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  • Title: Immunohistochemistry of the liver and biliary tree in extrahepatic biliary atresia.
    Author: Davenport M, Gonde C, Redkar R, Koukoulis G, Tredger M, Mieli-Vergani G, Portmann B, Howard ER.
    Journal: J Pediatr Surg; 2001 Jul; 36(7):1017-25. PubMed ID: 11431768.
    Abstract:
    BACKGROUND: Progressive destruction of intrahepatic bile ducts may determine outcome in extrahepatic biliary atresia (EHBA) despite successful portoenterostomy. The aim of this study was to characterize the inflammatory infiltrate of a large series of cases of biliary atresia and relate these findings to clinical outcome. METHODS: Immunohistochemical analysis was performed on frozen tissue sections of extrahepatic biliary tree and liver biopsies obtained (August 1996 to March 1998) from 28 infants with EHBA and 8 liver biopsy specimens from age-matched controls with other cholestatic liver disorders. A semiquantitative scoring system was designed to evaluate the staining with a panel of antibodies to the CD4, CD8, CD25, CD56, CD68, CD71 antigens and to HLA-DR, ICAM-1, VCAM-1, E-selectin and LFA-1. The infants then underwent followup prospectively and divided into 2 prognostic groups at 12 months postoperatively: those who had cleared their jaundice (graded as a good outcome [n = 19]), and those who required liver transplantation or who had failed to clear their jaundice (defined as > 50 micromol/L; graded as poor outcome [n = 9]). RESULTS: CD4(+) lymphocytes and CD56(+) (NK cells) predominated in the liver of infants with EHBA as compared with controls. The infiltrating cells exhibited marked proliferation (CD71 expression) and activation (particularly LFA-1 but also CD25 expression). A smaller subpopulation of the cells also expressed VCAM and E-selectin. HLA-DR was strongly expressed on Kupffer cells and to a lesser extent on proliferating bile ducts and sinusoidal endothelium. Expression of the majority of markers was lower in the remnant bile duct tissue than in the liver of EHBA (P <.05) with only HLA-DR and LFA-1 (on infiltrating cells) and ICAM (on endothelium) expressed strongly in the remnant bile duct tissue. Although quantitatively less pronounced, all of these immunohistochemical features also were noted in non-EHBA cholestatic liver tissue. A good outcome at 12 months was associated with lower CD68 (macrophage) expression in both the liver (P <.05) and biliary tree (P <.05) and with reduced expression of ICAM-1 (P =.05) on infiltrating cells in the biliary remnant. CONCLUSIONS: Immunohistochemical patterns of immune-mediated liver injury and inflammation were prevalent features at the time of portoenterostomy. They were neither exclusive to nor characteristic of EHBA. A reduction in the expression of the macrophage marker (CD68) within the liver and biliary remnants and reduction of ICAM-1 expression on infiltrating cells in the biliary remnants appear to be associated with a better postoperative prognosis.
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