New Alagille syndrome study findings have been reported from L. Fabris et al
2007 AUG 27 -- New research, "Analysis of liver repair mechanisms in Alagille syndrome and biliary atresia reveals a role for notch signaling," is the subject of a report. According to recent research from Bergamo, Italy, "Patients with Alagille syndrome (AGS), a genetic disorder of Notch signaling, suffer from severe ductopenia and cholestasis, but progression to biliary cirrhosis is rare. Instead, in biliary atresia (BA) severe cholestasis is associated with a pronounced "ductular reaction" and rapid progression to biliary cirrhosis." "Given the role of Notch in biliary development, we hypothesized that defective Notch signaling would influence the reparative mechanisms in cholestatic cholangiopathies. Thus we compared phenotype and relative abundance of the epithelial components of the hepatic reparative complex in AGS (n=10) and BA (n=30) using immunohistochemistry and computer-assisted morphometry. BA was characterized by an increase in reactive ductular and hepatic progenitor cells, whereas in AGS, a striking increase in intermediate hepatobiliary cells contrasted with the near absence of reactive ductular cells and hepatic progenitor cells. Hepatocellular mitoinhibition index (p21(waf1)/Ki67) was similar in AGS and BA. Fibrosis was more severe in BA, where portal septa thickness positively correlated with reactive ductular cells and hepatic progenitor cells. AGS hepatobiliary cells failed to express hepatic nuclear factor (HNF) 1beta, a biliary-specific transcription factor," wrote L. Fabris and colleagues, . The researchers concluded: "These data indicate that Notch signaling plays a role in liver repair mechanisms in postnatal life: its defect results in absent reactive ductular cells and accumulation of hepatobiliary cells lacking HNF1beta, thus being unable to switch to a biliary phenotype." Fabris and colleagues published their study in American Journal of Pathology (Analysis of liver repair mechanisms in Alagille syndrome and biliary atresia reveals a role for notch signaling. American Journal of Pathology, 2007;171(2):641-53). For additional information, contact L. Fabris, CeLiveR, Gastroenterology and Liver Transplant Unit, Ospedali Riuniti di Bergamo, Bergamo, Italy. Publisher contact information for the American Journal of Pathology is: American Society Investigative Pathology, Inc., 9650 Rockville Pike, Bethesda, MD 20814-3993, USA. Keywords: Italy, Bergamo, Alagille Syndrome, Biliary Atresia, Biliary Cirrhosis, Cholestasis, Cirrhosis, Fibrosis, Gastroenterology, Hepatology, Pathology. This article was prepared by Gastroenterology Week editors from staff and other reports. Copyright 2007, Gastroenterology Week via NewsRx.com.
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