TY  - JOUR
A1  - Chang, Johannes
A1  - Meinke, Jonathan
A1  - Geck, Moritz
A1  - Hebest, Marc
A1  - Böhling, Nina
A1  - Dolscheid, Ramona Christina
A1  - Stoffel-Wagner, Birgit
A1  - Kristiansen, Glen
A1  - Overhaus, Marcus
A1  - Peyman, Leon O.
A1  - Klein, Sabine
A1  - Uschner, Frank Erhard
A1  - Brol, Maximilian
A1  - Vilz, Tim Oliver
A1  - Lingohr, Philipp
A1  - Kalff, Jörg C.
A1  - Jansen, Christian
A1  - Straßburg, Christian P.
A1  - Wehner, Sven
A1  - Trebicka, Jonel
A1  - Praktiknjo, Michael
T1  - Extrahepatic surgery in cirrhosis significantly increases portal pressure in preclinical animal models
T2  - Frontiers in physiology
N2  - 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.
KW  - surgery
KW  - acute decompensation
KW  - cirrhosis
KW  - ACLF
KW  - portal pressure
KW  - HVPG
KW  - intestinal manipulation
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/62029
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-620292
SN  - 1664-042X
N1  - 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.
VL  - 12
IS  - art. 720898
SP  - 1
EP  - 12
PB  - Frontiers Research Foundation
CY  - Lausanne
ER  -