Characteristics of Peripheral Lymphocyte Subsets in Patients With Acute-On-Chronic Liver Failure Associated With Hepatitis B

Abstract

Background and Aims: Acute-on-chronic liver failure (ACLF) is a rare, but dramatic clinical syndrome. There is substantial evidence suggesting that immunity-mediated inflammation plays an important role in HBV-ACLF. Our aim was to characterize the proportion and cell counts of peripheral blood lymphocyte subsets in acute-on-chronic liver failure patients caused by HBV infection. Methods: One hundred and seventeen patients were enrolled in this study, including those with HBV-related ACLF (HBV-ACLF; n = 70), and HBV related non-ACLF patients (HBV non-ACLF; n = 47). Demographics, clinical and laboratory data at hospital admission were retrospectively analyzed. The percentage and cell count of peripheral lymphocyte subsets were evaluated by flow cytometry. Comparison analysis was performed by t-test or non-parametric Mann-Whitney U-test. Actuarial probabilities of death were calculated by the Kaplan-Meier method. Results: Both circulating lymphocyte count and lymphocyte percentage were significantly reduced in patients with HBV-ACLF (P < 0.001). The CD8⁺ T cell, CD4⁺ T cell, and CD16⁺CD56⁺ NK cell counts were significantly decreased in HBV-ACLF. Consistently, flow cytometric analysis showed that CD8⁺ T cell counts were significantly decreased in non-survivors, while no significant differences were found in CD4⁺ T cell, CD19⁺ B cell, or CD56⁺CD16⁺ NK cell counts. Furthermore, the group with the lower CD8⁺ T cell count displayed a significantly higher mortality rate compared with the group with the higher CD8⁺ T cell count. Conclusions: The abnormal prevalence of lymphocyte subsets may be important in the pathogenesis of HBV-ACLF. The decrease in CD8⁺ T cell counts may be related to poor survival in HBV-ACLF patients.

Keywords: acute-on-chronic liver failure; flow cytometry; hepatitis B virus; immune response; lymphocyte subsets.

Figure 1

Comparison of the proportion of lymphocyte (A), CD3⁺ T cells (B), CD4⁺ T cells (C), CD8⁺ T cells (D), CD19⁺ B cells (E) and CD16⁺CD56⁺ NK cells (F) in patients with hepatitis B-related acute-on-chronic liver failure (ACLF) (n = 70) and non-ACLF (n = 47), where the lines indicated the mean or median. **P < 0.01, ***P < 0.001.

Figure 2

Comparison of cell counts of lymphocyte (A), CD3⁺ T cells (B), CD4⁺ T cells (C), CD8⁺ T cells (D), CD19⁺ B cells (E) and CD16⁺CD56⁺ NK cells (F) in patients with hepatitis B-related acute-on-chronic liver failure (ACLF) (n = 70) and non-ACLF (n = 47), where the lines indicated the mean or median. **P < 0.01, ***P < 0.001.

Figure 3

Comparison of peripheral absolute counts of lymphocyte (A), CD3⁺ T cells (B), CD4⁺ T cells (C), CD8⁺ T cells (D), CD19⁺ B cells (E) and CD16⁺CD56⁺ NK cells (F) in surviving (n = 49) and non-surviving (n = 21) patients with HBV-related ACLF. *P < 0.05, **P < 0.01.

Figure 4

Survival was evaluated using Kaplan–Meier curves, and the statistics were compared by log-rank tests. Significant differences were found between the higher group (CD8⁺ T cell count ≥ 277.95 cells/μl) and the lower group (CD8⁺ T cell count <277.95 cells/μl) in 28-day (chi-square = 6.803, P = 0.009) and 90-day (chi-square = 4.015, P = 0.045) survival.