*‘Clinical Fundamental Researchers’ of the ‘Fonds voor Wetenschappelijk Onderzoek’ Vlaanderen.
Liver regeneration in acute severe liver impairment: a clinicopathological correlation study
Article first published online: 8 NOV 2006
Volume 26, Issue 10, pages 1225–1233, December 2006
How to Cite
Katoonizadeh, A., Nevens, F., Verslype, C., Pirenne, J. and Roskams, T. (2006), Liver regeneration in acute severe liver impairment: a clinicopathological correlation study. Liver International, 26: 1225–1233. doi: 10.1111/j.1478-3231.2006.01377.x
- Issue published online: 8 NOV 2006
- Article first published online: 8 NOV 2006
- Received 21 May 2006,accepted 5 September 2006
- acute liver failure;
- hepatic progenitor cells (HPCs);
- hepatocyte loss;
- hepatocyte proliferation;
- intermediate hepatocytes;
- model for end stage liver diseases (MELD)
Abstract: Background: Although normally quiescent, the adult mammalian liver possesses a great capacity to regenerate after different types of injury. Major players in the regeneration process are mature residual cells, including hepatocytes, cholangiocytes and stromal cells. However, if the regenerative capacity of mature cells is impaired, hepatic progenitor cells (HPCs) are activated and expand into the liver parenchyma. Upon transit amplification, the progenitor cells generate new hepatocytes and biliary cells to restore liver homeostasis.
Aims/Methods: To study the relationship between different histopathological parameters as well as their correlations with clinical parameters and outcome, we examined liver specimens from 74 patients with acute or subacute severe liver impairment by immunohistochemistry for CK7/CK19 (evaluation of HPCs activation/differentiation), Mib1(Ki 67)/P21 (evaluation of proliferative activity/proliferation arrest of hepatocytes) and hematoxylin and eosin (evaluation of hepatocyte loss).
Results: Of the 74 patients, 32% survived without transplantation, 14% died without transplantation and 54% were transplanted. Our results show that a threshold of 50% loss of hepatocytes, associated with significant decrease in the proliferative activity of remaining mature hepatocytes, is needed for extensive hepatic progenitor cell activation. Such activation is a sign of disease severity and occurs early (within 1 week) in the disease course. However, development of intermediate hepatocytes, suggesting HPCs differentiation towards mature hepatocytes, takes at least 1 week's time. We found a positive correlation between histopathological parameters (percentage hepatocyte loss, number of proliferating hepatocytes and number of HPCs) and clinical parameters of liver impairment such as model for end stage liver diseases (MELD). Surviving patients compared with those who either died or were transplanted had significantly less hepatocyte loss, less HPCs activation and more mature hepatocyte proliferative activity. Hepatocyte proliferative activity and degree of hepatocyte loss were the most important independent histopathological parameters in predicting outcome.
Conclusion: Liver biopsy can provide important additional information in a patient with severe acute liver impairment.