thymosin-beta(4) and Acute-On-Chronic-Liver-Failure

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.

Topics: Acute-On-Chronic Liver Failure; End Stage Liver Disease; Glucocorticoids; Hepatitis B, Chronic; Humans; Retrospective Studies; RNA, Messenger; Severity of Illness Index

It has been demonstrated that thymosin β4 (Tβ4) 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 Tβ4 promoter methylation status in patients with ACHBLF and to evaluate its prognostic value.. 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). Tβ4 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.. Methylation frequency of Tβ4 was significantly higher in patients with ACHBLF than in those with pre-ACHBLF, CHB or HCs. However, expression of Tβ4 mRNA showed the opposite trend. In patients with ACHBLF, Tβ4 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, Tβ4 promoter methylation frequency was lower in survivors than in non-survivors. When used to predict the 1-, 2-, and 3-month incidence of ACHBLF, Tβ4 methylation status was better than the model for end-stage liver disease (MELD) score. The predictive value of Tβ4 methylation was higher than that of MELD score for the mortality of patients with E-ACHBLF and M-ACHBLF, but not for A-ACHBLF.. Tβ4 methylation might be an important early marker for predicting disease incidence and prognosis in patients with ACHBLF.

Topics: Acute-On-Chronic Liver Failure; End Stage Liver Disease; Hepatitis B; Hepatitis B, Chronic; Humans; Leukocytes, Mononuclear; Prognosis; Real-Time Polymerase Chain Reaction; RNA, Messenger; Severity of Illness Index; Thymosin

Topics: Acute-On-Chronic Liver Failure; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Humans; Prognosis; Receptors, Cell Surface; Thymosin

In the previous study, we found serum thymosin β4 (Tβ4) levels were associated with mortality in liver failure patients. In this study, we try to evaluate the prognostic value of Tβ4 in acute-on-chronic liver failure (AoCLF) patients by comparing with the Child-Pugh (CTP) and Model for End-Stage Liver Disease (MELD) scores.. Serum Tβ4 levels were measured by enzyme-linked immunosorbent assay (ELISA), and the CTP and MELD scores were calculated for each patient.. Serum Tβ4 levels of AoCLF patients [0.4120 (0.2447-0.7492)μg/mL] were lower than healthy controls [9.2710 (5.1660-13.2485)μg/mL] (P<0.001). AoCLF patients were divided into survival and death group. Compared to survivors, lower Tβ4 concentrations, higher CTP and MELD scores (P<0.001, respectively) were observed in AoCLF patients who died. There were negative correlations between Tβ4 levels and CTP scores (P<0.001), MELD scores (P<0.001). A CTP score of 11.5, a MELD score of 21.63 and a Tβ4 concentration of 0.3840μg/mL were identified as the cut-off values for the stratification of AoCLF patients. MELD≥21.63 combined with Tβ4<0.3840μg/mL can more exactly discriminate between the patients who would survive and die.. Serum Tβ4 concentration has appreciable value to evaluate the short-term prognosis of AoCLF patients, although Tβ4 is not superior to MELD. The combination of Tβ4 and MELD scores are more effective in assessing the prognosis of AoCLF patients.

Topics: Acute-On-Chronic Liver Failure; Biomarkers; Case-Control Studies; Female; Humans; Male; Middle Aged; Predictive Value of Tests; Prognosis; Sensitivity and Specificity; Severity of Illness Index; Thymosin