81 - Freie Mitteilung
3. Juni 2022, 08:30 - 10:00, Panorama 4
Cirrhosis, a vascular disease? Preliminary results from a new experimental model
B. Moeckli1, G. Oldani1, A. Peloso1, L. A. Orci1, F. Slits1, Q. Gex1, N. D. Theise2, S. Lacotte1, C. Toso1, Presenter: B. Moeckli1 (1Geneva, 2New York)
Liver cirrhosis is a chronic, progressive disease with a myriad of different etiologies. Once established, cirrhosis is considered irreversible. We hypothesize that all different etiologies share a common vascular injury pattern that occurs early in the disease course. Two simultaneous insults to the liver vasculature are responsible for the initiation and progression of the fibrotic disease process. To test this hypothesis we developed a new experimental model.
Male adult C57Bl6 mice were subjected to the following procedures: 1) Partial ligation of the inferior vena cava (IVC) to a diameter of 0.6 mm to reduce the IVC by 70% and create an outflow obstruction. 2) Injection of 50µm microspheres in the portal vein to obstruct distal branches of the portal vein. Mice were sacrificed at 6 and 12 weeks after the intervention (n=5). Groups with a sham intervention, only partial ligation of the IVC or only portal embolization served as controls (n=7). The rate of fibrosis was assessed with an automated machine-learning tool in Masson Trichome stained tissue slides.
Mice subjected to portal embolization suffered from high mortality in the immediate postoperative period (30.4%). All other animals survived until sacrifice. Animals that underwent both procedures had an elevated serum bilirubin (14 vs 3.6 µmol/L, p=0.007), but none of the animals developed ascites. 40% and 60% of animals developed macroscopic nodular liver disease at 6 and 12 weeks respectively. Mice developed progressive liver fibrosis at 12 weeks (2.84 vs 0.13%, p=4.5e-5) compared to 6 weeks (1.36 vs 0.13%, p =5.9e-4). Animals with both microscopic venous congestion and presence of microspheres in distal branches of the portal vein exhibited the highest percentage of fibrosis (3.53 vs 0.41% fibrosis, p =0.0018).
The results of our preliminary study highlight the importance of vascular processes in the development of liver cirrhosis. This could potentially provide a therapeutic target, common to all underlying etiologies of liver cirrhosis.