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Dysfunction of Circulating Polymorphonuclear Leukocytes and Monocytes in Ambulatory Cirrhotics Predicts Patient
Konstantina Sargenti1, Åsa Johansson2,3, Sara Bertilsson4
1Department of Gastroenterology, Skåne University Hospital, University of Lund, 22185, Lund, Sweden. konstantina.sargenti@med.lu.se.
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.
Insights
Cirrhosis patients exhibit heightened immune cell oxidative burst, increasing risks for sepsis and acute-on-chronic liver failure (ACLF). This immune dysfunction is linked to poorer transplant-free survival in individuals with liver cirrhosis.
Area of Science:
- Immunology
- Hepatology
- Infectious Disease
Background:
- Cirrhosis is characterized by impaired immune function, elevating infection susceptibility.
- Ambulatory patients with cirrhosis often present with subclinical immune deficits.
Purpose of the Study:
- To evaluate polymorphonuclear (PMN) leukocyte and monocyte function in ambulatory cirrhotics.
- To determine the relationship between immune cell function, cirrhosis etiology, and patient outcomes.
Main Methods:
- Prospective enrollment of 60 ambulatory cirrhotic patients without recent infection or decompensation.
- Assessment of oxidative burst and phagocytosis in PMNs and monocytes, with in vitro Escherichia coli stimulation.
- Follow-up for development of cirrhosis complications, including acute-on-chronic liver failure (ACLF), and bacterial infections.
Main Results:
- Cirrhotic patients demonstrated increased resting and stimulated PMN oxidative burst and reduced phagocytosis compared to controls.
- Increased stimulated monocyte oxidative burst was observed in cirrhotics.
- Elevated stimulated monocyte and PMN oxidative burst independently predicted sepsis, severe sepsis, and ACLF.
- Increased stimulated monocyte burst correlated with reduced transplant-free survival.
Conclusions:
- Ambulatory cirrhotic patients without acute decompensation show augmented PMN and monocyte oxidative burst.
- These immune alterations are associated with increased incidence of sepsis and ACLF.
- Enhanced oxidative burst in immune cells may serve as a prognostic marker for adverse outcomes in cirrhosis.
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