The possible role and clinical implication of myeloid-derived suppressor cells in the peripheral blood of patients with hepatitis B virus-related acute-on-chronic liver failure

Abstract

Objective To explore the possible role and clinical implications of myeloid-derived suppressor cells (MDSC) in the peripheral blood of patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (HBV-ACLF). Methods A total of 25 HBV-ACLF patients were enrolled into HBV-ACLF group, 42 chronic hepatitis B (CHB) patients were enrolled into CHB group, and 18 healthy volunteers were collected as healthy controls (HC). Blood samples were collected from patients and the peripheral blood mononuclear cells (PBMC) were separated. The frequency of MDSC and CD4+ /CD8+ T cells in the three groups were detected by flow cytometry. Patients in HBV-ACLF group were followed up for 8 weeks. Multiple comparisons were conducted among three groups. Spearman rank correlation analysis were used to determine the correlation between MDSC frequencies and CD4+ /CD8+ T cells frequencies, biochemical parameters or virological parameters, and to analyze the correlation between MDSC frequencies and model for end-stage liver disease (MELD) sore in patients with HBV-ACLF. Results MDSC frequencies in PBMC were significantly increased in HBV-ACLF group, and had a gradual increasing trend in HC, CHB and HBV-ACLF groups. Comparisons among three groups showed significant difference (χ2=56.823, P<0. 01). HBV-ACLF patients in middle and advanced stage had a higher frequency of MDSC than that of early stage (t=-3.214, P<0.01). MDSC frequencies were positively correlated with alanine aminotransferase (ALT) and total bilirubin (TBil) levels (r=0.455, P<0.01 and r=1.743, P<0.01), but negatively correlated with CD4+ /CD8+ T cells frequencies (r=-0.345, P<0.05 and r=-0.460, P<0.01), albumin (r=-0.612, P<0.01) and prothrombin activity levels (r=-0.673, P<0.01). MDSC frequencies in patients with HBV-ACLF was positively correlated with MELD scores (r=0.541, P<0.01). MDSC frequency was associated with short-term (4 weeks) mortality (56% vs 44%, t=2.262, P<0.05) and the occurrence of ascites (t=2.137, P<0.05) in patients with HBV-ACLF. Conclusion MDSC frequency is associated with disease progression and short-term mortality of HBV-ACLF, and might exert the immunosuppressive effects through inhibiting T-cell proliferation. Key words: Hepatitis B virus; Hepatitis B, chronic; Acute-on-chronic liver failure; MDSC; Immunosuppression