MICROparticles for predicting clinically Significant Portal hYpertension – MICRO-SPY

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.