Department of Hepatology, Qilu Hospital of Shandong University, Institute of Shandong University, Wenhuaxi Road 107#, Shandong, Jinan 250012, China.
Department of Infectious Diseases, Qingdao Women and Children Hospital, Qingdao 266034 Shandong, China.
Clin Res Hepatol Gastroenterol. 2016 Sep;40(4):457-64. doi: 10.1016/j.clinre.2015.12.004. Epub 2016 Feb 2.
Tumor necrosis factor-α converting enzyme (TACE) has been demonstrated to be involved in liver inflammation. However, the significance of TACE methylation in acute-on-chronic hepatitis B liver failure (ACHBLF) has not been demonstrated. This study aims to evaluate TACE methylation status in ACHBLF and determine its predictive value for prognosis.
Forty-five patients with ACHBLF, 80 with chronic hepatitis B (CHB) and 54 healthy controls (HCs) were enrolled. The methylation status of TACE promoter was determined by methylation-specific polymerase chain reaction. The TACE mRNA expression was determined by quantitative real-time polymerase chain reaction. The plasma levels of TACE, TNF-α, sTNFRI, sTNFRII were measured by enzyme-linked immunosorbent assay.
TACE methylation was significantly lower in patients with ACHBLF than those with CHB (χ(2)=24.69, P<0.01) and HCs (χ(2)=35.93, P<0.01). Meanwhile, TACE methylation was significantly lower in CHB patients than HCs (χ(2)=4.03, P<0.05). TACE methylation was significantly inversely associated with its mRNA expression (r=-0.68; P<0.01). The plasma levels of TACE, TNF-α, sTNFRI, sTNFRII were significantly higher in patients with ACHBLF than those with CHB (P<0.05, respectively) and HCs (P<0.05, respectively). In patients with ACHBLF, significantly higher prothrombin activity, lower total bilirubin and MELD score were found in TACE methylated group than unmethylated group (P<0.05). ACHBLF patients with methylated TACE showed significantly better survival than those without (P<0.01).
This study showed that demethylation of TACE promoter occurred in ACHBLF and might serve as a potential prognostic marker.
肿瘤坏死因子-α转化酶（TACE）已被证实参与肝脏炎症。然而，TACE 甲基化在乙型肝炎慢加急性肝衰竭（ACHBLF）中的意义尚未得到证实。本研究旨在评估 ACHBLF 中 TACE 甲基化状态，并确定其对预后的预测价值。
纳入 45 例 ACHBLF 患者、80 例慢性乙型肝炎（CHB）患者和 54 名健康对照者（HCs）。采用甲基化特异性聚合酶链反应（PCR）检测 TACE 启动子甲基化状态，实时定量 PCR 检测 TACE mRNA 表达，酶联免疫吸附试验（ELISA）检测 TACE、TNF-α、sTNFRI、sTNFRII 血浆水平。
ACHBLF 患者的 TACE 甲基化水平显著低于 CHB 患者（χ(2)=24.69，P<0.01）和 HCs（χ(2)=35.93，P<0.01）。同时，CHB 患者的 TACE 甲基化水平也显著低于 HCs（χ(2)=4.03，P<0.05）。TACE 甲基化与 mRNA 表达呈显著负相关（r=-0.68；P<0.01）。ACHBLF 患者的 TACE、TNF-α、sTNFRI、sTNFRII 血浆水平显著高于 CHB 患者（P<0.05）和 HCs（P<0.05）。ACHBLF 患者中，TACE 甲基化组的凝血酶原活动度较高，总胆红素和 MELD 评分较低，与未甲基化组相比差异有统计学意义（P<0.05）。TACE 甲基化的 ACHBLF 患者的生存率显著高于未甲基化患者（P<0.01）。
本研究表明，ACHBLF 中发生 TACE 启动子去甲基化，可能作为潜在的预后标志物。
