Infiltration of polarized macrophages associated with liver fibrosis in infants with biliary atresia.

BACKGROUND/PURPOSE: Macrophages exert critical functions in liver homeostasis and have been proposed as potential targets in combatting fibrosis. We aimed to evaluate polarized functional status of liver infiltrated macrophages in infants with biliary atresia (BA).

METHODS

Immunohistochemical staining for CD68, CD163, and IRF5 was performed in 40 BA infants. Liver biopsies were scored for fibrosis and tested for association with clinical biochemical characteristics.

RESULTS

Developing lesions in BA liver progressively accumulated both CD163+ macrophages (M2) and IRF5+ macrophages (M1), while CD163 and IRF5 staining was stronger than the control group (p<0.001). In BA, the higher staining density of CD163 and CD68 was related with elevated serum conjugated bilirubin level (p=0.014 and 0.021, respectively). The CD163/IRF5 macrophages ratio was related with liver fibrosis scores (high vs. low, p=0.004).

CONCLUSIONS

We demonstrated a strong presence of polarized macrophages in BA liver, and macrophage phenotypes were involved in disease development. The balance of different polarized macrophage subpopulations may play a key role in fibrogenesis of BA.