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. 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.
Metadaten
Author:Yasuko IwakiriORCiD, Jonel TrebickaORCiDGND
URN:urn:nbn:de:hebis:30:3-630837
DOI:https://doi.org/10.1016/j.jhepr.2021.100316
ISSN:2589-5559
Parent Title (English):JHEP reports
Publisher:Elsevier
Place of publication:Amsterdam
Document Type:Article
Language:English
Date of Publication (online):2021/06/04
Date of first Publication:2021/06/04
Publishing Institution:Universit├Ątsbibliothek Johann Christian Senckenberg
Release Date:2022/07/11
Tag:FXR; HSC; LSEC; NO; NSBB; Rho-kinase; TIPS; VEGF; angiogenesis; fibrosis; liver stiffness; statins
Volume:3.2021
Issue:4, art. 100316
Article Number:100316
Page Number:14
First Page:1
Last Page:14
Note:
NIH grants (R01DK117597, 1R01AA025342 and R56DK121511) to YI and Deutsche Forschungsgemeinschaft (SFB TRR57 to P18, CRC 1382 to A09), European Union's Horizon 2020 Research and Innovation Programme (Galaxy, No. 668031; MICROB-PREDICT, No. 825694; DECISION, No. 847949), Eurostars (DeFiber, E!12350), IK and Societal Challenges - Health, Demographic Change and Wellbeing (LIVERHOPE, No. 731875), and Cellex Foundation (PREDICT) to JT.
HeBIS-PPN:501828281
Institutes:Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universit├Ątspublikationen
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell - Keine Bearbeitung 4.0