Title: Galectin-3 in biliary atresia and other pediatric cholestatic liver diseases
Source: Hepatology Research 2023, Nov 11. [E-publication]
Date of publication: November 2023
Publication type: Article
Abstract: Background & aims: Biliary atresia (BA) is characterized by intrahepatic inflammation and rapid progression of liver fibrosis. Galectin-3, a beta-galactoside binding protein, is a key regulator of inflammation and fibrosis. The aim of this study was to characterize circulating and hepatic Galectin-3 levels in children with BA.
Methods: Plasma and liver samples were obtained from children with early BA at time of Kasai hepatoportoenterostomy, late BA at time of transplant, early and late other cholestatic liver diseases (CLD), and controls. Plasma Galectin-3 was measured using standard ELISA. Liver tissue was analyzed with multiplex immunohistochemistry and quantified using whole slide analysis. Statistical comparisons were made using non-parametric testing.
Results: Plasma Galectin-3 in late BA was significantly higher than in early BA (20.82 [12.45 – 30.46] vs. 11.30 [8.74 – 16.83] ng/ml, p = 0.0096). Galectin-3 levels correlated with markers of disease severity and interleukin-6. There were significantly more Galectin-3+ M2 macrophages in late BA in comparison to late other CLD (162 [157 – 233] vs. 49 [33 – 59] cells/mm2 , p = 0.03). The number of Galectin-3+ M2 macrophages correlated with the number of activated hepatic stellate cells and bile duct proliferation.
Conclusions: Plasma Galectin-3 is higher in late BA at time of transplant in comparison to early BA at time of Kasai. The number of Galectin-3 expressing M2 macrophages in late BA is elevated relative to late other CLD and was associated with other prognostic histological findings. Galectin-3 targeted therapy may be beneficial in slowing disease progression to cirrhosis in children with BA.