Serial circulating markers of inflammation in biliary atresia—Evolution of the post-operative inflammatory process

Abstract

Biliary atresia (BA) may be characterized as an occlusive cholangiopathy affecting both intraand extra-hepatic parts of the biliary tree, together with a pronounced inflammatory response consisting of hepatic infiltration of (predominantly) CD4؉ lymphocytes and macrophages. Soluble cellular adhesion molecules are also known to be raised at the time of portoenterostomy, presumably reflecting intrahepatic disease. We investigated this measur-

Randomized, double-blind, placebo-controlled trial of corticosteroids after Kasai portoenterostomy for biliary atresia

“…22 Increased levels of soluble adhesion molecules are present at the time of portoenterostomy, with a marked increase in a range of proinflammatory cytokines sustained to at least 6 months in some (for example, tumor necrosis factor ␣). 23 Inflammation represents a strong stimulus for the initiation of fibrosis in the liver, and thus the use of anti-inflammatory medications could represent an attractive adjuvant therapy. 24 The anti-inflammatory mechanism of steroids is still imperfectly understood but involves a glucocorticoid (ligand-induced DNA binding protein) receptor and a complex set of protein-protein interactions that lead to transcriptional inhibition of proinflammatory targets.…”

Corticosteroid treatment in biliary atresia: Tonic or toast?

“…7 Abnormal expression of cellular adhesion molecules (intercellular cell adhesion molecule, CD54, vascular cell adhesion molecule, CD62E) on biliary epithelium and vascular endothelium and elevated circulating levels of soluble adhesion molecules have also been observed. 10 Furthermore, a variety of other cytokines, chemokines, and growth factors are released that stimulate downstream amplification of the inflammatory cascade and induction of fibrogenesis (Fig. 1).…”

“…1). Recent data from the King's College group 10 suggest that circulating inflammatory biomarkers (such as soluble intercellular cell adhesion molecule) may also be predictive of clinical response to HPE (need for liver transplant at 1 year of age). Thus, there appears to be a scientific justification for pursuing novel therapies for BA that would target critical inflammatory pathways.…”

The expression of epithelial–mesenchymal transition–related proteins in biliary epithelial cells is associated with liver fibrosis in biliary atresia

“…characterized by ascending obstruction of the biliary tree associated with a progressive sclerosing cholangiopathy (1). The progression of hepatic fibrosis in BA is quite dramatic.…”