Positive C4d staining of the portal vein endothelium in the liver of patients with biliary atresia: a role of humoral immunity in ongoing liver fibrosis

• Published in: Pediatric surgery international 2014-09, Vol.30 (9), p.877-881
• Main Authors: Fujisawa, Sorahiko, Muraji, Toshihiro, Sakamoto, Naoya, Hosaka, Naoki, Matsuda, Satoshi, Kawakami, Hajime, Hirai, Misako, Yanai, Toshihiro
• Format: Article
• Language: English
• Subjects: Age Factors; Biliary Atresia - complications; Biliary Atresia - immunology; Biliary Atresia - pathology; Biopsy; Complement C4b - immunology; Endothelium - pathology; Endothelium - ultrastructure; Female; Fluorescent Antibody Technique - methods; Follow-Up Studies; Humans; Immunity, Humoral - immunology; Infant; Liver - immunology; Liver - pathology; Liver Cirrhosis - complications; Liver Cirrhosis - immunology; Liver Cirrhosis - pathology; Male; Medicine; Medicine & Public Health; Observer Variation; Original Article; Pediatric Surgery; Pediatrics; Peptide Fragments - immunology; Portal Vein - immunology; Portal Vein - pathology; Portal Vein - ultrastructure; Severity of Illness Index; Surgery
• ISSN: 0179-0358; 1437-9813
• DOI: 10.1007/s00383-014-3553-3

Purpose This study aimed to clarify the role of complement activation in fibrogenesis in BA. Methods In total, 27 paraffin-embedded liver biopsy samples were immunohistochemically analyzed using C4d polyclonal antibody, vascular cell adhesion molecule-1 (VCAM-1), and CD45. The liver samples were obtained from 25 patients during Kasai operation, and two additional specimens were obtained from 2 patients by needle biopsy later at the time of liver function deterioration. The degree of liver fibrosis was histologically graded 1–3. Results Among the 25 samples, 9 showed C4d-positive immunostaining localized on the endothelia of a few portal veins in the portal tract. The degree of fibrosis was correlated with C4d staining ( p  = 0.025). The age at Kasai operation correlated with the degree of fibrosis and the C4d positivity. Two needle biopsy samples were positive for C4d. Among 13 samples submitted for VCAM-1 staining, 2 negative samples were C4d negative and all positive C4d samples were VCAM-1 positive with CD45 mononuclear cell infiltration. Conclusion These findings suggest that ongoing cirrhosis could be a result of progressive “vasculopathy” of the portal vein caused by humoral and cell-mediated immune interaction.