PhD Scientific Days 2022

Budapest, 6-7 July 2022

Clinical Medicine I. (Poster discussion will take place in the Aula during the Coffee Break)

The role of farnesoid X receptor in induced liver regeneration

Noémi Daradics 1; Pim B Olthof 2; András Budai 3; Michal Heger 4,5; Thomas M van Gulik 6; András Fülöp 1; Attila Szijártó 1

1 Department of Surgery, Transplantation and Interventional Gastroenterology, Semmelweis University
2 Erasmus Medical Center, Department of Surgery, Rotterdam, The Netherlands
3 2nd Department of Pathology, Semmelweis University
4 Jiaxing Key Laboratory for Photonanomedicine and Experimental Therapeutics, Department of Pharmaceutics, College of Medicine, Jiaxing University, China
5 Laboratory of Experimental Oncology, Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands
6 Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands

Text of the abstract

Introduction: In cases of multiplex or large liver tumors the only curative treatment is liver resection, however the volume of the future liver remnant (FLR) is usually not appropriate, which could lead to a posthepatectomy liver failure. ALPPS (Associating Liver Partition and Portal vein ligation for Staged hepatectomy) is a two-staged hepatectomy, which could facilitate liver regeneration, resulting a sufficient FLR within a short time compared to PVL (Portal Vein Ligation). Although the effect of the hepatic and the ileal pathways of the farnesoid X receptors (FXR) in liver regeneration are significant, they have not yet been studied following the ALPPS, while their effect in case of PVL is already studied.
Aims: Studying the role of FXR pathways during liver regeneration induced by ALPPS.
Methods: 60 male Wistar rats underwent portal vein ligation (PVL) (n=30) or ALPPS (n=30). The animals were sacrificed after 0 (without surgery), 24, 48, 72, and 168 postoperative hours. The regeneration rate, Ki67 index, hemodynamic changes in the hepatic circulation, and bile acid (BA) levels were examined. Moreover molecular regulators of the FXR signaling pathway, BA transport, and BA production were analyzed.
Result: The liver regeneration, Ki67 index, and the increase of systemic and portal BA levels were significantly higher in the ALPPS groups compared to the PVL groups. Furthermore there were substantial differences in the mRNA levels of the hepatic FXR pathway between the ALPPS and PVL groups. The mRNA levels of the ileal FXR pathway were significantly higher in the 24 postoperative hour following the ALPPS.
Conclusion: We revealed a potential contiguity between FXR signaling pathway and triggered liver regeneration. Following ALPPS the liver regeneration could be accelerated by intestinal FXR pathway instead of hepatic FXR pathway.
Funding: This study was supported by the Semmelweis University 250+ PhD Excellence Grant (EFOP-3.6.3-VEKOP-16-2017 00009).