Abstract:Aims/Background: The objective of this study was to characterize the expression of transforming growth factor-alpha/epidermal growth factor receptor, hepatocyte growth factor/c-met, transforming growth factor-beta/Type I-II transforming growth factor-beta receptors, stem cell factor, urokinase plasminogen activator, smooth muscle actin, CD34 and alpha-fetoprotein in human liver samples with (sub)massive necrosis of different etiology containing atypical ductular reaction. Methods: Their presence was studied by immunohistochemistry on paraffin-embedded tissue sections. Results: Transforming growth factor-alpha and -beta, hepatocyte growth factor and their receptors were demonstrated in the ductules; additionally stem cell factor and urokinase plasminogen activator were also expressed. The atypical ductules were surrounded by smooth muscle actin-positive activated stellate cells. Conclusion: These phenotypic similarities confirm that the atypical ductules in the human liver may be equivalent of oval cells in the rat liver, which are regarded as the progeny of stem cells. That is, the atypical ductular proliferation may correspond to a stem cell-fed regenerative process.