Purpose: Recently, an imbalance between subsets of macrophages has been attracting attention as a cause of immune-related liver disease. In this study, we analyzed the localization of macrophage subsets in the liver biopsy specimens of biliary atresia (BA).
Method: This study cohort included 17 liver specimens from BA patients and 15 control liver specimens from autopsy. Liver specimens of BA patients were obtained at Kasai portoenterostomy. As the control, liver histological samples were used, obtained at fresh autopsy from 15 patients (median age: 5 months), which comprised eight patients without clinical or pathological systemic infection and inflammation (normal control: NC group) and seven patients associated with such inflammation (inflammation control: IC group). An immunohistochemical analysis included CD68/CD86 double staining, and double-positive macrophages were defined as M1 and CD68 single-positive macrophages were defined as non-M1. Macrophages were counted in three regions: hepatic lobule, portal area, and interface (IF). These subset populations were investigated in relation to the clinical data and fibrotic area.
Results: In the BA group, M1 macrophages in all regions and non-M1 macrophages in IF and portal areas significantly increased compared to those in the NC group, and it is notable that M1 macrophages often cluster in IF. Non-M1 macrophages in IF showed a significant positive correlation with ALT (r=0.503, p=0.047), D-Bil (r=0.580, p=0.019), and fibrotic areas (r=0.503, p=0.049).
Conclusion: In BA, M1 and non-M1 macrophages were detected as a major population in hepatic lobule and IF, and in portal area and IF, respectively. Non-M1 macrophages in IF were associated with liver fibrosis. This is suspected to be related to the pathogenesis of inflammatory liver fibrosis and obstructive cholestasis in BA.
Keywords: biliary atresia, macrophage, M1
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