Liver regeneration: mechanisms and markers

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].