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

METHODS: We used in-house ELISAs 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 non-obese 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 towards 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.

CONCLUSION: The macrophage activation markers sCD163 and sMR showed poor associations with liver histology in two 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.