Altered Peripheral Blood Monocyte Phenotype and Function in Chronic Liver Disease: Implications for Hepatic Recruitment and Systemic Inflammation.
OBJECTIVE
Liver and systemic inflammatory factors influence monocyte phenotype and function, which has implications for hepatic recruitment and subsequent inflammatory and fibrogenic responses, as well as host defence.


METHODS
Peripheral blood monocyte surface marker (CD14, CD16, CD163, CSF1R, CCR2, CCR4, CCR5, CXCR3, CXCR4, CX3CR1, HLA-DR, CD62L, SIGLEC-1) expression and capacity for phagocytosis, oxidative burst and LPS-stimulated TNF production were assessed in patients with hepatitis C (HCV) (n = 39) or non-alcoholic fatty liver disease (NAFLD) (n = 34) (classified as non-advanced disease, compensated cirrhosis and decompensated cirrhosis) and healthy controls (n = 11) by flow cytometry.


RESULTS
The selected markers exhibited similar monocyte-subset-specific expression patterns between patients and controls. Monocyte phenotypic signatures differed between NAFLD and HCV patients, with an increased proportion of CD16+ non-classical monocytes in NAFLD, but increased expression of CXCR3 and CXCR4 in HCV. In both cohorts, monocyte CCR2 expression was reduced and CCR4 elevated over controls. CD62L expression was specifically elevated in patients with decompensated cirrhosis and positively correlated with the model-for-end-stage-liver-disease score. Functionally, monocytes from patients with decompensated cirrhosis had equal phagocytic capacity, but displayed features of dysfunction, characterised by lower HLA-DR expression and blunted oxidative responses. Lower monocyte TNF production in response to LPS stimulation correlated with time to death in 7 (46%) of the decompensated patients who died within 8 months of recruitment.


CONCLUSIONS
Chronic HCV and NAFLD differentially affect circulating monocyte phenotype, suggesting specific injury-induced signals may contribute to hepatic monocyte recruitment and systemic activation state. Monocyte function, however, was similarly impaired in patients with both HCV and NAFLD, particularly in advanced disease, which likely contributes to the increased susceptibility to infection in these patients.
Centre for Liver Disease Research, School of Medicine, The University of Queensland, Translational Research Institute, Brisbane, Australia.
Victoria L
VL
Gadd
Centre for Liver Disease Research, School of Medicine, The University of Queensland, Translational Research Institute, Brisbane, Australia.|Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Australia.
Preya J
PJ
Patel
Centre for Liver Disease Research, School of Medicine, The University of Queensland, Translational Research Institute, Brisbane, Australia.
Sara
S
Jose
Centre for Liver Disease Research, School of Medicine, The University of Queensland, Translational Research Institute, Brisbane, Australia.|Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Australia.
Leigh
L
Horsfall
Centre for Liver Disease Research, School of Medicine, The University of Queensland, Translational Research Institute, Brisbane, Australia.|Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Australia.
Elizabeth E
EE
Powell
Centre for Liver Disease Research, School of Medicine, The University of Queensland, Translational Research Institute, Brisbane, Australia.
Katharine M
KM
Irvine
D000328:Adult; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D003937:Diagnosis, Differential; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D019698:Hepatitis C, Chronic / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D006801:Humans; D016130:Immunophenotyping; D007249:Inflammation; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000276:immunology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D065626:Non-alcoholic Fatty Liver Disease / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D010587:Phagocytosis / Q000187:drug effects; D010641:Phenotype; D061251:Primary Cell Culture; D019707:Receptors, Chemokine / Q000235:genetics / Q000276:immunology; D012720:Severity of Illness Index
D015703:Antigens, CD; D015415:Biomarkers; D008070:Lipopolysaccharides; D019707:Receptors, Chemokine