Published online Mar 14, 2018. doi: 10.3748/wjg.v24.i10.1107
Peer-review started: December 29, 2017
First decision: January 17, 2018
Revised: February 4, 2018
Accepted: February 9, 2018
Article in press: February 9, 2018
Published online: March 14, 2018
Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has been increasingly popular worldwide recently. However, the high mortality makes surgeons reconsider the difference between functional and volumetric proliferation in ALPPS-derived liver regeneration. In this study, we therefore establish a rat model to mimic the ALPPS, exploring whether the functional proliferation lags behind the hypertrophy in volume.
This was a preliminary study with regard to the maturity of ALPPS-derived liver regeneration. On the basis of developing a rat model, we found the volumetric assessment overestimated the functional proliferation in ALPPS procedure, which indicated the stage II of ALPPS should be performed prudently in patients with marginally adequate future liver remnant.
This study was to evaluate the maturity of ALPPS-derived liver regeneration. In our rat model, the postponed maturity in function might be an important reason for high mortality of ALPPS even when the adequate future liver remnant was achieved before stage II of ALPPS. Likewise, the functional proliferation should be performed to time the stage II of ALPPS clinically.
In this study, ALPPS, partial hepatectomy (PHx) and sham models were conducted. The ratio of right middle lobe to body weight as well as proliferative markers were used for assessing the liver regeneration. Morphological changes by HE stain and detection of specific markers of progenitor or mature hepatocytes were adopted to identify the characteristics of newborn hepatocytes. Eventually, the liver function in vivo and vitro was measured, followed by the cluster analysis of expression of functional genes to detect the maturity of liver regeneration from different models.
By establishment of ALPPS, PHx and sham models, we demonstrated that ALPPS could induce an accelerated proliferative response. However, the characteristics of newborn hepatocytes seemed to be not mature completely. Sox9 positive hepatocyte, as well as different expression of other specific markers, indicated the potential role of progenitor hepatic cell in ALPPS-derived regeneration. Parts of limited liver function and different expression of functional genes supported the above-mentioned immaturity in ALPPS-induced proliferation.
As the mortality remains unsatisfactory even in patients with adequate future liver remnant after stage I of ALPPS, this study presented the immaturity of ALPPS-derived proliferation in early regenerative response, which indicated that the volumetric assessment overestimated the functional proliferation. To the best of our knowledge, this is the first study to evaluate the maturity of ALPPS-derived liver regeneration in a rat model. Meanwhile, Sox9 positive hepatocyte indicated the potential role of hepatic progenitor cell in the ALPPS rather than conventional PHx model. Therefore, a more detailed research about the hepatic progenitor cell promotes the ALPPS-derived liver regeneration and its mechanism would be done in our next work.
The stage II of ALPPS should be performed prudently in patients with marginally adequate future liver remnant, as the ALPPS-derived proliferation in volume lags behind the functional regeneration. By the way, as the hepatic progenitor cell might be an important role in ALPPS-derived liver regeneration, our future work is to further demonstrate the fate of Sox9 positive hepatocyte with ALPPS procedure and its underlying mechanism by lineage tracing method.