The associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) procedure promotes the proliferation of the future liver remnant, but evidence to support the feasibility of ALPPS in livers with fibrosis is needed. Therefore the aim of this study was to establish a fibrotic ALPPS model in the rat to compare the capacity of regeneration in the remnant liver with or without fibrosis.
In our study we first established a thioacetamide-induced fibrotic ALPPS model in rats. Then the ALPPS-induced regenerative capacities of normal and fibrotic liver were compared in this animal model. In addition, markers of regeneration, including the proliferative index and cyclin D1 and proliferating cell nuclear antigen levels, as well as various indicators of liver function were determined to evaluate the quality of the hepatic regeneration.
Compared with that of the sham group (opening of the peritoneal cavity with no further operative manipulation), the proliferation of the future liver remnant in fibrotic rat liver after the ALPPS procedure was increased on postoperative days 1, 2, and 5 (P < .039 each). In addition, the proliferative response was greater in the ALPPS group than in the ligation group subjected only to portal vein ligation of the left lateral, left middle, right, and caudate lobes (P = .099, P = .006, and P = .020 on postoperative days 1, 2, and 5, respectively). In contrast, the ALPPS-induced regenerative capacity in the fibrotic rat livers was attenuated compared with that in the normal liver on postoperative days 1, 2, and 5 (P < .031 for each) after stage I and on postoperative day 5 after stage II of the ALPPS procedure (P < .005). This attenuated the recovery of liver function, and the greater mortality rate indicated that functional proliferation was either delayed or not as extensive in the fibrotic rat livers.
Through establishing a rat model of thioacetamide-induced liver fibrosis, we found that ALPPS-derived liver regeneration was present and feasible in fibrotic livers, but this effect was attenuated compared with that in normal liver.
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to Surgery
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- Impact of viral status on survival in patients receiving sorafenib for advanced hepatocellular cancer: a meta-analysis of randomized phase III trials.J Clin Oncol. 2017; 35: 622-628
- Estimating the world cancer burden: Globocan 2000.Int J Cancer. 2001; 94: 153-156
- Right portal vein ligation combined with in situ splitting induces rapid left lateral liver lobe hypertrophy enabling 2-staged extended right hepatic resection in small-for-size settings.Ann Surg. 2012; 256: e7-e8
- Playing Play-Doh to prevent postoperative liver failure.Ann Surg. 2012; 255: 415-417
- Early survival and safety of ALPPS: first report of the International ALPPS Registry.Ann Surg. 2014; 260: 829-836
- Effects of pirfenidone in acute and sub-chronic liver fibrosis, and an initiation-promotion cancer model in the mouse.Toxicol Appl Pharmacol. 2018; 339: 1-9
- IL6 Promotes compensatory liver regeneration in cirrhotic rat after partial hepatectomy.Cytokine. 2008; 42: 372-378
- The ALPPS in the treatment of hepatitis B-related hepatocellular carcinoma with cirrhosis: a single-center study and literature review.Surg Innov. 2017; 24: 358-364
- Totally laparoscopic ALPPS in the treatment of cirrhotic hepatocellular carcinoma.Surg Endosc. 2015; 29: 2800-2801
- ALPPS: from human to mice highlighting accelerated and novel mechanisms of liver regeneration.Ann Surg. 2014; 260: 839-846
- Development of an experimental model of portal vein ligation associated with parenchymal.Cir Esp. 2014; 92: 676-681
- Establishment of a rat model of portal vein ligation combined with in situ splitting.PLoS One. 2014; 9e105511
- Characterization of a porcine model for associating liver partition and portal vein ligation for a staged hepatectomy.HPB (Oxford). 2015; 17: 1130-1136
- A novel rat model of liver regeneration: possible role of cytokine induced neutrophil chemoattractant-1 in augmented liver regeneration.Ann Surg Innov Res. 2015; 9: 11
- Associated liver partition and portal vein ligation (ALPPS) vs selective portal vein ligation (PVL) for staged hepatectomy in a rat model. Similar regenerative response?.PLoS One. 2015; 10e0144096
- A preliminary study of ALPPS procedure in a rat model.Sci Rep. 2015; 5: 17567
- Establishment of a rat model: associating liver partition with portal vein ligation for staged hepatectomy.Surgery. 2016; 159: 1299-1307
- Rabbit model provides new insights in liver regeneration after transection with portal vein ligation.J Surg Res. 2017; 209: 242-251
- How much liver needs to be transected in ALPPS? A translational study investigating the concept of less invasiveness.Surgery. 2017; 161: 453-464
- Hedgehog pathway mediates early acceleration of liver regeneration induced by a novel two-staged hepatectomy in mice.J Hepatol. 2017; 66: 560-570
- A new technique for accelerated liver regeneration: an experimental study in rats.Surgery. 2017; 162: 233-247
- Histogram analyses of diffusion kurtosis indices and apparent diffusion coefficient in assessing liver regeneration after ALPPS and a comparative study with portal vein ligation.J Magn Reson Imaging. 2018; 47: 729-736
- Rapid liver hypertrophy after portal vein occlusion correlates with the degree of collateralization between lobes-a study in pigs.J Gastrointest Surg. 2018; 22: 203-213
- Milk fat globule-EGF factor 8, secreted by mesenchymal stem cells, protects against liver fibrosis in mice.Gastroenterology. 2017; 152: 1174-1186
- Applying the ARRIVE guidelines to an in vivo database.PLoS Biol. 2015; 13e1002151
- Histological grading and staging of chronic hepatitis.J Hepatol. 1995; 22: 696-699
- Maturity of associating liver partition and portal vein ligation for staged hepatectomy-derived liver regeneration in a rat model.World J Gastroenterol. 2018; 24: 1107-1119
- Hybrid periportal hepatocytes regenerate the injured liver without giving rise to cancer.Cell. 2015; 162: 766-779
- Direct reprogramming of hepatic myofibroblasts into hepatocytes in vivo attenuates liver fibrosis.Cell Stem Cell. 2016; 18: 797-808
- Hepatostat: liver regeneration and normal liver tissue maintenance.Hepatology. 2017; 65: 1384-1392
- ALPPS—where do we stand, where do we go? Eight recommendations from the first international expert meeting.Ann Surg. 2016; 263: 839-841
Published online: September 21, 2018
Accepted: August 8, 2018
Received in revised form: August 5, 2018
Received: April 12, 2018
This study was supported by the Public Welfare Technology Application Project of Zhejiang Province (Grant No. 2017C33043, Recipient: Wang Yifan).
© 2018 Published by Elsevier Inc.