation cohort was leveraged to further validate the results. RESULTS: Transcriptome analysis showed that ANXA3 was among the most differentially expressed genes when comparing dead patients with HBV-ACLF to those with survivors. The mRNA and serum levels of ANXA3 were elevated, and methylation levels were decreased in HBV-ACLF patients. The PMR value of ANXA3 in patients with HBV-ACLF was negatively correlated with inflammation-related cytokines IL-6, TNF-α, and IL-1β, as well as quantitative clinical parameters AST, TBIL, PT, INR, NEUT%, and MELD score, and positively correlated with PTA (all p < 0.05). In HBV-ACLF patients, ANXA3 was considered to be an independent influence factor for the 90-day mortality. It was also found that ANXA3, especially hypomethylation, was associated with 28- and 90-day overall survival in patients with HBV-ACLF based on receiver operating characteristic (ROC) analysis, decision curve analysis (DCA), and Kaplan-Meier curves. CONCLUSIONS: ANXA3 hypomethylation has a prominent predictive value for short-term mortality in patients with HBV-ACLF and may serve as a promising biomarker of HBV-ACLF prognosis.

Humans↗

PubMed2026

ICAM-1 Hypomethylation Predicts Poor Prognosis in Patients With Hepatitis B Virus-Related Acute-on-Chronic Liver Failure.

Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is associated with a high short-term mortality rate. Therefore, early and accurate prognostic prediction is crucial for precise clinical management. This study aims to investigate the expression patterns of intercellular adhesion molecule-1 (ICAM-1) and its predictive value for the short-term prognosis of patients with HBV-ACLF. The Methylight method was used to quantitatively detect ICAM-1 promoter methylation level in peripheral blood mononuclear cells (PMBCs) of 286 participants. Meanwhile, the mRNA and plasma expression levels of ICAM-1 were determined using RT-qPCR and ELISA, respectively. The ICAM-1 promoter methylation levels in PBMCs of HBV-ACLF patients were significantly lower than those in chronic hepatitis B (CHB) patients and healthy controls (HCs), whereas the mRNA and plasma expression levels of ICAM-1 were markedly elevated. The ICAM-1 methylation levels in HBV-ACLF patients correlated with specific clinical parameters. Among HBV-ACLF patients, ICAM-1 methylation levels were significantly lower in the non-survivor groups at both 28 and 90 days. The study further revealed that ICAM-1 methylation level serves as an independent influencing factor for the prognosis of HBV-ACLF patients at 28 and 90 days. Based on ROC curve and Kaplan-Meier curves, ICAM-1 methylation levels demonstrated excellent performance in predicting 28- and 90-day mortality in patients with HBV-ACLF. In conclusion, patients with HBV-ACLF exhibit hypomethylation of the ICAM-1 promoter. The combination of ICAM-1 promoter methylation level and MELD score can effectively enhance the predictive ability for the short-term prognosis of HBV-ACLF patients.

Humans↗