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Macrophage Markers Are Poorly Associated With Liver Histology in Children With Nonalcoholic Fatty Liver Disease

Kazankov, Konstantin*,†; Alisi, Anna; Møller, Holger J.§; De Vito, Rita||; Rittig, Søren; Mahler, Birgitte; Nobili, Valerio#,**; Grønbæk, Henning*

Journal of Pediatric Gastroenterology and Nutrition: November 2018 - Volume 67 - Issue 5 - p 635–642
doi: 10.1097/MPG.0000000000002111
Original Articles: Hepatology

Objectives: We have previously demonstrated associations between the macrophage activation marker soluble (s)CD163 and histology of nonalcoholic fatty liver disease (NAFLD) in adults, and elevated sCD163 levels in children with obesity with NAFLD. Macrophage activation has, however, not been investigated in children with biopsy-proven NAFLD, which was the objective of the present study.

Methods: We used in-house enzyme-linked immunosorbent assays to measure sCD163 and the novel macrophage marker soluble mannose receptor (sMR) in a cross-sectional (n = 155) pediatric NAFLD cohort, and a cohort of NAFLD children (n = 36) undergoing a randomized trial by the probiotic VSL#3. We included 56 healthy nonobese children for comparison.

Results: Levels of sCD163 and sMR were higher in both of the NAFLD cohorts compared with controls (P < 0.001). In the cross-sectional cohort, sCD163 only showed trends toward association with ballooning (rho = 0.14, P = 0.08) and portal inflammation (rho = 0.17, P = 0.08). sMR showed similar associations with liver histology. In the VSL#3 cohort, sCD163 correlated inversely with steatosis (rho = −0.35, P = 0.04), and lobular (rho = −0.57, P < 0.001) and portal inflammation (rho = −0.38, P = 0.02); sMR was not associated with any histological scores. Neither sCD163 nor sMR changed significantly during intervention, and without association with NAFLD resolution.

Conclusions: The macrophage activation markers sCD163 and sMR showed poor associations with liver histology in 2 different cohorts of children with biopsy-proven NAFLD, and none of the markers decreased during successful intervention. These results are in contrast with studies of adult NAFLD and may suggest a possibility of different roles for macrophages in the pathogenesis of adult and pediatric NAFLD.

*Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus N

Department of Internal Medicine, Randers Regional Hospital, Randers, Denmark

Molecular Genetics of Complex Phenotypes, “Bambino Gesù” Children's Hospital, IRCCS, Rome, Italy

§Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus N, Denmark

||Unit of Pathology, ‘Bambino Gesù’ Children's Hospital, IRCCS, Rome, Italy

Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus N, Denmark

#Hepatology, Gastroenterology and Nutrition, “Bambino Gesù” Children's Hospital, IRCCS

**Pediatric Department, University La Sapienza Rome, Rome, Italy.

Address correspondence and reprint requests to Konstantin Kazankov, MD, PhD, Department of Hepatology and Gastroenterology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, DK-8200 Aarhus N, Denmark (e-mail:

Received 23 March, 2018

Accepted 14 July, 2018

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The study was supported by the Danish Council for Strategic Research Funding (TRAIN 092797). H.G. received funding from the NOVO Nordisk Foundation, “Savværksejer Jeppe Juhl og hustru Ovita Juhls mindelegat.” No funding source had any involvement in study design, the collection, analysis, and interpretation of data, in the writing of the report or in the decision to submit the article for publication.

© 2018 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,