Pathological neutrophil migration predicts adverse outcomes in hospitalized patients with liver cirrhosis.

BACKGROUND AND AIMS: Given the early response of neutrophil granulocytes to infections, detection of pathological neutrophil migration might help in predicting adverse events in patients with liver cirrhosis.

METHODS: Migration of blood neutrophils in hospitalized patients with cirrhosis was characterized with a novel standardized migration assay. Pathological neutrophil migration patterns were associated with a composite endpoint of ACLF, sepsis or death within 7 or 30 days.

RESULTS: Overall, 125 patients were included, of whom 11 (8.8%) had compensated cirrhosis, 84 (67.2%) had acute decompensation (AD), and 30 (24%) had acute-on-chronic liver failure (ACLF). The migration response of neutrophils from patients with AD or ACLF to stimulation with the chemotactic formylpeptide f-Met-Leu-Phe (fMLP) was significantly impaired, while the response to chemokine (C-X-C motif)-ligand 8 (CXCL8) was affected less pronouncedly. In contrast, no relevant differences in response to CXCL1 were observed. Of note, neutrophils of a number of patients with AD and ACLF were largely immotile at resting and stimulated conditions. Patients with non-migrating neutrophils at unstimulated conditions were at high risk to develop the composite endpoint of ACLF, sepsis or death. Moreover, expression of chemokine receptors CXCR1 and CXCR2 was significantly decreased in patients with ACLF. Interestingly, the expression of chemokine receptors did not correlate with neutrophil migration patterns, but - based on the increased expression of the cell surface markers CD66b and CD177 - neutrophils of patients with AD and ACLF were strongly pre-activated.

CONCLUSION: Pathological neutrophil migration in patients with cirrhosis indicates a high risk of developing adverse outcomes.