Department of Hepatology, Qilu Hospital of Shandong University, Jinan 250012, China.
Department of Hepatology, Qingdao Sixth People's Hospital, Qingdao 266000, China.
Int Health. 2023 Jan 3;15(1):19-29. doi: 10.1093/inthealth/ihac003.
We aimed to determine whether the methylation status of thymosin β4 (Tβ4) promoter reflects the severity of acute-on-chronic hepatitis B liver failure (ACHBLF) and whether glucocorticoids affect this status.
Fifty-six patients with ACHBLF, 45 with chronic hepatitis B (CHB) and 32 healthy controls (HCs), were retrospectively enrolled. Methylation-specific PCR and real-time PCR were used to detect Tβ4 methylation frequency and mRNA level. The expression of Tβ4 was measured before and after glucocorticoid treatment in patients with ACHBLF. Clinical and laboratory parameters were obtained.
Tβ4 mRNA expression of patients with ACHBLF was lower than in patients with CHB or HCs, but the methylation frequency was higher. Tβ4 promoter methylation frequency was correlated with serum total bilirubin, prothrombin activity and model for end-stage liver disease score. Moreover, Tβ4 promoter methylation frequency decreased and demethylation occurred during glucocorticoid therapy. After glucocorticoid therapy, Tβ4 mRNA expression and liver function were better in patients with low levels of methylation than in those with higher levels. After 90 d, the survival of patients with low levels of methylation was significantly higher than those with high levels.
Patients with ACHBLF who have low levels of Tβ4 methylation may show a more favorable response to glucocorticoid treatment.
本研究旨在探讨胸腺素β4（Tβ4）启动子的甲基化状态是否反映乙型肝炎慢加急性肝衰竭（ACHBLF）的严重程度，以及糖皮质激素是否会影响这一状态。
回顾性纳入 56 例 ACHBLF 患者、45 例慢性乙型肝炎（CHB）患者和 32 例健康对照者（HCs）。采用甲基化特异性 PCR 和实时 PCR 检测 Tβ4 甲基化频率和 mRNA 水平。ACHBLF 患者在接受糖皮质激素治疗前后测量 Tβ4 的表达。收集临床和实验室参数。
ACHBLF 患者的 Tβ4 mRNA 表达低于 CHB 患者或 HCs，但甲基化频率较高。Tβ4 启动子甲基化频率与血清总胆红素、凝血酶原活动度和终末期肝病模型评分相关。此外，在糖皮质激素治疗期间，Tβ4 启动子的甲基化频率降低，出现去甲基化。糖皮质激素治疗后，低甲基化水平患者的 Tβ4 mRNA 表达和肝功能改善优于高甲基化水平患者。90 d 后，低甲基化水平患者的生存率显著高于高甲基化水平患者。
Tβ4 低甲基化的 ACHBLF 患者可能对糖皮质激素治疗有更好的反应。
