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

Zugehörigkeit
Cell Transplantation/Molecular Hepatology Lab, Department of Visceral, Transplant, Thoracic and Vascular Surgery, University of Leipzig Medical Center ,Leipzig ,Germany
Christ, Bruno;
GND
1214760317
Zugehörigkeit
RNA Bioinformatics and High-Throughput Analysis, Faculty of Mathematics and Computer Science, Friedrich Schiller University Jena
Collatz, Maximilian;
GND
114498405X
ORCID
0000-0003-3483-3388
Zugehörigkeit
Experimental Transplantation Surgery, Department of General, Visceral and Vascular Surgery, Jena University Hospital
Dahmen, Uta;
GND
123420628
Zugehörigkeit
Medical Physics Group, Institute of Diagnostic and Interventional Radiology, Jena University Hospital
Herrmann, Karl-Heinz;
Zugehörigkeit
Faculty of Engineering Design, Production Engineering and Automotive Engineering, Institute for Systems Theory and Automatic Control, University of Stuttgart ,Stuttgart ,Germany
Höpfl, Sebastian;
Zugehörigkeit
Systems Medicine of the Liver Lab, Institute for Theoretical Biology, Humboldt-University Berlin ,Berlin ,Germany
König, Matthias;
Zugehörigkeit
Faculty of Aerospace Engineering and Geodesy, Institute of Mechanics, Structural Analysis and Dynamics, University of Stuttgart ,Stuttgart ,Germany
Lambers, Lena;
GND
140462732
ORCID
0000-0003-4783-8823
Zugehörigkeit
RNA Bioinformatics and High-Throughput Analysis, Faculty of Mathematics and Computer Science, Friedrich Schiller University Jena
Marz, Manja;
GND
122155493X
ORCID
0000-0003-2006-4610
Zugehörigkeit
RNA Bioinformatics and High-Throughput Analysis, Faculty of Mathematics and Computer Science, Friedrich Schiller University Jena
Meyer, Daria;
Zugehörigkeit
Faculty of Engineering Design, Production Engineering and Automotive Engineering, Institute for Systems Theory and Automatic Control, University of Stuttgart ,Stuttgart ,Germany
Radde, Nicole;
GND
172628067
Zugehörigkeit
Medical Physics Group, Institute of Diagnostic and Interventional Radiology, Jena University Hospital
Reichenbach, Jürgen R.;
Zugehörigkeit
Faculty of Aerospace Engineering and Geodesy, Institute of Mechanics, Structural Analysis and Dynamics, University of Stuttgart ,Stuttgart ,Germany
Ricken, Tim;
GND
1044672463
Zugehörigkeit
Department of General, Visceral and Vascular Surgery, Jena University Hospital
Tautenhahn, Hans-Michael

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.

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Rechteinhaber: Copyright © 2021 Christ, Collatz, Dahmen, Herrmann, Höpfl, König, Lambers, Marz, Meyer, Radde, Reichenbach, Ricken and Tautenhahn.

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