New cellular and molecular targets for the treatment of portal hypertension

Portal hypertension (PH) is a common complication of chronic liver disease, and it determines most complications leading to death or liver transplantation in patients with liver cirrhosis. PH results from increased resistance to portal blood flow through the cirrhotic liver. This is caused by two me...

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Veröffentlicht in:Hepatology international 2015-04, Vol.9 (2), p.183-191
Hauptverfasser: Gracia-Sancho, Jordi, Maeso-Díaz, Raquel, Fernández-Iglesias, Anabel, Navarro-Zornoza, María, Bosch, Jaime
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container_end_page 191
container_issue 2
container_start_page 183
container_title Hepatology international
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creator Gracia-Sancho, Jordi
Maeso-Díaz, Raquel
Fernández-Iglesias, Anabel
Navarro-Zornoza, María
Bosch, Jaime
description Portal hypertension (PH) is a common complication of chronic liver disease, and it determines most complications leading to death or liver transplantation in patients with liver cirrhosis. PH results from increased resistance to portal blood flow through the cirrhotic liver. This is caused by two mechanisms: (a) distortion of the liver vascular architecture and (b) hepatic microvascular dysfunction. Increment in hepatic resistance is latterly accompanied by splanchnic vasodilation, which further aggravates PH. Hepatic microvascular dysfunction occurs early in the course of chronic liver disease as a consequence of inflammation and oxidative stress and determines loss of the normal phenotype of liver sinusoidal endothelial cells (LSEC). The cross-talk between LSEC and hepatic stellate cells induces activation of the latter, which in turn proliferate, migrate and increase collagen deposition around the sinusoids, contributing to fibrogenesis, architectural disruption and angiogenesis. Therapy for PH aims at correcting these pathophysiological abnormalities: liver injury, fibrogenesis, increased hepatic vascular tone and splanchnic vasodilatation. Continuing liver injury may be counteracted specifically by etiological treatments, while architectural disruption and fibrosis can be ameliorated by a variety of anti-fibrogenic drugs and anti-angiogenic strategies. Sinusoidal endothelial dysfunction is ameliorated by statins and other drugs increasing NO availability. Splanchnic hyperemia can be counteracted by non-selective beta-blockers (NSBBs), vasopressin analogs and somatostatin analogs. Future treatment of portal hypertension will evolve to use etiological treatments together with anti-fibrotic agents and/or drugs improving microvascular function in initial stages of cirrhosis (pre-primary prophylaxis), while NSBBs will be added in advanced stages of the disease.
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subjects Acetates - therapeutic use
Antioxidants - therapeutic use
Biopterins - analogs & derivatives
Biopterins - therapeutic use
Chenodeoxycholic Acid - analogs & derivatives
Chenodeoxycholic Acid - therapeutic use
Colorectal Surgery
Cyclopropanes
Endothelial Cells - drug effects
Hepatology
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use
Hypertension, Portal - drug therapy
Hypertension, Portal - etiology
Hypertension, Portal - physiopathology
Leukotriene Antagonists - therapeutic use
Liver Circulation - drug effects
Liver Cirrhosis - complications
Liver Cirrhosis - drug therapy
Medicine
Medicine & Public Health
Microvessels - drug effects
Microvessels - physiopathology
Molecular Targeted Therapy
Naphthalenes - therapeutic use
Neovascularization, Pathologic - drug therapy
Propionates - therapeutic use
Quinolines - therapeutic use
Review Article
Sulfides
Surgery
Vascular Resistance - drug effects
title New cellular and molecular targets for the treatment of portal hypertension
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