Size of portally deprived liver lobe after portal vein ligation and additional partial hepatectomy: Result of balancing proliferation and apoptosis

Abstract

The liver has the ability to maintain its total size by adjusting the size of the individual liver lobes differently in response to regeneration-and atrophy-stimuli. Portal vein ligation (PVL) drives the ligated lobe to undergo atrophy whereas partial hepatectomy (PHx) drives the total remnant liver to regenerate. We hypothesize that the size of the PVL-lobe is dependent on the balance between the extent of PVL and the extent of PHx inducing a complex interplay between hepatocyte proliferation, apoptosis and autophagy. Lewis-rats were subjected to either 20%PVL + 70%PHx or 70%PVL + 20%PHx. Control groups consisted of 20%PVL and 70%PVL. Liver lobe weight, BrdUproliferation-index, proliferating-cell-nuclear-antigen-mRNA-expression level, apoptotic density and autophagy-related-proteins were investigated. The PVL-liver lobe adjusted its weight differently, increasing by 40% after 20%PVL + 70%PHx, but decreasing by 25% after 70%PVL + 20%PHx. Additional resection induced a low, but substantial size-dependent hepatocyte proliferation rate (maximal 6.3% and 3.6% vs. 0.3% and significantly suppressed apoptotic density in the deportalizedliver-lobe (3 and 14 cells/mm 2 comparing with above 26 cells/mm 2 , p < 0.01). Autophagy was more activated in PVL-liver lobe after simultaneous PHx than after PVL only. In summary, atrophy of the PVLliver lobe after simultaneous PHx was counteracted by promoting hepatocyte proliferation, inducing autophagy and suppressing apoptosis in a PHx-extent-dependent manner.

Additional partial hepatectomy at the time of portal vein ligation accelerates the regeneration of the future liver remnant

“…However, performing a small additional resection (20%PHx) did not fully prevent atrophy of the ligated liver lobe, but reduced the extent of atrophy substantially compared to PVL alone. Furthermore, we observed an induction of proliferation, down-regulation of apoptosis and an up-regulation of autophagy in the ligated lobe 18 . In other words, the additional resection had a substantial impact on the size regulation of the ligated lobe, which was related to the extent of the additional resection.…”

“…In our previous studies 17,18 , we established a rat model combined PVL and PHx. We investigated the influence of additional PHx on the ligated liver lobe.…”

A Prospective Study of Liver Regeneration After Radiotherapy Based on a New (Su’S) Target Area Delineation

“…Inadequate functional liver volume is also a major cause of liver function deterioration after radiotherapy. Therefore, compensating for the loss of liver mass by regeneration is of great importance, especially in patients with large tumors and limited healthy livers ( 28 ). Consequently, a precise radiotherapy plan based on the accurate prediction of liver regeneration is urgently needed in clinical practice.…”

Hepatectomy-Induced Alterations in Hepatic Perfusion and Function - Toward Multi-Scale Computational Modeling for a Better Prediction of Post-hepatectomy Liver Function

“…The impact of obstructive jaundice on liver regeneration was studied by first performing bile duct ligation 1 week prior to liver resection (Li 2014). Different models of 2-stage hepatectomy (e.g., 70% PVL with (ALPPS) or without transection of the median lobe followed by PHx of atrophied liver lobes) were developed to better assess the impact of preventing collateral formation (García-Pérez et al, 2015;Wei et al, 2020). Here actually, the development of animal model only happened after introducing the procedure into clinic (Schnitzbauer et al, 2012).…”

“…A similar effect on regeneration of the FLR was observed when inducing congestion of the portally ligated lobe by performing an additional ligation of the left lateral hepatic vein along with PVL. Combination of an additional resection with PVL induced hepatocyte proliferation in the portally deprived liver lobe (Wei et al, 2020 ). In conclusion, the wide spectrum of surgical models, which emerged over the years, is very useful to investigate the different facets of liver regeneration and the underlying complex pathophysiological mechanism (see Table 2 ).…”