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Extrahepatic Surgery in Cirrhosis Significantly Increases Portal Pressure in Preclinical Animal Models

Authors: Johannes Chang; Jonathan Meinke; Moritz Geck; Marc Hebest; Nina Böhling; Ramona Dolscheid-Pommerich; Birgit Stoffel-Wagner; +15 Authors

Extrahepatic Surgery in Cirrhosis Significantly Increases Portal Pressure in Preclinical Animal Models

Abstract

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.

Country
Germany
Subjects by Vocabulary

Microsoft Academic Graph classification: medicine.medical_specialty Cirrhosis Portal venous pressure Fibrosis medicine Decompensation Hypoalbuminemia Liver injury business.industry medicine.disease Surgery Portal hypertension Liver function business

Dewey Decimal Classification: ddc:610

Keywords

portal pressure, intestinal manipulation, Physiology, surgery, ACLF, Physiology (medical), QP1-981, Original Research, cirrhosis, acute decompensation, HVPG

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    Average
  • citations
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    5
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Average
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Average
    Powered byBIP!BIP!
Powered by OpenAIRE graph
Found an issue? Give us feedback
citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
5
Top 10%
Average
Average
Funded by
EC| MICROB-PREDICT
Project
MICROB-PREDICT
MICROBiome-based biomarkers to PREDICT decompensation of liver cirrhosis and treatment response
  • Funder: European Commission (EC)
  • Project Code: 825694
  • Funding stream: H2020 | RIA
Validated by funder
,
EC| DECISION
Project
DECISION
DECOMPENSATED CIRRHOSIS: IDENTIFICATION OF NEW COMBINATORIAL THERAPIES BASED ON SYSTEMS APPROACHES
  • Funder: European Commission (EC)
  • Project Code: 847949
  • Funding stream: H2020 | RIA
Validated by funder | iis
,
EC| GALAXY
Project
GALAXY
GALAXY: Gut-and-liver axis in alcoholic liver fibrosis
  • Funder: European Commission (EC)
  • Project Code: 668031
  • Funding stream: H2020 | RIA
Validated by funder | iis
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