The macrophage activation marker sCD163 is associated with morphological disease stages in patients with non-alcoholic fatty liver disease.
Macrophage activation plays a key pathogenic role in experimental non-alcoholic fatty liver disease (NAFLD) and contributes to the progression of steatohepatitis (NASH) and fibrosis. We studied macrophage activation in human NAFLD by measuring soluble (s)CD163, a specific macrophage activation marker, hypothesizing that sCD163 would be associated with the patients' morphological disease grade. Furthermore, we investigated an association between sCD163 and the apoptosis marker cytokeratin-18 (CK-18) to explore a link between macrophage activation and apoptosis.



sCD163 associations with biochemical and histological measures of NAFLD were investigated in two independent cohorts of 157 Australian and 174 Italian NAFLD patients, with liver biopsies graded for NAFLD severity, steatosis and fibrosis. sCD163 and CK-18 were measured by enzyme-linked immunosorbent assay.



In both cohorts sCD163 increased in parallel with the patients' morphological disease grading, being independently associated with the Kleiner fibrosis score (P < 0.001). A high sCD163 predicted advanced fibrosis {F ≥ 3; Australian cohort: area under receiver-operating characteristics curve 0.77 [95% confidence interval (CI): 0.76-0.87], Italian cohort: 0.80 (95% CI: 0.72-0.88)}. In both groups, sCD163 was independently associated with CK-18 (P < 0.001).



Soluble CD163 reflecting macrophage activation is associated with morphological features of NAFLD suggesting their involvement in the pathogenesis of NAFLD, NASH and particularly fibrosis. An independent association between sCD163 and cytokeratin-18 suggests that apoptosis may contribute to macrophage activation in NAFLD/NASH.
Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark. konskaza@rm.dk.
Konstantin
K
Kazankov
The Storr Liver Centre, Westmead Institute for Medical Research, University of Sydney and Westmead Hospital, Westmead, NSW, Australia.|Department of Gastroenterology, Pontificia Universidad Católica, Santiago, Chile.
Francisco
F
Barrera
Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
Holger Jon
HJ
Møller
Division of Gastroenterology and Hepatology, Department of Medical Sciences, University of Torino, Torino, Italy.
Chiara
C
Rosso
Division of Gastroenterology and Hepatology, Department of Medical Sciences, University of Torino, Torino, Italy.
Elisabetta
E
Bugianesi
Division of Pathology, Department of Medical Sciences, University of Torino, Torino, Italy.
Ezio
E
David
Division of Gastroenterology and Hepatology, Department of Medical Sciences, University of Torino, Torino, Italy.
Ramy
R
Younes
The Storr Liver Centre, Westmead Institute for Medical Research, University of Sydney and Westmead Hospital, Westmead, NSW, Australia.
Saeed
S
Esmaili
The Storr Liver Centre, Westmead Institute for Medical Research, University of Sydney and Westmead Hospital, Westmead, NSW, Australia.
Mohammed
M
Eslam
Department of Anatomical Pathology, Institute of Clinical Pathology and Medical Research (ICPMR), Westmead Hospital, Westmead, NSW, Australia.
Duncan
D
McLeod
Department of Biostatistics, Aarhus University, Aarhus, Denmark.
Bo Martin
BM
Bibby
Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
Hendrik
H
Vilstrup
The Storr Liver Centre, Westmead Institute for Medical Research, University of Sydney and Westmead Hospital, Westmead, NSW, Australia.
Jacob
J
George
Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
Henning
H
Grønbaek
D000328:Adult; D015703:Antigens, CD / Q000097:blood*; D015214:Antigens, Differentiation, Myelomonocytic / Q000097:blood*; D017209:Apoptosis; D001315:Australia; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007558:Italy; D053538:Keratin-18 / Q000097:blood*; D016014:Linear Models; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000473:pathology*; D008262:Macrophage Activation; D008264:Macrophages / Q000166:cytology*; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000503:physiopathology*; D012372:ROC Curve; D011956:Receptors, Cell Surface / Q000097:blood*; D000098902:CD163 Antigen
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D000098902:CD163 Antigen; D053538:Keratin-18; D011956:Receptors, Cell Surface
Non-alcoholic steatohepatitis; biomarker; cirrhosis; liver fibrosis; macrophages