Department of Hepatology, Qilu Hospital of Shandong University, Jinan 250012, PR China.
Department of Hepatology, Qilu Hospital of Shandong University, Jinan 250012, PR China; Institute of Hepatology, Shandong University, Jinan 250012, PR China.
Int Immunopharmacol. 2024 Sep 30;139:112686. doi: 10.1016/j.intimp.2024.112686. Epub 2024 Jul 25.
Chronic hepatitis B (CHB) virus infection remains a major public health concern. In this study, the diagnostic capability of C-X-C chemokine receptor type 4 promoter methylation in patients with CHB-associated liver fibrosis/cirrhosis was evaluated.
Two hundred participants were recruited, including 25 healthy controls (HCs), 60 patients with CHB and 115 patients with hepatitis B virus (HBV)-related liver fibrosis/LC. Researchers monitored the methylation and messenger ribonucleic acid (mRNA) levels of C-X-C chemokine receptor type 4 (CXCR4) in peripheral blood mononuclear cells (PBMCs). In addition, we utilized single cell sequencing to analyze the cell types highly expressing CXCR4 in HBV-related liver fibrosis/LC.
HBV-related fibrosis/cirrhosis patients exhibited a significant elevation in the expression level of CXCR4 mRNA in PBMCs compared to CHB ones. The CXCR4 promoter showed a significantly lower methylation level in patients with CHB-related fibrosis/cirrhosis than in patients with CHB. Additionally, the diagnostic area under the area under the curve (AUC) of methylation of the CXCR4 promoter for CHB -related liver fibrosis/LC exceeded liver stiffness measurement (LSM), aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 score (FIB-4). Furthermore, single-cell analysis demonstrated that CXCR4 expression is closely associated with Natural Killer cells(NK cells), T lymphocytes (T cells), and monocytes.
The low methylation of the CXCR4 promoter holds promise as a non-invasive biomarker for detecting CHB-associated liver fibrosis/LC.
慢性乙型肝炎（CHB）病毒感染仍是一个主要的公共卫生关注点。本研究旨在评估 C-X-C 趋化因子受体 4 启动子甲基化在 CHB 相关肝纤维化/肝硬化患者中的诊断能力。
共招募了 200 名参与者，包括 25 名健康对照（HC）、60 名 CHB 患者和 115 名乙型肝炎病毒（HBV）相关肝纤维化/LC 患者。研究人员监测了外周血单个核细胞（PBMC）中 C-X-C 趋化因子受体 4（CXCR4）的甲基化和信使核糖核酸（mRNA）水平。此外，我们利用单细胞测序分析了 HBV 相关肝纤维化/LC 中高表达 CXCR4 的细胞类型。
HBV 相关纤维化/肝硬化患者的 PBMCs 中 CXCR4 mRNA 的表达水平明显高于 CHB 患者。CHB 相关纤维化/肝硬化患者的 CXCR4 启动子甲基化水平明显低于 CHB 患者。此外，CXCR4 启动子甲基化对 CHB 相关肝纤维化/LC 的诊断曲线下面积（AUC）大于肝硬度测量（LSM）、天冬氨酸氨基转移酶-血小板比值指数（APRI）和纤维化-4 评分（FIB-4）。此外，单细胞分析表明，CXCR4 表达与自然杀伤细胞（NK 细胞）、T 淋巴细胞（T 细胞）和单核细胞密切相关。
CXCR4 启动子的低甲基化有望成为一种非侵入性生物标志物，用于检测 CHB 相关肝纤维化/LC。
