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Background/purpose: Despite improvements in the surgical management of biliary atresia, the long-term incidence of progressive liver failure remains high. Because chronic inflammation involving both bile ducts and liver parenchyma contributes to the pathology, the authors have hypothesized that the liver damage may be altered using immunosuppressive therapy. The aim of this study was to examine the safety and efficacy of long-term steroid therapy in patients with biliary atresia., Methods: A retrospective analysis of all patients with biliary atresia treated with an hepatoportoenterostomy and postoperative steroid therapy at our 3 institutions was undertaken. Patients were treated uniformly with immunosuppressive doses of oral steroids for a minimum of 6 weeks after surgery., Results: Twenty-five infants with biliary atresia were treated with steroid therapy. Overall survival rate was 22 patients (88%) with a mean follow-up period of 50 months. Nineteen patients (76%) became jaundice free with native liver function. Four patients (16%) did not respond to treatment and required transplantation. Age less than 12 weeks was a crucial predictor of success of adjuvant steroid therapy. Cholangitis developed in 8 patients (32%). There were no complications caused by steroid therapy., Conclusions: Steroid administration at immunosuppressive doses markedly improves the clinical outcome within the first 5 years after surgery as measured by jaundice-free status and survival without liver transplantation when compared with concurrent reports. These results suggest that immunosuppressive therapy is safe and has a positive impact on the clinical course of this disease. However, a randomized study is needed to ultimately prove such an hypothesis.

The expression of the inflammatory adhesion molecules intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and endothelial leukocyte adhesion molecule-1, was studied in six infants with biliary atresia using an immunoperoxidase technique on frozen sections. Controls consisted of five patients with various conditions including total parenteral nutrition-induced cholestasis, choledochal cyst, viral hepatitis, metastatic carcinoma, and thrombotic thrombocytopenic purpura. None of the patients were in liver failure. Bile ducts from the control subjects did not express any of the inflammatory adhesion molecules on ductal epithelium. In marked contrast, all of the biliary atresia specimens demonstrated strong intercellular adhesion molecule-1 expression and occasional vascular cell adhesion molecule-1 staining on epithelial cell membranes of both intra- and extrahepatic ductal structures. Hepatocytes and sinusoidal lining cells including Kupffer cells showed a pattern of intense intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression in all specimens with active inflammation that could not differentiate the biliary atresia cases from the control group. Lymphocyte function-associated antigen-1 intensely stained the inflammatory cell infiltrate in the biliary atresia and inflamed control specimens. The strong expression of intercellular adhesion molecule-1 on biliary ductal epithelium in patients with biliary atresia suggests a potential role for this adhesion molecule in the pathogenesis of this devastating neonatal hepatic disorder.