Immunohistochemistry of the liver and biliary tree in extrahepatic biliary atresia.

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. 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]). 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. 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.

Davenport M ，Gonde C ，Redkar R ，Koukoulis G ，Tredger M ，Mieli-Vergani G ，Portmann B ，Howard ER ... -  《JOURNAL OF PEDIATRIC SURGERY》

Immune-mediated liver injury: prognostic value of CD4+, CD8+, and CD68+ in infants with extrahepatic biliary atresia.

Kotb MA ，El Henawy A ，Talaat S ，Aziz M ，El Tagy GH ，El Barbary MM ，Mostafa W ... -  《-》

Immunohistochemical analysis of adhesion molecules in the micro-environment of portal tracts in relation to aberrant expression of PDC-E2 and HLA-DR on the bile ducts in primary biliary cirrhosis.

Yasoshima M ，Nakanuma Y ，Tsuneyama K ，Van de Water J ，Gershwin ME ... -  《JOURNAL OF PATHOLOGY》

Increased expression of intercellular adhesion molecules in biliary atresia.

Dillon P ，Belchis D ，Tracy T ，Cilley R ，Hafer L ，Krummel T ... -  《-》

Implication of adhesion molecules in inflammation of the common bile duct in patients with secondary cholangitis due to biliary obstruction.

Gulubova M ，Vlaykova T ，Manolova I ，Hadjipetkov P ，Popharitov A ... -  《hepato-gastroenterology》