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

Objective: To explore the relationship among bacterial translocation, intestinal barrier integrity, and systemic inflammation in early biliary atresia (BA). Study design: 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. Results: 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. Conclusions: 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.