Sinusoidal Cells in Liver Diseases

Role in their Pathophysiology, Diagnosis, and Treatment

1st Edition - April 9, 2024
Imprint: Academic Press
Editor: Jordi Gracia-Sancho
Language: English
Paperback ISBN:
9 7 8 - 0 - 3 2 3 - 9 5 2 6 2 - 0
eBook ISBN:
9 7 8 - 0 - 3 2 3 - 9 5 2 6 3 - 7

Sinusoidal Cells in Liver Diseases: Role in their Pathophysiology, Diagnosis, and Treatment provides a state-of-the-art review on recent advances surrounding the role of liver sin… Read more

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Sinusoidal Cells in Liver Diseases: Role in their Pathophysiology, Diagnosis, and Treatment provides a state-of-the-art review on recent advances surrounding the role of liver sinusoidal cells (LSECs, HSCs, macrophages, and other non-parenchymal cells) in acute and chronic liver diseases. Coverage emphasizes disease pathophysiology, novel mechanisms, unmet clinical questions, development of biomarkers, and treatment opportunities. By focusing on the role of sinusoidal cells in human liver diseases, this reference provides a comprehensive overview of the role of sinusoidal cells in acute and chronic liver diseases, in its pathophysiology and mechanisms, and in the development of novel biomarkers and new therapeutics.

Cells of the liver vasculature play an essential role in the pathophysiology of acute and chronic liver diseases and are considered key therapeutic targets to treat most of human hepatopathies. Coverage in this reference includes the phenotypic changes occurring in liver vascular cells and how cells contribute to the development of microcirculatory dysfunction, fibrosis, inflammation, and liver failure.

Cover image
Title page
Table of Contents
Copyright
Dedication
Contributors
About the editor
Preface
Section I. The liver sinusoid — General concepts
Chapter 1. The unique architecture of the hepatic sinusoid
1. Liver sinusoidal endothelial cells
2. Kupffer cells
3. Hepatic stellate cells
4. Extracellular matrix and sinusoidal structures
Chapter 2. Sinusoidal cell interactions—From soluble factors to exosomes
1. Introduction
2. Communication of sinusoidal cells during homeostasis
3. Role of soluble factors in liver disease
4. Cross-talk between different sinusoidal cells via exosomes in the spectrum of liver disease
5. Conclusions and future perspectives
Abbreviations
Chapter 3. Sinusoidal cells and liver immunology
1. Liver as an immune organ
2. Sinusoidal cells involved in liver immunity
3. Conclusion
Chapter 4. Liver sinusoidal cells in aging
1. Introduction
2. The hepatic sinusoid in young, healthy individuals
3. Impact of aging on the hepatic sinusoid
4. Molecular mechanisms underlying age-related changes in the hepatic sinusoid
5. Clinical implications of age-related changes in the hepatic sinusoid
6. Future directions for research on aging and the hepatic sinusoid
7. Conclusions
Chapter 5. Microscopic imaging of hepatic sinusoidal cells: Fifty years in the making
1. Introduction
2. The liver and its primary cells—Hepatic parenchymal cells
3. Liver sinusoidal cells
4. Emerging microscopy approaches
5. Conclusion and outlook
Chapter 6. The liver sinusoid at single-cell level
1. Introduction
2. Single-cell technologies and analytics
3. The homeostatic liver sinusoid at single-cell resolution
4. Single-cell analysis of the sinusoid during acute liver injury and regeneration
5. Sinusoidal responses to chronic liver injury and fibrosis at single-cell resolution
6. Single-cell analysis of sinusoidal cells in liver cancer
7. Future directions
8. Conclusions
Chapter 7. Advanced models to study liver sinusoids
1. Introduction
2. 3D bioengineered models
3. 3D bioprinting
4. Liver-on-a-chip
5. Spheroids and organoids
6. Precision-cut liver slices
7. Animal models
8. Conclusion
Chapter 8. Strategies to target and genetically modify the liver sinusoid
1. The liver sinusoidal endothelial cell
2. Genetic disorders of the LSEC
3. Gene therapy
4. Delivery approaches
5. Targeting the LSEC
6. Conclusion
Abbreviations
Section II. The liver sinusoid in acute liver injury
Chapter 9. Drug-induced liver injury
1. The hepatic sinusoid
2. Liver sinusoidal endothelial cells
3. Drug-induced liver injury: Background
4. Experimenting with LSECs
5. Therapy targeting LSECs in DILI
6. Conclusion
Abbreviations
Chapter 10. The liver sinusoid in ischemia–reperfusion injury and regeneration
1. Introduction
2. Liver sinusoid in I/R injury
3. Liver sinusoid in regeneration
4. Therapeutic approaches to reduce I/R injury and enhance regeneration
5. Conclusion
Chapter 11. Acute bacterial and viral infections
1. The liver, a target of multiple microorganisms
2. Liver cells responding to microbial cargo
3. Kupffer cells, threat sinusoidal sensors
4. LSECs, immunological doors to the liver parenchyma
5. Dendritic cells, professional immune events planners
6. Liver-resident lymphocytes, immune warhorses
7. Innate lymphoid cells, the innate lymphocyte mimos
8. Hepatic stellate cells, double-edged swords
9. Pathogen infections in chronic liver disease
10. Future directions
Abbreviations
Section III. The liver sinusoid in chronic liver disease
Chapter 12. The liver sinusoid in chronic liver disease: NAFLD and NASH
1. Introduction and general overview
2. Mechanisms of altered intrahepatic vascular resistance in NAFLD disease progression
3. Structural alterations
4. Functional alterations
5. Other nonvascular alterations in liver sinusoids
6. Current (investigational) therapies and liver vascular dysfunction in NAFLD
7. Conclusions and other considerations
Abbreviations
Chapter 13. Liver Sinusoidal Cells in alcohol-associated liver disease
1. Introduction
2. Alcohol metabolism by LSECs
3. LSEC dysfunction in ALD
4. LSEC hyperactivation in ALD
5. The reticuloendothelial system in ALD
6. Interleukin-6 signaling in ALD
7. Conclusion
Chapter 14. Liver fibrosis
1. Introduction
2. LSECs in liver fibrosis initiation
3. LSECs in liver fibrosis progression
4. LSECs during liver fibrosis regression
5. Targeting LSECs: A novel approach in antifibrogenic therapy
6. Conclusions
Chapter 15. Portal hypertension
1. The portal hypertension syndrome. Definition, etiology, classification
2. The consequences of portal hypertension
3. Evaluation of portal hypertension
4. Pathophysiology of portal hypertension: Targets for therapy
5. Rationale targets for therapy
Chapter 16. The liver sinusoid in acute-on-chronic liver failure
1. Introduction
2. Mechanisms of ACLF
3. Role of liver sinusoidal endothelial cells
4. Role of immune cells
5. Role of HSC/fibrosis
6. Role of hepatocyte damage
7. Potential therapies
8. Conclusions
Chapter 17. Liver cancer
1. Introduction
2. Hepatic sinusoidal cells in liver cancer
3. Cross-talk between hepatic sinusoidal cells and the tumor microenvironment
4. Significance of hepatic sinusoidal cells in HCC therapy
5. Conclusion
Chapter 18. Sinusoidal cells in liver metastasis
1. Introduction
2. Tumor microenvironment of liver metastasis
3. Liver nonparenchymal cells
4. Clinical intervention
5. Conclusions
Abbreviations
Chapter 19. Cholestatic diseases
1. Anatomy and embryology of the biliary tree
2. Morphological modifications of the biliary tree in regenerative conditions
3. Physiology of the biliary epithelium
4. Sinusoidal endothelial cell signaling and dysfunction in cholestasis: experimental models
5. Data on human chronic cholestatic liver diseases
6. Human findings linking sinusoidal endothelium and chronic cholestatic disease
7. Conclusions
Section IV. The liver sinusoid in other vascular diseases
Chapter 20. Liver vascular malformations
1. Hereditary hemorrhagic telangiectasia
2. Congenital portosystemic shunts
Chapter 21. Liver sinusoidal endothelial cells in congestive hepatopathy
1. Introduction
2. The vascular anatomy of the liver and hepatic sinusoids
3. Clinical presentation
4. Pathophysiology of congestive hepatopathy
5. Models of congestive hepatopathy
6. The contribution of LSECs to HCC in congestive hepatopathy
7. Conclusion and future directions
Abbreviations
Chapter 22. Porto-sinusoidal vascular disorder
1. Introduction
2. Present definition and diagnosis criteria
3. Epidemiology
4. Associated conditions
5. Pathophysiology
6. Research tools
7. Clinical features
8. Natural history
9. Diagnostic methods
10. Medical management
11. Quality of life
12. Current and future perspectives in translational and clinical
13. Conclusions
Abbreviations
Section V. Liver sinusoidal cells in the diagnosis and treatment of liver diseases
Chapter 23. Role of liver sinusoidal endothelial cells in the diagnosis and treatment of liver diseases
1. Introduction
2. Role of liver sinusoidal endothelial cells in the diagnosis of liver diseases
3. Role of liver sinusoidal endothelial cells in the treatment of liver diseases
Chapter 24. Role of Kupffer cells and other immune cells
1. Role of immune cells for diagnosis of liver disease and prognosis prediction
2. Role of macrophages for treatment of liver disease
3. Targeting the local microenvironment, intercellular cross-talk, and other immune cells
4. Challenges and perspectives of immune cell–based therapeutic approaches
Chapter 25. Liver sinusoidal cells in the diagnosis and treatment of liver diseases: Role of hepatic stellate cells
1. Evaluation of liver fibrosis and definition of different types of fibrogenesis in various conditions
2. Static versus dynamic process: Reversibility of hepatic fibrosis and cirrhosis
3. Diagnosis and noninvasive assessment of chronic liver disease
4. The HSCs and the other fibroblasts—Myofibroblasts
5. Target discovery and validation: Clinical studies in HSC as primary target for antifibrotic agents
6. Target discovery and validation: Focus on ECM—A dynamic partner of HSCs in liver diseases
7. Target discovery and validation: Focus on ECM biomechanical properties and composition—Dynamic partners of HSCs in liver diseases
8. Conclusion and future
Index

Jordi Gracia-Sancho

Jordi Gracia-Sancho is the Chief of the Liver Vascular Biology Research Group at the IDIBAPS Research Institute – Hospital Clínic de Barcelona, Associate Researcher at the Department of Visceral Surgery and Medicine – University of Bern, & Scientific Director of the Spanish Research Consortium on Liver & Digestive Diseases (CIBEREHD).

He graduated in Biochemistry receiving undergraduate research training in basic hemochromatosis at the London Metropolitan University, pursued pre-doctoral studies in basic portal hypertension at the University of Barcelona Medical School, and post-doctoral training at the Center for Excellence in Vascular Biology - Harvard Medical School & Brigham and Women’s Hospital. In 2012 he obtained the “Ramón y Cajal” Spanish tenure-track position and then promoted to his current senior position.

Jordi’s research focuses on liver vascular pathobiology with special interest in the role of sinusoidal cells, and their interactions, in acute and chronic liver diseases, and in aging. He (co-)authored more than 125 peer-reviewed original papers and reviews, and currently serves as Associate Editor for the Journal of Hepatology. In addition, he is invited professor in different universities within Spain and Europe and co-leads diverse educational initiatives including the LiverSeminars Program (www.liverseminars.eu), the 2018 EASL-Basic School of Hepatology, the 2020 APASL-Symposium on Regression of Portal Hypertension, the 2020 AASLD-Symposium on Senescence and Liver Diseases, the 2021 EASL-Symposium on Sinusoidal Cells in Liver Diseases and the 2023 AMH-Irwin Arias Symposium.

Prof Gracia has been invited speaker in different national and international conferences, including the annual meetings of the European, American and Asia-Pacific associations of Hepatology. He has been member of the Scientific Committee of the Spanish Association for the Study of the Liver (AEEH) and the Steering Committee of the Portal Hypertension Special Interest Group of the American Association for the Study of Liver Diseases (AASLD). He is now member of the Governing Board of AEEH, the Basic Research Committee of AASLD and the Baveno Cooperation Steering Committee. In 2016 he received the Emerging Leader Award from the European Association for the Study of the Liver (EASL). He served as Scientific Secretary of the International Society for Hepatic Sinusoidal Research (ISHSR) from 2017-2022, being now the President-Elect of this Society.

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