Inflammation and portal hypertension - The undiscovered country

Gautam Mehta, Thierry Gustot, Rajeshwar P. Mookerjee, Juan Carlos Garcia-Pagan, Michael B. Fallon, Vijay Shah, Richard Moreau, Rajiv Jalan

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Summary Portal hypertension has traditionally been viewed as a progressive process, involving ultrastructural changes including fibrosis, nodule formation, and vascular thrombosis, leading to increased intrahepatic resistance to flow. However, it is increasingly recognized that a significant component of this vascular resistance results from a dynamic process, regulated by complex interactions between the injured hepatocyte, the sinusoidal endothelial cell, the Kupffer cell and the hepatic stellate cell, which impact on sinusoidal calibre. Recent findings suggest these haemodynamic findings are most marked in patients with superimposed inflammation. The precise mechanisms for vascular dysfunction in cirrhosis with superimposed inflammation remain to be fully elucidated but several studies over the past decade have started to generate the hypothesis that inflammation may be a key mediator of the pathogenesis and severity of portal hypertension in this context. This review provides a comprehensive overview of the biological mechanisms for inflammation playing a key role in the severity of portal hypertension, and illustrates potential novel therapies that act by modifying these processes.

Original languageEnglish (US)
Pages (from-to)155-163
Number of pages9
JournalJournal of Hepatology
Volume61
Issue number1
DOIs
StatePublished - 2014

Fingerprint

Portal Hypertension
Inflammation
Blood Vessels
Fibrosis
Hepatic Stellate Cells
Kupffer Cells
Vascular Resistance
Hepatocytes
Thrombosis
Endothelial Cells
Hemodynamics
Therapeutics

Keywords

  • Cirrhosis
  • Inflammation
  • Liver failure
  • Portal hypertension
  • Variceal bleeding

ASJC Scopus subject areas

  • Hepatology

Cite this

Mehta, G., Gustot, T., Mookerjee, R. P., Garcia-Pagan, J. C., Fallon, M. B., Shah, V., ... Jalan, R. (2014). Inflammation and portal hypertension - The undiscovered country. Journal of Hepatology, 61(1), 155-163. https://doi.org/10.1016/j.jhep.2014.03.014

Inflammation and portal hypertension - The undiscovered country. / Mehta, Gautam; Gustot, Thierry; Mookerjee, Rajeshwar P.; Garcia-Pagan, Juan Carlos; Fallon, Michael B.; Shah, Vijay; Moreau, Richard; Jalan, Rajiv.

In: Journal of Hepatology, Vol. 61, No. 1, 2014, p. 155-163.

Research output: Contribution to journalArticle

Mehta, G, Gustot, T, Mookerjee, RP, Garcia-Pagan, JC, Fallon, MB, Shah, V, Moreau, R & Jalan, R 2014, 'Inflammation and portal hypertension - The undiscovered country', Journal of Hepatology, vol. 61, no. 1, pp. 155-163. https://doi.org/10.1016/j.jhep.2014.03.014
Mehta G, Gustot T, Mookerjee RP, Garcia-Pagan JC, Fallon MB, Shah V et al. Inflammation and portal hypertension - The undiscovered country. Journal of Hepatology. 2014;61(1):155-163. https://doi.org/10.1016/j.jhep.2014.03.014
Mehta, Gautam ; Gustot, Thierry ; Mookerjee, Rajeshwar P. ; Garcia-Pagan, Juan Carlos ; Fallon, Michael B. ; Shah, Vijay ; Moreau, Richard ; Jalan, Rajiv. / Inflammation and portal hypertension - The undiscovered country. In: Journal of Hepatology. 2014 ; Vol. 61, No. 1. pp. 155-163.
@article{37a30c48e54b45679a7ba485ae4978a1,
title = "Inflammation and portal hypertension - The undiscovered country",
abstract = "Summary Portal hypertension has traditionally been viewed as a progressive process, involving ultrastructural changes including fibrosis, nodule formation, and vascular thrombosis, leading to increased intrahepatic resistance to flow. However, it is increasingly recognized that a significant component of this vascular resistance results from a dynamic process, regulated by complex interactions between the injured hepatocyte, the sinusoidal endothelial cell, the Kupffer cell and the hepatic stellate cell, which impact on sinusoidal calibre. Recent findings suggest these haemodynamic findings are most marked in patients with superimposed inflammation. The precise mechanisms for vascular dysfunction in cirrhosis with superimposed inflammation remain to be fully elucidated but several studies over the past decade have started to generate the hypothesis that inflammation may be a key mediator of the pathogenesis and severity of portal hypertension in this context. This review provides a comprehensive overview of the biological mechanisms for inflammation playing a key role in the severity of portal hypertension, and illustrates potential novel therapies that act by modifying these processes.",
keywords = "Cirrhosis, Inflammation, Liver failure, Portal hypertension, Variceal bleeding",
author = "Gautam Mehta and Thierry Gustot and Mookerjee, {Rajeshwar P.} and Garcia-Pagan, {Juan Carlos} and Fallon, {Michael B.} and Vijay Shah and Richard Moreau and Rajiv Jalan",
year = "2014",
doi = "10.1016/j.jhep.2014.03.014",
language = "English (US)",
volume = "61",
pages = "155--163",
journal = "Journal of Hepatology",
issn = "0168-8278",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - Inflammation and portal hypertension - The undiscovered country

AU - Mehta, Gautam

AU - Gustot, Thierry

AU - Mookerjee, Rajeshwar P.

AU - Garcia-Pagan, Juan Carlos

AU - Fallon, Michael B.

AU - Shah, Vijay

AU - Moreau, Richard

AU - Jalan, Rajiv

PY - 2014

Y1 - 2014

N2 - Summary Portal hypertension has traditionally been viewed as a progressive process, involving ultrastructural changes including fibrosis, nodule formation, and vascular thrombosis, leading to increased intrahepatic resistance to flow. However, it is increasingly recognized that a significant component of this vascular resistance results from a dynamic process, regulated by complex interactions between the injured hepatocyte, the sinusoidal endothelial cell, the Kupffer cell and the hepatic stellate cell, which impact on sinusoidal calibre. Recent findings suggest these haemodynamic findings are most marked in patients with superimposed inflammation. The precise mechanisms for vascular dysfunction in cirrhosis with superimposed inflammation remain to be fully elucidated but several studies over the past decade have started to generate the hypothesis that inflammation may be a key mediator of the pathogenesis and severity of portal hypertension in this context. This review provides a comprehensive overview of the biological mechanisms for inflammation playing a key role in the severity of portal hypertension, and illustrates potential novel therapies that act by modifying these processes.

AB - Summary Portal hypertension has traditionally been viewed as a progressive process, involving ultrastructural changes including fibrosis, nodule formation, and vascular thrombosis, leading to increased intrahepatic resistance to flow. However, it is increasingly recognized that a significant component of this vascular resistance results from a dynamic process, regulated by complex interactions between the injured hepatocyte, the sinusoidal endothelial cell, the Kupffer cell and the hepatic stellate cell, which impact on sinusoidal calibre. Recent findings suggest these haemodynamic findings are most marked in patients with superimposed inflammation. The precise mechanisms for vascular dysfunction in cirrhosis with superimposed inflammation remain to be fully elucidated but several studies over the past decade have started to generate the hypothesis that inflammation may be a key mediator of the pathogenesis and severity of portal hypertension in this context. This review provides a comprehensive overview of the biological mechanisms for inflammation playing a key role in the severity of portal hypertension, and illustrates potential novel therapies that act by modifying these processes.

KW - Cirrhosis

KW - Inflammation

KW - Liver failure

KW - Portal hypertension

KW - Variceal bleeding

UR - http://www.scopus.com/inward/record.url?scp=84902674056&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84902674056&partnerID=8YFLogxK

U2 - 10.1016/j.jhep.2014.03.014

DO - 10.1016/j.jhep.2014.03.014

M3 - Article

C2 - 24657399

AN - SCOPUS:84902674056

VL - 61

SP - 155

EP - 163

JO - Journal of Hepatology

JF - Journal of Hepatology

SN - 0168-8278

IS - 1

ER -