Background: The authors studied the patterns of expression of immunologic costimulatory molecules (B7-1, B7-2, and CD40) in biliary atresia (BA) patients to confirm any correlation with clinical course/outcome.
Methods: Based on clinical status 2 years postoperatively, 24 BA patients were divided into group I (n = 8, normal liver function), group II (n = 10, anicteric with moderate liver dysfunction), and group III (n = 6, icteric with severe liver dysfunction). Liver biopsies obtained at portoenterostomy and from 6 age-matched controls, were analyzed immunohistochemically using antibodies against B7-1, B7-2, and CD40.
Results: There was no expression of B7-1, B7-2, or CD40 in any control liver specimen. In all BA specimens, B7-1, B7-2, and CD40 were expressed strongly in bile ductules in portal tracts. In groups with liver dysfunction, B7-1, B7-2, and CD40 were expressed strongly on the surfaces of Kupffer and dendritic cells and in hepatocyte cytoplasm. Positive staining cells were significantly fewer in patients with better clinical outcome. B7-1 was found in vascular and sinusoidal endothelial cells only in cases of postoperative portal hypertension.
Conclusions: Costimulatory factors expressed on bile ductules, hepatocytes, and vascular endothelial cells appear to mediate autoimmune processes causing progressive liver fibrosis and portal hypertension in BA.