Quantitative morphometric and immunohistochemical analysis and their correlates in cirrhosis – A study on explant livers

Abstract

Background. Reproducible structural analysis was made on cirrhotic human liver samples in order to reveal potential connections between morphological and laboratory parameters. Material and methods. Large histological samples were taken from segment VII of 56 cirrhotic livers removed in connection with liver transplantation. Picro Sirius red and immunohistochemically (smooth muscle actin [SMA], cytokeratin 7 [CK7], Ki-67) stained sections were digitalized and morphometric evaluation was performed. Results. The Picro Sirius-stained fibrotic area correlated with the average thickness of the three broadest septa, extent of SMA positivity, alkaline phosphatase (ALP) values and it was lower in the viral hepatitis related cirrhoses than in samples with non-viral etiology. The extent of SMA staining increased with the CK7-positive ductular reaction. The proliferative activity of the hepatocytes correlated positively with the Ki-67 labeling of the ductular cells and inversely with the septum thickness. These data support the potential functional connection among different structural components, for example, myofibroblasts, ductular reaction and fibrogenesis but challenges the widely proposed role of ductular cells in regeneration. Conclusion.Unbiased morphological characterization of cirrhotic livers can provide valuable, clinically relevant information. Similar evaluation of routine core biopsies may increase the significance of this ‘Gold Standard’ examination.

Key Words:

• ductular reaction
• fibrosis
• hepatic myofibroblasts
• image analysis

Acknowledgements

Financial Support: Supported by Hungarian Scientific Research Fund (OTKA K100931 and PD109201). This research was supported by the European Union and the State of Hungary, co-financed by the European Social Fund in the framework of TÁMOP 4.2.4. A/1-11-1-2012-0001 ‘National Excellence Program’.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.