Claudin-3, Lipopolysaccharide Binding Protein, and Jaundice Clearance in Infants with Biliary Atresia.

Abstract

To explore the relationship among bacterial translocation, intestinal barrier integrity, and systemic inflammation in early biliary atresia (BA). Newly diagnosed infants with BA were assessed longitudinally before as well as 6, 12, and 24 weeks after undergoing Kasai portoenterostomy. Plasma immune marker measurement included interleukin (IL)-2, interferon-gamma (IFNγ), IL-4, IL-10, tumor necrosis factor alpha, IL-6, IL-8, IL-1β, IL-17, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Bacterial translocation (lipopolysaccharide binding protein [LBP]; D-lactate), intestinal barrier (claudin-3; intestinal fatty acid binding protein [IFABP], fecal calprotectin) biomarkers, and fecal microbiota genus abundance were analyzed. Fifty-five infants were included, of whom 60% cleared their jaundice. Early post-Kasai, upregulation of plasma adhesion molecules and pro-inflammatory cytokines were associated with poorer jaundice clearance and liver fibrosis and correlated with jaundice severity. Elevated claudin-3 early post-Kasai was associated with poor jaundice clearance [OR 1.02 (1.00, 1.04); P = .02] and jaundice severity [P < .01]. On multivariable analysis, early ICAM-1 elevation (OR 1.008 [1.002, 1.014]; P = .01) and claudin-3 (OR 1.038 [1.009, 1.068]; P = .02), represented independent prognostic markers for persistent jaundice. Increased longitudinal trends of LBP (OR 0.79 [0.71, 0.89]; P < .01) and IFABP (OR <0.01 [2.4E-43, 0.24]; P = .04) were associated with poor jaundice clearance. LBP positively correlated with pro-inflammatory-cytokines (IL-6, P < .01: TNFα, P < .01) and ICAM-1 (P < .01) early post-Kasai. Fecal calprotectin positively correlated with jaundice severity (P < .01) by 24 weeks post-Kasai. No correlation between fecal microbiota abundance and bacterial translocation/intestinal integrity markers was demonstrated. Bacterial translocation may be linked to post-Kasai BA-immune pathways. Claudin-3 could represent a novel biomarker of early intestinal permeability in BA; links to the gut microbiota need further exploration.