Extrahepatic biliary atresia: A first-trimester event? Clues from light microscopy and immunohistochemistry

Tan, Carolyn E.L.; Driver, Marie; Howard, E. R.; Moscoso, G.

doi:10.1016/0022-3468(94)90377-8

Cited by 107 publications

(64 citation statements)

References 18 publications

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“…Biliary atresia is either syndromic (10% of cases), and if so associated with anomalies (intestinal malrotation, situs inversus, malposition of the spleen, cardiac defect), or nonsyndromic (Chardot, 2006). The etiology of biliary duct atresia is unknown, although various hypotheses have been formulated, such as persistence of fetal bile ducts, which release bile into the hepatic parenchyma, leading to an inflammatory reaction that causes fibrosis (Tan et al, 1994). A viral cause has been posited, but the data are contradictory (Steele et al, 1995), and familial cases suggest that a genetic component may be implicated (Lachaux et al, 1988), but no gene has yet been identified.…”

Section: Discussionmentioning

confidence: 99%

Nonvisualization of the fetal gallbladder by second‐trimester ultrasound scan: strategy of clinical management based on four examples

et al. 2008

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Objective When the fetal gallbladder is not seen at ultrasound (US) scan, to propose a diagnostic method of differentiating fetuses who are healthy or have minor anomalies from fetuses with severe anomalies requiring intensive management. MethodWe present four clinical cases illustrating this variability, together with additional examinations: karyotyping, screening for cystic fibrosis mutations, amniotic fluid digestive enzyme activities. ResultsThe four examples we present-biliary duct atresia, biliary agenesis, gallbladder reveal at birth, and cystic fibrosis-illustrate the difficulties of making both diagnosis and prognosis prenatally when the gallbladder is not visualized. Laboratory assays allowed prenatal management. ConclusionFailure to visualize the gallbladder prenatally may indicate fetal diseases of highly variable prognosis, but may also sometimes be followed by postnatal visualization in a child free of any disease. Prenatal management could help in defining diagnosis and prognosis.

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Section: Discussionmentioning

confidence: 99%

Nonvisualization of the fetal gallbladder by second‐trimester ultrasound scan: strategy of clinical management based on four examples

et al. 2008

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“…6 The cause of biliary atresia is not known. Current theories regarding its pathogenesis include defects in bile duct development, 7 viral infection of the biliary tree, [8][9][10] and immune-mediated bile duct injury. [11][12][13] We hypothesized that the pathogenesis of BA may involve both a primary perinatal hepatobiliary viral infection and secondary generation of an autoreactive T cell-mediated bile duct injury.…”

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confidence: 99%

Cellular and humoral autoimmunity directed at bile duct epithelia in murine biliary atresia

et al. 2006

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Biliary atresia is an inflammatory fibrosclerosing lesion of the bile ducts that leads to biliary cirrhosis and is the most frequent indication for liver transplantation in children. The pathogenesis of biliary atresia is not known; one theory is that of a virus-induced, subsequent autoimmune-mediated injury of bile ducts. The aim of this study was to determine whether autoreactive T cells and autoantibodies specific to bile duct epithelia are present in the rotavirus (RRV)-induced murine model of biliary atresia and whether the T cells are sufficient to result in bile duct inflammation. In vitro analyses showed significant increases in IFN-␥-producing T cells from RRV-diseased mice in response to bile duct epithelial autoantigen. Adoptive transfer of the T cells from RRV-diseased mice into naïve syngeneic SCID recipients resulted in bile duct-specific inflammation. This induction of bile duct pathology occurred in the absence of detectable virus, indicating a definite response to bile duct autoantigens. Furthermore, periductal immunoglobulin deposits and serum antibodies reactive to bile duct epithelial protein were detected in RRV-diseased mice. In conclusion, both cellular and humoral components of autoimmunity exist in murine biliary atresia, and the progressive bile duct injury is due in part to a bile duct epithelia-specific T cell-mediated immune response. The role of cellular and humoral autoimmunity in human biliary atresia and possible interventional strategies therefore should be the focus of future research.

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“…They were further divided into two groups retrospectively according to the clinical features at the end of 12-month follow-up after the Kasai operation: three patients (patients 6-8) who were jaundice free and with good bile flow (BA1) and six patients (patients 9-14) who had jaundice and finally underwent liver transplantation (BA2). In addition, liver tissues were also obtained from six children (Supporting Table 1, patients [15][16][17][18][19][20] with advanced-stage BA at the time of liver transplantation (LT). Near-normal liver tissues were the nontumor parts of surgically removed liver tissues from two patients with colon cancer metastasized to the liver.…”

Section: Methodsmentioning

confidence: 99%

“…15 Striking similarities have been reported between proliferative bile ductules and developing bile ducts in human fetus. 16 Because there are increased numbers of both proliferating ductular cells and newly regenerating hepatocytes in BA livers, 17 it has been suggested that both types of cells may differentiate from HSCs activated in BA livers. 17 Based on these observations, here we explored the mechanisms controlling the activation and differentiation of cells in ductular reactions and their possible relationship to HAI-1 and -2-related ECM remodeling and fibrosis progression in livers with BA or other cholangiopathies.…”

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confidence: 99%

Persistent elevation of hepatocyte growth factor activator inhibitors in cholangiopathies affects liver fibrosis and differentiation

et al. 2011

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Alteration of cell surface proteolysis has been proposed to play a role in liver fibrosis, a grave complication of biliary atresia (BA). In this study we investigated the roles of hepatocyte growth factor activator inhibitor (HAI)-1 and -2 in the progression of BA. The expression levels of HAI-1 and -2 were significantly increased in BA livers compared with those in neonatal hepatitis and correlated with disease progression. In BA livers, HAI-1 and -2 were coexpressed in cells involved in ductular reactions. In other selective cholangiopathies, ductular cells positive for HAI-1 or HAI-2 also increased in number. Inflammatory cytokines, growth factors, and bile acids differentially up-regulated expression of HAI-1 and -2 transcripts in fetal liver cells and this induction could be antagonized by a cyclooxygenase-2 inhibitor. Conditioned media from cell lines stably overexpressing HAI-1 or HAI-2 enhanced the fibrogenic activity of portal fibroblasts and stellate cells, suggesting that both proteins might be involved in liver fibrosis. Because HAI-1 and -2 colocalized in ductular reactions sharing similar features to those observed during normal liver development, we sought to investigate the role of HAI-1 and -2 in cholangiopathies by exploring their functions in fetal liver cells. Knockdown of HAI-1 or HAI-2 promoted bidirectional differentiation of hepatoblast-derived cells. In addition, we showed that the hepatocyte growth factor activator, mitogen-activated protein kinase kinase 1, and phosphatidylinositol 3-kinase signaling pathways were involved in hepatic differentiation enhanced by HAI-2 knockdown. Conclusion: HAI-1 and -2 are overexpressed in the liver in cholangiopathies with ductular reactions and are possibly involved in liver fibrosis and hepatic differentiation; they could be investigated as disease markers and potential therapeutic targets. (HEPATOLOGY 2012;55:161-172)

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Extrahepatic biliary atresia: A first-trimester event? Clues from light microscopy and immunohistochemistry

Cited by 107 publications

References 18 publications

Nonvisualization of the fetal gallbladder by second‐trimester ultrasound scan: strategy of clinical management based on four examples

Nonvisualization of the fetal gallbladder by second‐trimester ultrasound scan: strategy of clinical management based on four examples

Cellular and humoral autoimmunity directed at bile duct epithelia in murine biliary atresia

Persistent elevation of hepatocyte growth factor activator inhibitors in cholangiopathies affects liver fibrosis and differentiation

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