Theoretically, earlier cardiac transplantation may be beneficial, given that the hemodynamic improvement with additional cardiac surgeries Selleck AZD6244 is often limited. Furthermore, each additional surgery is associated with higher transfusion requirements with negative implications for future transplants and may increase the
complexity of cardiac transplantation. We anticipate that the hepatologist will play a central role in the multidisciplinary management of these complex patients. It is hoped that the formation of consortia may allow for better elucidation of the nature and frequency of complications as well as clarification of the optimal management in this vulnerable population. “
“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 DMXAA clinical trial 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 PKC inhibitor 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) Biliary atresia (BA) is one of the most important causes of hepatic fibrosis in children.1 Liver fibrosis is a complex process that involves extensive extracellular matrix (ECM) remodeling and proteolysis.2 Using microarray analysis, Chen et al.