Emergence - Emergence

MICROparticles for predicting clinically Significant Portal hYpertension – MICRO-SPY

Interest of circulating microparticles to estimate portal hypertension

Our preliminary results show that plasma levels of leuko-endothelial and hepatocyte microparticle are increased in patients with cirrhosis and induce vascular dilation, a process knwon to contribute to portal hypertension. <br />

Can circulating microparticle levels help estimate portal pressure?

Cirrhosis affects between 130'000 and 214'000 persons in France. Portal hypertension is a frequent consequence of cirrhosis, and strongly contributes to the main complications of cirrhosis. Hepatic venous pressure gradient is an accurate way of measuring portal pressure in patients with cirrhosis but is invasive and available only in expert centers. There is thus a need for accurate non invasive methods allowing for predicting clinically significant portal hypertension. Microparticles are extracellular vesicles. We have obtained data showing that plasma levels of leuko-endothelial and hepatocyte microparticles are increased in patients with cirrhosis and that these microparticles induce vascular dilation, a key mechanism of portal hypertension. We propose here to establish a routine analysis of circulating leukocyte, endothelial and hepatocyte MP levels to estimate portal pressure in cirrhosis. <br />

We propose here to establish a routine analysis of circulating leukocyte, endothelial and hepatocyte MP levels. Then, we will evaluate the predicting value of these plasma MPs for HVPG in 500 well-characterized patients with cirrhosis.

We have already included 250 patients.

250 patients have already been included. We expect 250 additionnal patients over the next year.

A patent has been submitted

Liver disease is the European Union's 5th biggest killer. Cirrhosis, a consequence of chronic liver diseases, is one major cause of death in chronic liver disease patients. Prevalence of cirrhosis in France is estimated between 130'000 and 214'000 persons. Portal hypertension is a frequent complication of cirrhosis, and strongly contributes to the main complications of cirrhosis, i.e. gastrointestinal bleedings, ascites and hepatic encephalopathy. Hepatic venous pressure gradient (HVPG) is an accurate way of measuring portal pressure in patients with cirrhosis. An HVPG at 10 mmHg or higher, defines the ‘‘clinically significant portal hypertension’’ and has been well demonstrated as having an independent prognostic value for most relevant events in the course of cirrhosis, and particularly for complications of portal hypertension. HVPG can impact on therapeutic choices. However, HVPG measurement is invasive and available only in expert centers. There is thus a need for accurate non invasive methods allowing for predicting clinically significant portal hypertension.
Microparticles (MPs) are membrane vesicles with a diameter ranging from 0.1 to 1 µm, released in extracellular space following cell activation or apoptosis. Liver diseases are associated with increased liver cell apoptosis and activation. We have obtained data showing that plasma levels of leuko-endothelial and hepatocyte MPs are increased in patients with cirrhosis. These MPs induce an arterial hyporesponse to vascoconstrictors, a key mechanism of portal hypertension. Circulating leuko-endothelial MP levels also predict survival in cirrhosis patients. These preliminary results thus strongly suggest that plasma leuko-endothelial and hepatocyte MP levels could predict clinically significant portal hypertension. We propose here to establish a routine analysis of circulating leukocyte, endothelial and hepatocyte MP levels. Then, we will evaluate the predicting value of these plasma MPs for HVPG in 500 well-characterized patients with cirrhosis.

Project coordinator

Monsieur Pierre-Emmanuel RAUTOU (Paris-Cardiovascular research Center, team 1: Microparticles : Bioactive Markers in Atheroscerosis ) – pierre-emmanuel.rautou@inserm.fr

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

APHP-Beaujon Service Hepatologie, Hopital Beaujon groupe hospitalier HUPNVS APHP
Inserm Transfert Inserm Transfert
PARCC Paris-Cardiovascular research Center, team 1: Microparticles : Bioactive Markers in Atheroscerosis

Help of the ANR 215,448 euros
Beginning and duration of the scientific project: February 2013 - 24 Months

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