Pathological Neutrophil Migration in Cirrhosis Linked to Increased Risk of AEs

Patients with liver cirrhosis with pathological neutrophil migration may be at higher risk of developing adverse outcomes, according to a study published in Liver International.

“Neutrophils are important effectors in the first-line defense against bacterial and fungal infections, and impaired neutrophil function is considered a major determinant of susceptibility to cirrhosis-associated infections,” the study authors explained. “Given the very early response of neutrophils to infections and autonomous cell migration being a key determinant of infection defense, detection of pathological neutrophil migration might be useful for early prediction of infections and acute-on-chronic liver failure [ACLF] in patients with cirrhosis.”

The authors used a novel, standardized migration assay to identify pathological neutrophil migration patterns—specifically a low proportion and high average speed of migrating neutrophils—in patients hospitalized with liver cirrhosis.

The study included 125 patients. Of this group, 11 (8.8%) patients had compensated cirrhosis, 84 (67.2%) had acute decompensation (AD) without ACLF at admission, and 30 (24%) had ACLF at baseline.

The mean (SD) age was 53.18 (15.54) years for patients with compensated cirrhosis, 54.87 (11.8) years for patients with AD, and 56.7 (10.99) years for patients with ACLF. All 3 subgroups included a majority of male participants.

The authors found that pathological neutrophil migration patterns were associated with a composite end point of ACLF, sepsis, or death within 7 or 30 days.

During 30 days of follow-up, 0 (0%), 6 (7.14%), and 6 (20%) patients with compensated cirrhosis, AD, and ACLF, respectively, died. Additionally, 0 (0%), 3 (3.57%) and 6 (20%) patients, respectively, developed sepsis within 30 days.

Neutrophil migration was quantified in 24 healthy individuals (8 women and 16 men), with a mean (SD) age of 45.1 (14.6) years.

In patients with AD or ACLF, the migration response of neutrophils to stimulation with chemotactic formylpeptide f-Met-Leu-Phe was significantly impaired, while the response to chemokine-ligand 8 was less impaired. However, there were no relevant differences in response to chemokine-ligand 1 observed.

In a number of patients with AD and ACLF, neutrophils were largely immotile at resting and stimulated conditions. Further, patients with nonmigrating neutrophils at unstimulated conditions were at high risk of ACLF, sepsis, or death.

The authors also found 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 preactivated,” the authors said.

According to the authors, this proposed assay is useful in detecting defects in spontaneous migration and migration in response to strong chemoattractants, noting the methods should be further developed to analyze multiple samples at a time. Additionally, a more-developed version of this assay may help manage patients with AD of liver cirrhosis or ACLF before liver transplantation and identify patients who need more immediate treatment.

“Since monitoring of neutrophil migration with the assay proposed here is relatively cost efficient, easy to perform and to standardize between centers, the detection of pathological neutrophil migration may serve as an early warning signal of upcoming adverse events in the future,” the authors concluded.

Reference

Langer MM, Sichelschmidt S, Bauschen A, et al. Pathological neutrophil migration predicts adverse outcomes in hospitalized patients with liver cirrhosis. Liver Int. Published online November 28, 2022. doi:10.1111/liv.15486