Abstract
The liver is a unique organ with an abundant regenerative capacity. Therefore, partial hepatectomy (PHx) or partial liver transplantation (PLTx) can be safely performed. Liver regeneration involves a complex network of numerous hepatotropic factors, cytokines, pathways, and transcriptional factors. Compared with liver regeneration after a viral- or drug-induced liver injury, that of post-PHx or -PLTx has several distinct features, such as hemodynamic changes in portal venous flow or pressure, tissue ischemia/hypoxia, and hemostasis/platelet activation. Although some of these changes also occur during liver regeneration after a viral- or drug-induced liver injury, they are more abrupt and drastic following PHx or PLTx, and can thus be the main trigger and driving force of liver regeneration. In this review, we first provide an overview of the molecular biology of liver regeneration post-PHx and -PLTx. Subsequently, we summarize some clinical conditions that negatively, or sometimes positively, interfere with liver regeneration after PHx or PLTx, such as marginal livers including aged or fatty liver and the influence of immunosuppression.
Highlights
As presented in the myth of Prometheus in ancient Greek mythology, the liver is an organ in the human body with a rapid and abundant regenerative capacity
Using genetic fate mapping and a high-throughput imaging system of individual hepatocytes, Miyaoka et al reported that the volume of hepatectomy affected the mode of liver regeneration; i.e., while the remnant liver following 30% partial hepatectomy (PHx) regenerated solely by hypertrophy without cell division, hypertrophy and subsequent proliferation almost contributed to regeneration after 70% PHx [4]
Campbell et al showed that knockout mice of myeloid differentiation factor 88, a common adaptor molecule required for signaling mediated by Toll-like receptors (TLRs), showed severely decreased liver Tnf mRNA expression and circulating IL-6 levels after PHx compared with wild-type mice [29]. These results suggest that LPS and TLRs are not the only factors affecting Kupffer cells and that various factors and receptors may trigger the release of IL-6 or tumor necrosis factor (TNF)-α from Kupffer cells
Summary
As presented in the myth of Prometheus in ancient Greek mythology, the liver is an organ in the human body with a rapid and abundant regenerative capacity. The regeneration rate is higher in the recipient’s left lobe graft than in the donor’s remaining left lobe [3] They showed that the recipient liver volume increased rapidly in the first 2 months, exceeding the standard liver volume, and gradually decreased to 90% of the standard liver volume [3]. Most hepatocytes entered the cell cycle after 70% PHx, only about half of the hepatocytes underwent cell division during liver regeneration, leading to an increase in hepatocyte ploidy [4] These results suggest that liver regeneration is a flexible and variable process that depends on the condition of the remaining liver, graft, and metabolic environment of the host
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