SOCS1 methylation level is associated with prognosis in patients with acute-on-chronic hepatitis B liver failure

Abstract

Background: Glucocorticoids could greatly improve the prognosis of patients with acute-on-chronic hepatitis B liver failure (ACHBLF). Suppressor of cytokine signaling (SOCS) 1 methylation has been shown to be associated with mortality in ACHBLF.

Methods: Eighty patients with ACHBLF were divided into group glucocorticoid (GC) and group conservative medical (CM). Sixty patients with chronic hepatitis B (CHB), and Thirty healthy controls (HCs) served as control group. SOCS1 methylation levels in peripheral mononuclear cells (PBMCs) was detected by MethyLight.

Results: SOCS1 methylation levels were significantly higher in patients with ACHBLF than those with CHB and HCs (P < 0.01, respectively). Nonsurvivors showed significantly higher SOCS1 methylation levels (P < 0.05) than survivors in both GC and CM groups in ACHBLF patients. Furthermore, the survival rates of the SOCS1 methylation-negative group were significantly higher than that of the methylation-positive group at 1 month (P = 0.014) and 3 months (P = 0.003) follow-up. Meanwhile, GC group and CM group had significantly lower mortality at 3 months, which may be related to application of glucocorticoid. In the SOCS1 methylation-positive group, the 1-month survival rate was significantly improved, which may be related to GC treatment (P = 0.020). However, no significant difference could be observed between the GC group and CM group in the methylation-negative group (P = 0.190).

Conclusions: GC treatment could decrease the mortality of ACHBLF and SOCS1 methylation levels might serve as prognostic marker for favorable response to glucocorticoid treatment.

Keywords: Acute-on-chronic hepatitis B liver failure; DNA methylation; Glucocorticoid; MethyLight; Prognosis; SOCS1.

Fig. 1

Flowchart for the enrollment of participants

Fig. 2

The SOCS1 methylation levels in different participants groups. SOCS1 methylation level was significantly higher in patients with ACHBLF than in those with CHB (P < 0.01) and HCs group (P < 0.01).

Fig. 3

Associations between SOCS1 promoter methylation level and clinicopathological features in ACHBLF patients A Correlation between PMR value of SOCS1 promoter and TBIL level (Spearman’s r = 0.36, P < 0.01). B Correlation between PMR value of SOCS1 promoter and HBV DNA load (Spearman’s r = − 0.26, P = 0.02). C Correlation between PMR value of SOCS1 promoter and PTA level (Spearman’s r = − 0.32, P < 0.01). D Correlation between PMR value of SOCS1 promoter and PT-INR level (Spearman’s r = 0.29, P = 0.01). E Correlation between PMR value of SOCS1 promoter and MELD score (Spearman’s r = 0.39, P < 0.01). TBIL, total bilirubin; INR, international normalized ratio; PTA, prothrombin time activity; MELD, model for end-stage liver disease

Fig. 4

One and three-month SOCS1 methylation levels analysis in ACHBLF survivors. A The PMR value of SOCS1 promoter in survivors and non-survivors at the end of 1-month. B The PMR value of SOCS1 promoter in survivors and non-survivors at the end of 3-month. GC, glucocorticoid; CM, conservative medical; S, survivors; NS, non-survivors

Fig. 5

Kaplan–Meier curves and Receiver operating characteristic (ROC) curves for SOCS1 methylation level in ACHBLF patients. A Kaplan–Meier curves for the SOCS1 methylation-positive and negative group. B ROC curves of SOCS1 methylation level in predicting 1-month mortality of ACHBLF patients. (c) ROC curves of SOCS1 methylation level in predicting 3-month mortality of ACHBLF patients

Fig. 6

Kaplan–Meier curves for glucocorticoid (GC) and conservative medical management (CM) therapy. A Kaplan–Meier curves for GC and CM therapy. B Kaplan–Meier curves for GC and CM therapy in methylation-positive group. C Kaplan–Meier curves for GC and CM therapy in methylation-negative group