Bacterial translocation markers and toll‐like receptors in biliary atresia following successful portoenterostomy

• Published in: Acta Paediatrica 2023-10, Vol.112 (10), p.2210-2217
• Main Authors: Godbole, Nimish, Kyrönlahti, Antti, Hukkinen, Maria, Pihlajoki, Marjut, Heikinheimo, Markku, Pakarinen, Mikko P.
• Format: Article
• Language: English
• Subjects: Bacterial Translocation; Biliary atresia; Biliary Atresia - surgery; Biomarkers; CD14 antigen; Child; Cholestasis; Fatty acid-binding protein; Fibrosis; Humans; Inflammation; Innate immunity; Interleukin 6; LBP; Lipopolysaccharides; Liver; Liver diseases; Medicin och hälsovetenskap; Pattern recognition receptors; Portoenterostomy, Hepatic - methods; Serum levels; TLR1 protein; TLR4 protein; TLR7; TLR7 protein; TLR9 protein; Toll-like receptors; Toll-Like Receptors - blood; Tumor Necrosis Factor-alpha
• ISSN: 0803-5253; 1651-2227; 1651-2227
• DOI: 10.1111/apa.16893

Aim The gut–liver axis may contribute to pathophysiology of cholestatic liver disorders like biliary atresia (BA) by bacterial translocation (BT). Toll‐like receptors (TLR) are pattern recognition receptors known to activate innate immunity and secretion of inflammatory cytokines. Herein, we examined BT‐associated biomarkers and TLRs in relation to liver injury after successful portoenterostomy (SPE) in BA. Methods Serum levels of lipopolysaccharide‐binding protein (LBP), CD14, LAL, TNF‐α, IL‐6 and FABP2 along with liver expression of TLRs (TLR1, TLR4, TLR7 and TLR9), LBP and CD14 were measured during median 4.9 (1.7–10.6) years follow‐up after SPE in 45 BA patients. Results Serum LBP, CD14, TNF‐α and IL‐6 all increased after SPE whereas LAL and FABP‐2 remained unchanged. Serum LBP correlated positively with CD14 and markers of hepatocyte injury and cholestasis, but not with Metavir fibrosis stage, transcriptional markers for fibrosis (ACTA2) or ductular reaction. Serum CD14 concentration was significantly higher in patients with portal hypertension than without. While liver expression of TLR4 and LBP remained low, TLR7 and TLR1 showed marked BA‐specific increases, and TLR7 correlated with Metavir fibrosis stage and ACTA2. Conclusion BT does not seem to play a significant role in liver injury after SPE in our series of BA patients.