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Quantitative analysis of hepatic macro- and microvascular alterations during cirrhogenesis in the rat.

  • Peeters, Geert1
  • Debbaut, Charlotte1
  • Friebel, Adrian2, 3
  • Cornillie, Pieter4
  • De Vos, Winnok H5, 6
  • Favere, Kasper1
  • Vander Elst, Ingrid7
  • Vandecasteele, Tim4
  • Johann, Tim2, 8
  • Van Hoorebeke, Luc9
  • Monbaliu, Diethard10, 11
  • Drasdo, Dirk2, 8, 12
  • Hoehme, Stefan2, 3
  • Laleman, Wim7, 13
  • Segers, Patrick1
  • 1 IBiTech - bioMMeda, Department of Electronics and Information Systems, Ghent University, Gent, Belgium. , (Belgium)
  • 2 Interdisciplinary Centre for Bioinformatics (IZBI), University of Leipzig, Leipzig, Germany. , (Germany)
  • 3 Institute of Computer Science, University of Leipzig, Leipzig, Germany. , (Germany)
  • 4 Department of Morphology, Faculty of Veterinary Medicine, Ghent University, Gent, Belgium. , (Belgium)
  • 5 Laboratory of Cell Biology and Histology, Department of Veterinary Sciences, University of Antwerp, Antwerp, Belgium. , (Belgium)
  • 6 Cell Systems and Imaging, Department of Molecular Biotechnology, University of Ghent, Gent, Belgium. , (Belgium)
  • 7 Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium. , (Belgium)
  • 8 LJLL, INRIA Paris & Sorbonne Universités UPMC Univ Paris 6, Paris, France. , (France)
  • 9 Centre for X-Ray Tomography, Department of Physics and Astronomy, Ghent University, Gent, Belgium. , (Belgium)
  • 10 Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium. , (Belgium)
  • 11 Department of Abdominal Transplant Surgery, University Hospitals Leuven, Leuven, Belgium. , (Belgium)
  • 12 Leibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund, Dortmund, Germany. , (Germany)
  • 13 Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium. , (Belgium)
Published Article
Journal of anatomy
Publication Date
Mar 01, 2018
DOI: 10.1111/joa.12760
PMID: 29205328


Cirrhosis represents the end-stage of any persistent chronically active liver disease. It is characterized by the complete replacement of normal liver tissue by fibrosis, regenerative nodules, and complete fibrotic vascularized septa. The resulting angioarchitectural distortion contributes to an increasing intrahepatic vascular resistance, impeding liver perfusion and leading to portal hypertension. To date, knowledge on the dynamically evolving pathological changes of the hepatic vasculature during cirrhogenesis remains limited. More specifically, detailed anatomical data on the vascular adaptations during disease development is lacking. To address this need, we studied the 3D architecture of the hepatic vasculature during induction of cirrhogenesis in a rat model. Cirrhosis was chemically induced with thioacetamide (TAA). At predefined time points, the hepatic vasculature was fixed and visualized using a combination of vascular corrosion casting and deep tissue microscopy. Three-dimensional reconstruction and data-fitting enabled cirrhogenic features to extracted at multiple scales, portraying the impact of cirrhosis on the hepatic vasculature. At the macrolevel, we noticed that regenerative nodules severely compressed pliant venous vessels from 12 weeks of TAA intoxication onwards. Especially hepatic veins were highly affected by this compression, with collapsed vessel segments severely reducing perfusion capabilities. At the microlevel, we discovered zone-specific sinusoidal degeneration, with sinusoids located near the surface being more affected than those in the middle of a liver lobe. Our data shed light on and quantify the evolving angioarchitecture during cirrhogenesis. These findings may prove helpful for future targeted invasive interventions. © 2017 Anatomical Society.

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