Extrahepatic surgery in cirrhosis significantly increases portal pressure in preclinical animal models
- Background: Liver cirrhosis is a relevant comorbidity with increasing prevalence. Postoperative decompensation and development of complications in patients with cirrhosis remains a frequent clinical problem. Surgery has been discussed as a precipitating event for decompensation and complications of cirrhosis, but the underlying pathomechanisms are still obscure. The aim of this study was to analyze the role of abdominal extrahepatic surgery in cirrhosis on portal pressure and fibrosis in a preclinical model. Methods: Compensated liver cirrhosis was induced using tetrachlormethane (CCL4) inhalation and bile duct ligation (BDL) models in rats, non-cirrhotic portal hypertension by partial portal vein ligation (PPVL). Intestinal manipulation (IM) as a model of extrahepatic abdominal surgery was performed. 2 and 7 days after IM, portal pressure was measured in-vivo. Hydroxyproline measurements, Sirius Red staining and qPCR measurements of the liver were performed for evaluation of fibrosis development and hepatic inflammation. Laboratory parameters of liver function in serum were analyzed. Results: Portal pressure was significantly elevated 2 and 7 days after IM in both models of cirrhosis. In the non-cirrhotic model the trend was the same, while not statistically significant. In both cirrhotic models, IM shows strong effects of decompensation, with significant weight loss, elevation of liver enzymes and hypoalbuminemia. 7 days after IM in the BDL group, Sirius red staining and hydroxyproline levels showed significant progression of fibrosis and significantly elevated mRNA levels of hepatic inflammation compared to the respective control group. A progression of fibrosis was not observed in the CCL4 model. Conclusion: In animal models of cirrhosis with continuous liver injury (BDL), IM increases portal pressure, and development of fibrosis. Perioperative portal pressure and hence inflammation processes may be therapeutic targets to prevent post-operative decompensation in cirrhosis.
Author: | Johannes ChangORCiD, Jonathan Meinke, Moritz Geck, Marc Hebest, Nina Böhling, Ramona Christina Dolscheid, Birgit Stoffel-WagnerORCiDGND, Glen Kristiansen, Marcus Overhaus, Leon O. Peyman, Sabine KleinORCiD, Frank Erhard UschnerORCiDGND, Maximilian BrolORCiDGND, Tim Oliver Vilz, Philipp LingohrGND, Jörg C. KalffORCiDGND, Christian JansenGND, Christian P. StraßburgORCiDGND, Sven Wehner, Jonel TrebickaORCiDGND, Michael PraktiknjoORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-620292 |
DOI: | https://doi.org/10.3389/fphys.2021.720898 |
ISSN: | 1664-042X |
Parent Title (English): | Frontiers in physiology |
Publisher: | Frontiers Research Foundation |
Place of publication: | Lausanne |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2021/08/20 |
Date of first Publication: | 2021/08/20 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2022/05/18 |
Tag: | ACLF; HVPG; acute decompensation; cirrhosis; intestinal manipulation; portal pressure; surgery |
Volume: | 12 |
Issue: | art. 720898 |
Page Number: | 12 |
First Page: | 1 |
Last Page: | 12 |
Note: | JC was funded by grants from the Else-Kroener Fresenius Foundation (2014_Kolleg.05) and BONFOR research program of the University of Bonn (grant ID 2019-2-08). JT was supported by grants from the Deutsche Forschungsgemeinschaft (SFB TRR57 to P18, CRC 1382 A09), European Union's Horizon 2020 Research and Innovation Programme (Galaxy, No. 668031; MICROB-PREDICT, No. 825694; DECISION, No. 847949), Societal Challenges – Health, Demographic Change and Wellbeing (No. 731875), and Cellex Foundation (PREDICT). MP was funded by the Ernst-und-Berta Grimmke Foundation (No. 5/19) and BONFOR research program of the University of Bonn (grant ID 2020-2A-07 and 2021-2A-07). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. |
HeBIS-PPN: | 49586613X |
Institutes: | Medizin |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Sammlungen: | Universitätspublikationen |
Licence (German): | ![]() |