Journal
JOURNAL OF PEDIATRIC SURGERY
Volume 36, Issue 7, Pages 1017-1025Publisher
W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1053/jpsu.2001.24730
Keywords
biliary atresia; cellular inflammation; portoenterostomy; macrophage; adhesion molecules
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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 semiquantative 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 in = 19]), and those who required liver transplantation or who had failed to clear their jaundice (defined as > 50 mu mol/L; graded as poor outcome [0 = 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 ton infiltrating cells) and ICAM ton endothelium) expressed strongly in the remnant bile duct tissue. Although quantitvely 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. Copyright <(c)> 2001 by W.B. Saunders Company.
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