Liver regeneration after hepatectomy.

Following hepatectomy, liver "knows" when to start and when to stop growing, and thereby accurately regulates its mass. Partial hepatectomy triggers hepatocyte proliferation whereas excessive liver mass (transplant) is regulated by apoptosis. Liver regeneration mainly involves the activation of adult hepatocytes and possibly of liver precursor ("stem") cells. The multistep process of liver regeneration comprises at least 2 critical phases: the transition of the quiescent hepatocyte into the cell cycle (priming) and the progression beyond the restriction point in the G1 phase of the cycle. The priming phase is characterized by the expression of immediate early genes. Activation of protooncogenes in the immediate early gene response involves both transcriptional and post-transcriptional mechanisms. Activation of four transcription factors, NF kappa B, STAT3, AP-1, and C/EBP beta, causes secondary activation of multiple genes and plays an important role in the initiation of hepatic regeneration. The passage of primed hepatocytes through the cell cycle is characterized by the expression of cell cycle genes and requires growth factors. An equilibrium between stimulator and inhibitor genes of the cell cycle expressed after hepatectomy, may explain why the liver regeneration is a tightly regulated growth process. Based on the knowledge of the regulation of liver regeneration, several practical considerations and potential therapeutic strategies can be applied in humans with hepatic dysfunction due to liver resection.