| Surgical resection is recommended for patients with resectable hepatocellular carcinoma.The future liver remnant(FLR)should be large enough to avoid post-hepatectomy liver failure(PHLF),which can also be prevented by associating liver partition and portal vein ligation for staged hepatectomy(ALPPS).Recent studies showed that hepatocyte nuclear factor 4 alpha(HNF4 α)was essential for the maintenance of liver specific function and for the prevention of mortality after partial hepatectomy(PHx)in mice.purpose:We investigate the mechanism how ALPPS prevents PHLF,especially the role of HNF4α and the atrophic liver tissue.Herein,we hypothesis that HNF4α in FLR improves the liver function and prognosis in ALPPS,which may be further indirectly stabilized by the atrophic liver tissue.Methods:Firstly,we establish the 80%ALPPS rat model and the corresponding 80%PHx model(also named extended hepatectomy,ePHx),and 70%ALPPS and 70%PHx model as control groups.Secondly,we compared the prognosis(including survival rate,liver function,rate of liver regeneration and morphology characteristic),liver regeneration(including the expression of Ki-67,EDU staining and activity of signaling related to liver regeneration),and liver specific function in FLR(glycogen storage,expression of albumin,and expression of genes related to liver specific function).Thirdly,we verified the protein expression of HNF4α and its transcriptional activity.Last but not least,we analyzed the viability and liver function of the atrophic liver tissue,and destroyed the atrophic liver tissue via hepatic pedicle ligation,to investigate its contribution to the expression of HNF4α in FLR and the prognosis.Results:Results showed that 80% ALPPS prevented PHLF and mortality in rats.Compared to 80%ALPPS,the regenerative response of 80%PHx was increased during 24-48 h post-surgery with significant impairment of liver specific function,and the HNF4αprotein expression and transcriptional activity were dramatically decreased at the early stage.Further study showed that the atrophic liver tissue maintained modest liver specific function after ALPPS;hepatic pedicle ligation resulted in avascular necrosis and loss of function;and the functional atrophic liver tissue stabilized the expression of HNF4 a in FLR and improved the prognosis after ePHx.Conclusion:In conclusion,we tend to attribute PHLF to the severe impairment of HNF4α-mediated liver specific function,rather than the repression of hepatocyte proliferation,and we find that the functional atrophic liver tissue is an efficient method to stabilize HNF4 a and improve the prognosis after ePHx. |
