Galectin-3 in biliary atresia and other pediatric cholestatic liver diseases

AimsBiliary 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.MethodsPlasma 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 enzyme-linked immunoassay. Liver tissue was analyzed with multiplex immunohistochemistry and quantified using whole slide analysis. Statistical comparisons were made using nonparametric testing.ResultsPlasma 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.ConclusionsPlasma 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. Biliary atresia is a congenital disease that leads to cirrhosis in children due to lack of bile flow from the liver. Galectin-3 is a novel biomarker that is increased in more advanced stages of the disease and correlates with other markers of disease severity and inflammation. Galectin-3, therefore, could represent a new therapeutic target to increase transplant-free survival in this patient population.image

Automated summary

This study found that circulating Galectin-3 levels increase with disease progression in children with biliary atresia (BA), and are associated with markers of disease severity and inflammation. Late-stage BA is characterized by an elevated number of Galectin-3 expressing M2 macrophages, which is related to activated hepatic stellate cells and bile duct proliferation.