Dysfunction of Circulating Polymorphonuclear Leukocytes and Monocytes in Ambulatory Cirrhotics Predicts Patient Outcome.

BACKGROUND: Cirrhosis represents a state of functional immune paresis with increased infection risk.

AIMS: To investigate polymorphonuclear (PMN) leukocyte and monocyte function in ambulatory cirrhotics, and their potential relation with cirrhosis etiology or patient outcome.

METHODS: Consecutive ambulatory cirrhotics without current or recent (<1 month) infection or acute decompensation were prospectively enrolled in 2013 and followed for a median time of 20 months until death, transplant or end of 2014. Oxidative burst and phagocytosis of circulating PMNs and monocytes were investigated at baseline and after in vitro Escherichia coli stimulation. Seventeen healthy blood donors served as controls. Baseline clinical and laboratory data as well as follow-up data on the development of cirrhosis complications, including acute-on-chronic liver failure (ACLF), and bacterial infections were collected.

RESULTS: Sixty patients were included (70 % male, median age 63 years, 52 % with alcoholic cirrhosis). Compared to controls, cirrhotics showed increased resting and stimulated burst as well as reduced phagocytosis of PMNs, and increased stimulated monocyte burst (p < 0.05 for all). Alcoholic etiology was not related to PMN or monocyte dysfunction (p > 0.05 for all). In Cox regression analysis, increased stimulated monocyte and PMN burst were independent predictors of sepsis, severe sepsis and ACLF occurrence. Also, increased stimulated monocyte burst was associated with worse transplant-free survival (p < 0.05 for all).

CONCLUSIONS: Stimulated PMN and monocyte oxidative burst are increased in ambulatory cirrhotics without acute decompensation. In turn, these changes are associated to sepsis and ACLF occurrence.