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

Pediatr Surg Int. 2014 Sep;30(9):877-81. doi: 10.1007/s00383-014-3553-3. Epub 2014 Jul 27.


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.

MeSH terms

  • 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
  • Observer Variation
  • Peptide Fragments / immunology*
  • Portal Vein / immunology*
  • Portal Vein / pathology
  • Portal Vein / ultrastructure
  • Severity of Illness Index


  • Peptide Fragments
  • Complement C4b
  • complement C4d