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| Hypermethylation of thymosin β4 predicts a poor prognosis for patients with acute-on-chronic hepatitis B liver failure |
| He Wang a , b , Yan-Ping Yin c , Zhen-Li Wang a , Yu Qian a , Yu-Chen Fan a , d , Hui-Hui Liu a , Kai Wang a , d , ∗ |
∗Corresponding author at: Department of Hepatology, Qilu Hospital of Shandong University, #107 Wenhuaxi Road, Jinan 250012, China.
E-mail address: wangdoc876@126.com (K. Wang) . |
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Abstract Background: It has been demonstrated that thymosin β4 (T β4) could inflect the severity of acute-on-chronic hepatitis B liver failure (ACHBLF), but the relationship between its methylation status and the prognosis of liver failure is not clear. This study aimed to determine T β4 promoter methylation status in patients with ACHBLF and to evaluate its prognostic value.
Methods: The study recruited 115 patients with ACHBLF, 80 with acute-on-chronic hepatitis B pre-liver failure (pre-ACHBLF), and 86 with chronic hepatitis B (CHB). In addition, there were 36 healthy controls (HCs) from the Department of Hepatology, Qilu Hospital of Shandong University. The 115 patients with ACHBLF were divided into three subgroups: 33 with early stage ACHBLF (E-ACHBLF), 42 with mid-stage ACHBLF (M-ACHBLF), and 40 with advanced stage ACHBLF (A-ACHBLF). T β4 promoter methylation status in peripheral blood mononuclear cells (PBMCs) was measured by methylation-specific polymerase chain reaction, and mRNA was detected by quantitative real-time polymerase chain reaction.
Results: Methylation frequency of T β4 was significantly higher in patients with ACHBLF than in those with pre-ACHBLF, CHB or HCs. However, expression of T β4 mRNA showed the opposite trend. In patients with ACHBLF, T β4 promoter methylation status correlated negatively with mRNA levels. The 3-month mortality of ACHBLF in the methylated group was significantly higher than that in the unmethylated group. Also, T β4 promoter methylation frequency was lower in survivors than in non-survivors. When used to predict the 1-, 2-, and 3-month incidence of ACHBLF, T β4 methylation status was better than the model for end-stage liver disease (MELD) score. The predictive value of T β4 methylation was higher than that of MELD score for the mortality of patients with E-ACHBLF and M-ACHBLF, but not for A-ACHBLF.
Conclusions: T β4 methylation might be an important early marker for predicting disease incidence and prognosis in patients with ACHBLF.
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2023, Vol. 22 
