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Portal hypertension in cirrhosis: Pathophysiological mechanisms and therapy

Portal hypertension, defined as increased pressure in the portal vein, develops as a consequence of increased intrahepatic vascular resistance due to the dysregulation of liver sinusoidal endothelial cells (LSECs) and hepatic stellate cells (HSCs), frequently arising from chronic liver diseases. Ext...

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Detalles Bibliográficos
Autores principales: Iwakiri, Yasuko, Trebicka, Jonel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8318926/
https://www.ncbi.nlm.nih.gov/pubmed/34337369
http://dx.doi.org/10.1016/j.jhepr.2021.100316
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author Iwakiri, Yasuko
Trebicka, Jonel
author_facet Iwakiri, Yasuko
Trebicka, Jonel
author_sort Iwakiri, Yasuko
collection PubMed
description Portal hypertension, defined as increased pressure in the portal vein, develops as a consequence of increased intrahepatic vascular resistance due to the dysregulation of liver sinusoidal endothelial cells (LSECs) and hepatic stellate cells (HSCs), frequently arising from chronic liver diseases. Extrahepatic haemodynamic changes contribute to the aggravation of portal hypertension. The pathogenic complexity of portal hypertension and the unsuccessful translation of preclinical studies have impeded the development of effective therapeutics for patients with cirrhosis, while counteracting hepatic and extrahepatic mechanisms also pose a major obstacle to effective treatment. In this review article, we will discuss the following topics: i) cellular and molecular mechanisms of portal hypertension, focusing on dysregulation of LSECs, HSCs and hepatic microvascular thrombosis, as well as changes in the extrahepatic vasculature, since these are the major contributors to portal hypertension; ii) translational/clinical advances in our knowledge of portal hypertension; and iii) future directions.
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spelling pubmed-83189262021-07-31 Portal hypertension in cirrhosis: Pathophysiological mechanisms and therapy Iwakiri, Yasuko Trebicka, Jonel JHEP Rep Review Portal hypertension, defined as increased pressure in the portal vein, develops as a consequence of increased intrahepatic vascular resistance due to the dysregulation of liver sinusoidal endothelial cells (LSECs) and hepatic stellate cells (HSCs), frequently arising from chronic liver diseases. Extrahepatic haemodynamic changes contribute to the aggravation of portal hypertension. The pathogenic complexity of portal hypertension and the unsuccessful translation of preclinical studies have impeded the development of effective therapeutics for patients with cirrhosis, while counteracting hepatic and extrahepatic mechanisms also pose a major obstacle to effective treatment. In this review article, we will discuss the following topics: i) cellular and molecular mechanisms of portal hypertension, focusing on dysregulation of LSECs, HSCs and hepatic microvascular thrombosis, as well as changes in the extrahepatic vasculature, since these are the major contributors to portal hypertension; ii) translational/clinical advances in our knowledge of portal hypertension; and iii) future directions. Elsevier 2021-06-04 /pmc/articles/PMC8318926/ /pubmed/34337369 http://dx.doi.org/10.1016/j.jhepr.2021.100316 Text en © 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Review
Iwakiri, Yasuko
Trebicka, Jonel
Portal hypertension in cirrhosis: Pathophysiological mechanisms and therapy
title Portal hypertension in cirrhosis: Pathophysiological mechanisms and therapy
title_full Portal hypertension in cirrhosis: Pathophysiological mechanisms and therapy
title_fullStr Portal hypertension in cirrhosis: Pathophysiological mechanisms and therapy
title_full_unstemmed Portal hypertension in cirrhosis: Pathophysiological mechanisms and therapy
title_short Portal hypertension in cirrhosis: Pathophysiological mechanisms and therapy
title_sort portal hypertension in cirrhosis: pathophysiological mechanisms and therapy
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8318926/
https://www.ncbi.nlm.nih.gov/pubmed/34337369
http://dx.doi.org/10.1016/j.jhepr.2021.100316
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