Association of impaired neutrophil migration with adverse outcomes in patients with liver cirrhosis

Introduction Neutrophil granulocytes are the first line defense against bacterial and fungal infections. In the present study, we aimed to determine associations between neutrophil migration capacity and clinical outcome of patients suffering from liver cirrhosis and acute-on-chronic liver failure.

Methods Patients with compensated (n=11), acutely decompensated liver cirrhosis (n=84) or ACLF (n=29) were recruited from a prospective, monocentric cohort study. Peripheral neutrophils were isolated by magnetic beads (Myltenyi biotech). Neutrophil migration was tracked during steady-state-, fMLP-, CXCL1-, or CXCL8-stimulated conditions using time-lapse video microscopy and automated cell tracking. Proportion of migrating cells as well as average migration speed was quantified. Regression analyses were used to determine associations between neutrophil migration and clinical endpoints.

Results The percentage of migrating neutrophils was significantly reduced in patients with acute decompensation (81.32±1.6%, P=0.01) or ACLF (76.63±3.4%, P=0.003) after stimulation with fMLP compared to healthy individuals (89.04±0.8%). Moreover, CXCL8-stimulation was less effective in neutrophils of patients with ACLF (77.56±3.2%) compared to healthy individuals (87.14±2.0%, P=0.04). Average migration speed of neutrophils was decreased after both fMLP- and CXCL8-stimulation in patients with acute decompensation (fMLP 15.23±3.3 µm/min, P=0.001; CXCL8 14.42±0.3 µm/min, P=0.048) or ACLF (fMLP 14.91±0.7 µm/min, P=0.005; CXCL8 13.82±0.4 µm/min, P=0.008) compared to healthy individuals (fMLP 17.78±0.5 µm/min, CXCL8 15.78±0.5 µm/min). A low proportion of migrating neutrophils under steady-state or stimulated conditions was associated with the development of ACLF (P<0.05), sepsis (P<0.05), or the composite of ACLF, sepsis and death (P<0.01) within 7 days.

Conclusion Deficient neutrophil migration under ex vivo steady-state conditions or after stimulation with fMLP or CXCL8 is associated with poor outcome in liver cirrhosis such as the development of sepsis and ACLF. Hence, neutrophil migration analysis might provide as a novel early warning sign for the development of severe complications in liver cirrhosis.

Publication History

Article published online:
09 March 2023