Abnormalities of Liver Regeneration: A Review

Abstract

Structural and functional changes during liver regeneration have been studied extensively in experimental animals following partial hepatectomy or hepatic injury induced by noxious substances. These observations have been extended to evaluate abnormalities of liver regeneration which contribute to chronic hepatitis, cirrhosis and/or liver cancer in man. This is facilitated by the simultaneous perfusion of flash frozen percutaneous biopsies or explanted liver in an acrylic chamber with tritiated thymidine and proline to evaluate DNA and collagen synthesis, respectively. Such investigations indicate that chronic liver damage is associated with replication of mesenchymal, ductular and parenchymal cells, accompanied by increased fibrogenesis. The regenerative response of the liver after noxious injury in experimental animals and man is associated with the release of cytokines, increase of growth response genes and change in telomerase activity. The ability to monitor morphological, genetic and biochemical parameters provides new information on the kinetics of the reparative process in hepatobiliary disease. Abnormal liver regeneration and its untoward effects including tumorigenesis may be modified by altering nutrients, blocking antigens or receptors, and inhibiting metabolites which regulate cell replication and collagen deposition.

βA- and βC-activin, follistatin, activin receptor mRNA and βC-activin peptide expression during rat liver regeneration

“…Examining the expression of genes shown to be associated with activin-mediated cell cycle arrest in vitro in an in vivo model of liver regrowth may provide further evidence as to the mechanisms by which activins control hepatocyte cell growth. Follistatin has previously been shown to increase DNA synthesis and to antagonise the inhibitory effects of activin A in regenerating liver (Kogure et al 1995, 1998, 2000, Zhang et al 1997a. The increase in follistatin demonstrated in our study may therefore serve to protect proliferating hepatocytes from the apoptotic effects of activin A. Mitosis was evident at 48-72 h when follistatin mRNA expression was high.…”

“…In the normal liver the expression of activin A is relatively low (Yasuda et al 1993). Activin A is involved in the maintenance of constant liver mass, since blocking activin A action by administering the activin-binding protein follistatin leads to hepatocyte proliferation (Kogure et al 1995, 1998, 2000, Kozian et al 1997, Zhang et al 1997a). Activin A is also up-regulated in the development of liver cirrhosis concomitant with an increase in hepatocyte apoptosis (Gold et al 2003).…”

“…Thus C-activin has been shown to be either growth inhibitory (Esquela et al 1997, Zhang et al 1997b or growth promoting (Kobayashi et al 2002, Wada et al 2004 in liver. A balance between cell proliferation and apoptosis is crucial for regulating normal liver function (Chen et al 2000), since abnormalities in liver regeneration may contribute to chronic hepatitis, cirrhosis and cancer (Leevy 1998). Cellular control of activin expression appears to occur at many levels, including the amount of growth factor, dimer combinations formed, the presence of binding proteins, receptor recruitment and presence of other peptides (Phillips 2000).…”

The mystery of liver regeneration

“…Restoration of normal liver architecture usually occurs after removal of the injurious factors causing liver damage. However, in the presence of continued injury, replication of hepatocytes, ®brosis, vascular abnormalities, and cirrhosis and/or cancer may ensue 20 . There is evidence to suggest that the mechanisms of regeneration may vary depending on the type of insult that the liver sustains.…”

Liver regeneration in donors and adult recipients after living donor liver transplantation

“…Precise evaluations of donor liver volume are important in order to prevent unexpected hepatic insufficiency and to evaluate normal liver regeneration, which is still unknown to a great extent. Several authors have studied liver regeneration, mostly in diseased livers 8, 9. Complete and prompt liver regeneration occurs in donors and recipients in most circumstances 10, 11.…”