Unraveling the Pathogenesis and Etiology of Biliary Atresia

IKK1 and IKK2 cooperate to maintain bile duct integrity in the liver

“…Second, we show that the combined ablation of IKK1-specific functions, most probably related to the regulation of tight junctions in biliary epithelial cells, and of canonical NF-B signaling in the liver causes a destructive bile duct disease and severe cholangitis. The mechanisms regulating the development of cholangitis and cholestasis during chronic hepatitis and the genetic pathways modulating bile duct integrity in the liver remain poorly understood (2,24). Our results point toward a potential role of IKK1 in human bile duct disease and substantiate genetic analysis in patients with cholangitis or biliary atresia for mutations in the CHUK/IKK1 gene.…”

“…Since inhibition of canonical NF-B signaling in NEMO LPC-KO mice results in chronic liver disease characterized by increased hepatocyte apoptosis, liver inflammation and increased expression of TNF and other cytokines (8), it is likely that inflammation is an essential pathogenic component for the development of cholangitis in these mice. Indeed, infiltration of activated immune cells such as macrophages and lymphocytes in the liver has been suggested to be a priming event for bile duct injury and obstruction in humans (24). Furthermore, it has been shown that TNF disrupts the barrier function of cholangiocytes (25).…”

Corticosteroid treatment in biliary atresia: Tonic or toast?

“…1). 5 In the liver and bile ducts of infants with BA, a T helper 1 T-cell response is the predominant inflammatory mechanism, 5 with interferon-␥ and tumor necrosis factor-␣ playing critical roles. There is evidence supporting both CD-4 and CD-8 T-cell-mediated bile duct injury.…”

Case Report of Infantile Cholestasis with Liver Hemangioma

“…Liver enzymes ALT, AST, alkaline phosphatase, and GGT are included in the evaluation, although none is capable of diagnosing a particular condition. Protime/INR and albumin are tests of hepatic protein synthetic function [1][2][3][4][5][6][7][8][9][10].…”

“…Early recognition of cholestasis in infants and prompt diagnosis of the underlying disorder are imperative to identify those disorders that respond to specific treatment. It is therefore recommended that any jaundiced infant have total and direct bilirubin checked at 2 to 3 weeks of age [1][2][3][4][5][6][7].…”