Journal
JOURNAL OF CLINICAL MEDICINE
Volume 10, Issue 12, Pages -Publisher
MDPI
DOI: 10.3390/jcm10122705
Keywords
biomarker; cholangiocyte; ductular reaction; liver fibrosis; pediatric liver disease
Categories
Funding
- Sigrid Juselius Foundation
- Finnish Pediatric Research Foundation
- Helsinki University Hospital Fund
- Finska Lakaresallskapet M.H.
- University of Helsinki
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This study revealed that IL-8 is overexpressed in the liver and serum of biliary atresia patients, especially during the postoperative period. IL-8 expression is positively correlated with ductular reaction, liver fibrogenesis, and related cellular markers.
Interleukin (IL)-8 (CXCL8), a chemokine involved in neutrophil recruitment, has been implicated in ductular reaction and liver fibrogenesis. We studied liver and serum IL-8 expression in a large biliary atresia (BA) cohort and explored its prognostic and pathophysiological potential. IL-8 expression was assessed in liver utilizing quantitative polymerase chain reaction (qPCR), immunohistochemistry and in situ hybridization and in serum using an enzyme-linked immunosorbent assay, among 115 BA patients, 10 disease controls and 68 normal controls. Results were correlated to portoenterostomy (PE) outcomes, biochemical and histological liver injury, transcriptional markers of fibrosis and cholangiocytes, and expression of other related cytokines. IL-8 was markedly overexpressed in liver and serum of BA patients at PE (n = 88) and in serum samples obtained during postoperative follow-up (n = 40). IL-8 expression in the liver was predominantly in cholangiocytes within areas of ductular reaction. Liver IL-8 mRNA expression correlated positively with its serum concentration, bile ductular proliferation, Metavir fibrosis stage, and transcriptional markers of activated myofibroblasts (ACTA2) and cholangiocytes (KRT19). Taken together, IL-8 may mediate liver injury in BA by promoting ductular reaction and associated liver fibrogenesis. Prognostic value of serum IL-8 to predict native liver survival was limited and confined to the postoperative period after PE.
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