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Hepatectomy-Induced Alterations in Hepatic Perfusion and Function: Toward Multi-Scale Computational Modeling for a Better Prediction of Post-hepatectomy Liver Function

Liver resection causes marked perfusion alterations in the liver remnant both on the
organ scale (vascular anatomy) and on the microscale (sinusoidal blood flow on tissue
level). These changes in perfusion affect hepatic functions via direct alterations in blood
supply and drainage, followed by indirect changes of biomechanical tissue properties and
cellular function. Changes in blood flow impose compression, tension and shear forces
on the liver tissue. These forces are perceived by mechanosensors on parenchymal
and non-parenchymal cells of the liver and regulate cell-cell and cell-matrix interactions
as well as cellular signaling and metabolism. These interactions are key players in
tissue growth and remodeling, a prerequisite to restore tissue function after PHx. Their
dysregulation is associated with metabolic impairment of the liver eventually leading to
liver failure, a serious post-hepatectomy complication with high morbidity and mortality.
Though certain links are known, the overall functional change after liver surgery is
not understood due to complex feedback loops, non-linearities, spatial heterogeneities
and different time-scales of events. Computational modeling is a unique approach to
gain a better understanding of complex biomedical systems. This approach allows (i)
integration of heterogeneous data and knowledge on multiple scales into a consistent
view of how perfusion is related to hepatic function; (ii) testing and generating hypotheses
based on predictive models, which must be validated experimentally and clinically. In
the long term, computational modeling will (iii) support surgical planning by predicting surgery-induced perfusion perturbations and their functional (metabolic) consequences;
and thereby (iv) allow minimizing surgical risks for the individual patient. Here, we review
the alterations of hepatic perfusion, biomechanical properties and function associated
with hepatectomy. Specifically, we provide an overview over the clinical problem,
preoperative diagnostics, functional imaging approaches, experimental approaches in
animal models, mechanoperception in the liver and impact on cellular metabolism, omics
approaches with a focus on transcriptomics, data integration and uncertainty analysis,
and computational modeling on multiple scales. Finally, we provide a perspective on how
multi-scale computational models, which couple perfusion changes to hepatic function,
could become part of clinical workflows to predict and optimize patient outcome after
complex liver surgery.

Identiferoai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:89433
Date31 January 2024
CreatorsChrist, Bruno, Collatz, Maximilian, Dahmen, Uta, Herrmann, Karl-Heinz, Höpfl, Sebastian, König, Matthias, Lambers, Lena, Marz, Manja, Meyer, Daria, Radde, Nicole, Reichenbach, Jürgen R., Ricken, Tim, Tautenhahn, Hans-Michael
PublisherFrontiers Media S.A.
Source SetsHochschulschriftenserver (HSSS) der SLUB Dresden
LanguageEnglish
Detected LanguageEnglish
Typeinfo:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text
Rightsinfo:eu-repo/semantics/openAccess
Relation733868

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