Hypermethylation of Thymosin Β4 Predicts a Poor Prognosis for Patients with Acute-on-chronic Hepatitis B Liver Failure.

Background: It has been demonstrated that thymosin beta 4 (T beta 4) 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 beta 4 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 beta 4 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 beta 4 was significantly higher in patients with ACHBLF than in those with pre-ACHBLF, CHB or HCs. However, expression of T beta 4 mRNA showed the opposite trend. In patients with ACHBLF, T beta 4 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 beta 4 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 beta 4 methylation status was better than the model for end-stage liver disease (MELD) score. The predictive value of T beta 4 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 beta 4 methylation might be an important early marker for predicting disease incidence and prognosis in patients with ACHBLF. (c) 2022 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.