Indirect immunohistochemical evaluation of graft fibrosis and interface hepatitis after pediatric liver transplantation.

ABSTRACT

Fibrosis or IH following pediatric liver transplantation is recognized as major causes of graft loss, but the etiology remains unclear. To determine this issue, we used an indirect immunohistochemistry technique with post-transplant serum samples from recipients and normal human liver tissues from living liver donors, and the association between occult antibody reaction to the liver and the occurrence of fibrosis or IH was evaluated. Forty-three recipients were evaluated, and both hepatocytes and biliary epithelial cells were evaluated for staining intensity. Fibrosis and IH occurred in 13 and six patients, respectively. According to staining results for the hepatocytes and biliary epithelial cells, 18 and 11 patients, respectively, were classified into the positive group. According to log-rank analysis, positive reaction for hepatocytes was associated with increased rates of fibrosis and IH (p = 0.002 and 0.048, respectively), while positive reaction for biliary epithelial cells was associated with an increased rate of fibrosis (p = 0.014). Multivariate analysis revealed that positive reaction for hepatocytes and biliary epithelial cells was independently associated with fibrosis occurrence (p = 0.020 and 0.047, respectively). In conclusion, immune-mediated reactions by occult antibodies may underlie the pathogeneses of fibrosis and IH.