431 Galectin-3 as a Biomarker and Potential Therapeutic Target in Biliary Atresia

Abstract

OBJECTIVES/GOALS: Biliary atresia (BA) is a progressive congenital disease that is characterized by periductular inflammation and fibrosis that leads to bile duct destruction and cholestasis in neonates. Galectin-3 (Gal3) plays a key role in inflammation and fibrosis. The aim of this study was to evaluate plasma Gal3 levels in early and late BA. METHODS/STUDY POPULATION: Samples from our institutional Pediatric Liver Biobank were used for this study. Patients were categorized as early BA (at diagnosis), late BA (at liver transplant), early other cholestatic liver disease (CLD), late other CLD, or controls without cholestasis or structural liver disease. Plasma Gal3 levels were measured by standard ELISA. Inflammatory cytokines were measured in a subset of samples using MSD Proinflammatory Panel 1 multiplex ELISA. Liver fibrosis was categorized as none (Ishak or METAVIR 0), mild (Ishak 1-2 or METAVIR 1), moderate (Ishak 3-4 or METAVIR 2-3), and severe (Ishak 5-6 or METAVIR 4) based on histology. Data are presented as median (IQR) and compared using Kruskal-Wallis test. Spearmans correlation was used to assess the relationship between Gal3 and clinical and inflammatory markers. RESULTS/ANTICIPATED RESULTS: Samples from 10 controls, 26 early BA, 24 late BA, 13 early other CLD, and 8 late other CLD patients were used for this study. Gal3 levels in late BA (20.8 [12.4-30.5] ng/mL) and late other CLD (21.8 [16.9 – 27.2] ng/mL) were significantly higher than in controls (10.2 [7.6 – 14.5] ng/mL, p < 0.02) and early BA (11.3 [8.7 – 16.8] ng/mL, p < 0.01), but not significantly different from early other CLD (15.7 [11.9 – 21.4] ng/mL, p > 0.05). Gal3 positively correlated with fibrosis score (rho 0.3, p = 0.01), total bilirubin (rho 0.3, p = 0.002), ALT (rho 0.3, p = 0.01), AST (rho 0.3, p = 0.005), and APRI score (rho 0.3, p = 0.009), and negatively correlated with albumin (rho -0.3, p = 0.01). Out of the 10 cytokine proinflammatory panel, Gal3 was significantly correlated with IL-6 (rho 0.3, p = 0.006). DISCUSSION/SIGNIFICANCE: Gal3 is elevated in late BA and other CLD at time of transplant and correlated with degree of fibrosis, suggesting it may play a role in disease progression to cirrhosis. If targeted in the early disease stage, blocking Gal3 in pediatric cholestatic liver diseases may help delay the progression to cirrhosis and need for transplant.