Prognostic role of the stromal cell derived factor-1 in patients with hepatitis B virus-related acute-on-chronic liver failure

Abstract

Background: Stromal cell derived factor-1 (SDF-1) plays a pivotal role in the recruitment of stem cells to injured livers. However, the changes of SDF-l in patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) have yet to be elucidated.

Aim: To study the SDF-1 changes in patients with HBV-related ACLF.

Methods: 30 patients with HBV-related ACLF, 27 patients with chronic hepatitis B and 20 healthy individuals are involved in our study. The SDF-l mRNA expression in liver tissue was detected by quantitative real-time polymerase chain reaction. Immunohistochemical staining was performed to illustrate the expression of SDF-l, CXC receptor 4 (CXCR4) and Ki67. The serum SDF-l concentrations were also detected by enzyme-linked immunosorbent assays.

Results: The expression of SDF-1 mRNA from ACLF patients was remarkably higher than that from other patients (both P < 0.05). The expression of SDF-l, CXCR4 and Ki67 from ACLF were the highest among the three groups (all P < 0.01). The serum SDF-l levels in ACLF patients were significantly lower than that in other patients (both P < 0.01). Moreover, in ACLF patients, the serum SDF-1 Levels were positively correlated with serum total bilirubin and international normalized ratio. In addition, the serum SDF-l levels in survival were significantly lower compared with the non-survivals (P < 0.05). The area under the curve for the serum SDF-1 level in predicting 28-d mortality was 0.722 (P < 0.05).

Conclusion: This study provides the SDF-1 changes in patients with HBV-related ACLF. The SDF-1 Level at admission may serve as a promising prognostic marker for predicting short-term prognosis.

Keywords: Acute-on-chronic liver failure; CXC receptor 4; Hepatitis B; Prognosis; Stromal cell derived factor-1.

Figure 1

Immunohistochemical staining for stromal cell derived factor-1 in livers. Stromal cell derived factor-1 (SDF-1) distribution was extended to bile ductule and hepatic progenitor cells. A: Strongly positive immunostaining in hepatitis B virus-related acute-on-chronic liver failure (ACLF) patients; B: Moderately positive immunostaining in chronic hepatitis B patients; C: Weakly positive immunostaining in healthy controls; D: Comparison of the SDF-1 average absorbance between ACLF group and other groups. A-C: 200 ×. SDF-1: Stromal cell derived factor-1; ACLF: Acute-on-chronic liver failure; CHB: Chronic hepatitis B.

Figure 2

Immunohistochemical staining for CXCR4 in livers. CXCR4 staining was observed predominantly in the membrane and cytoplasm of bile duct epithelium and hepatic progenitor cells. A: Strongly positive immunostaining in hepatitis B virus-related acute-on-chronic liver failure (ACLF) patients; B: Weakly positive immunostaining in chronic hepatitis B patients; C: Negative immunostaining in healthy controls; D: Comparison of the CXCR4 average absorbance between ACLF group and other groups. A-C: 400 ×. CXCR4: CXC receptor 4; ACLF: Acute-on-chronic liver failure; CHB: Chronic hepatitis B.

Figure 3

Immunohistochemical staining for Ki67+ cells in livers. The distribution of Ki67 was predominantly in the portal areas, and minorly in the liver parenchyma. A: Strongly positive immunostaining in hepatitis B virus-related acute-on-chronic liver failure (ACLF) patients; B: Moderately positive immunostaining in chronic hepatitis B patients; C: Weakly positive immunostaining in healthy controls; D: Comparison of the amounts of Ki67+ cells between ACLF group and other groups. A-C: 200 ×. ACLF: Acute-on-chronic liver failure; CHB: Chronic hepatitis B.

Figure 4

Increased serum stromal cell derived factor-1 predicted poor prognosis in hepatitis B virus-related acute-on-chronic liver failure patients. Linear correlation of serum stromal cell derived factor-1 (SDF-1) levels with disease severity marker in acute-on-chronic liver failure (ACLF) patients. SDF-1 was positively correlated with A: Total bilirubin; B: International normalized ratio; C: Non-survivors (n = 19) had elevated SDF-1 levels compared with survivors (n = 11) of patients with hepatitis B virus (HBV)-related ACLF; D: Showed the area under the curve (AUC) of the serum SDF-1 level in predicting 28-d mortality of HBV-related ACLF patients. The AUC was 0.722 (95%CI 0.526-0.919). SDF-1: Stromal cell derived factor-1; TBIL: Total bilirubin; INR: International normalized ratio.