Immunohistochemical classification of ductular reactions in human liver

Aims: Ductular reactions occur in a wide variety of liver diseases. Their origin and function is still debated. Our understanding of these histological reactions is impaired by their great diversity; therefore rational classification should precede further detailed analysis. The aim was to achieve a reproducible classification of hepatic ductular reactions based on their immunophenotype. Methods and results: Sixty-nine liver specimens with ductular reactions were analysed by immunohistochemistry. The majority of the samples could be classified into three categories based on their immunophenotype. Type P(rimitive) reaction is characterized by CD56 immunoreactivity. Most primary biliary cirrhosis and focal nodular hyperplasia samples fall into this group; these ductules do not show any sign of differentiation. Type D(ifferentiating) ductules are positive for CD56, epithelial membrane antigen (EMA) and CD10. Cirrhotic samples and regenerating livers following fulminant hepatic failure contain such ductular reactions; this immunophenotype indicates hepatocytic differentiation. Biliary obstruction results in EMA-positive type O(bstructive) reactions; these ductules are similar to the normal interlobular bile ducts. Conclusion: Ductular reactions can be classified based on their immunophenotype. Our results may initiate further, similar, studies resulting in a generally accepted rational classification. We believe that such categorization is necessary for elucidating their biological and clinical significance.