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22 - Liver regeneration: mechanisms and markers
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- By Nelson Fausto, Jean Campbell, University of Washington School of Medicine, Seattle, Washington, USA
- Edited by Andrew K. Trull, Lawrence M. Demers, David W. Holt, Atholl Johnston, J. Michael Tredger, Christopher P. Price
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- Book:
- Biomarkers of Disease
- Published online:
- 20 August 2009
- Print publication:
- 06 June 2002, pp 239-243
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Summary
Introduction
During liver regeneration, quiescent differentiated hepatocytes replicate to restore hepatic tissue. Regeneration can be triggered by the surgical removal of liver tissue or by hepatocyte loss caused by chemical or viral injury. Regardless of the cause, hepatocytes proliferate in a relatively synchronous way to restore the functional capacity of the liver. The most extensively studied model of liver regeneration is that which occurs after removal of two-thirds of the liver (partial hepatectomy). Remarkably, this process, which is referred to as ‘regeneration’, does not involve true regenerative growth [1]; the hepatic lobes removed by the operation do not grow back. Instead, hepatic mass increases by compensatory hyperplasia of the remaining lobes. These lobes increase in size as a consequence of hepatocyte proliferation and the process terminates when the mass of the enlarged lobes reaches that of the original liver. This chapter will highlight the precise regulatory controls which are activated during this remarkable growth process and identify those key components that may be considered as candidate biomarkers of regeneration. In rodents, 90–95% of hepatocytes replicate within 2 days after partial hepatectomy. DNA replication is preceded by a prereplicative phase in which a large number of genes are activated [2].
Experimental and clinical features
Liver regeneration is important both from a scientific perspective and clinically. The same growth factors that regulate liver regeneration in rodents also appear to be active in humans.
9 - Hepatocyte replication and liver regeneration
- from Part Two - Mechanisms of Disease and Multisystem Involvement
- Edited by William M. Lee, University of Texas Southwestern Medical Center, Dallas, Roger Williams, University College London
- Foreword by Jean-Pierre Benhamou, Jacques Bernuau
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- Book:
- Acute Liver Failure
- Published online:
- 20 May 2010
- Print publication:
- 28 December 1996, pp 93-114
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Summary
INTRODUCTION
Hepatocytes are highly differentiated cells which have little proliferative activity in adult livers of humans or animals. Nevertheless, the proliferative capacity of hepatocytes is not lost and is rapidly activated in response to decreases in functional hepatic mass caused by tissue resection or cell death (Bucher and Malt 1971; Fausto and Webber 1994). During the last few years much new information has become available on the role of transcription factors, proto-oncogenes and growth factors as mediators of the process by which quiescent hepatocytes enter the cell cycle and replicate. Most of this knowledge has been obtained from studies of liver regeneration after partial hepatectomy (PH) in rodents and from work with cultured hepatocytes. In liver regeneration induced by partial hepatectomy, hepatocyte replication occurs in the absence of concomitant cell death and fibrogenesis. Thus, the system is most suitable for the analysis of the molecular mechanisms of hepatocyte replication and growth factor effects. More over the results of these studies are applicable to the understanding of growth regulation in human livers. However, hepatocyte replication in humans often takes place in diseased livers in which the tissue architecture is grossly altered, or, in the case of acute hepatic failure, in an organ with massive cell death and impaired function.
It is not known whether the molecular mechanisms of hepatic replication after partial hepatectomy of a normal organ differ from those which regulate hepatocyte proliferation after severe injury.