Portal Hypertension and Systemic Endothelial Function

Portal Hypertension and Systemic Endothelial Function: Investigation of Systemic Endothelial Dysfunction in Case of Portal Hypertension Associated With Cystic Fibrosis.

Cystic fibrosis can affect organs other than the lungs. Liver disease affects about 30% of patients: its main manifestation is the development of portal hypertension (PHT). The pathophysiology of this comorbidity is still poorly understood. It was previously considered secondary to the formation of biliary cirrhosis but another hypothesis would be that of a primitive pathology of venous vessels may cause the gradual emergence of portal hypertension without cirrhosis. Evidence indiscutly suggest that cystic fibrosis is associated with a specific endothelial dysfunction, especially as the CFTR (Cystic Fibrosis Transmembrane conductance Regulator) protein is expressed on the surface of endothelial cells. The investigators hypothesize that liver disease related to PHT-associated cystic fibrosis is associated with systemic endothelial dysfunction.

The aim is:

To demonstrate a systemic endothelial dysfunction in patients with cystic fibrosis when associated with PHT.

To study the correlations between measures of systemic endothelial function and serum markers of endothelial dysfunction and between measures of liver stiffness and systemic endothelial function.

Prospective , monocentric study, with four groups of patients:

• Patients with cystic fibrosis and PHT
• Cystic fibrosis patients without PHT
• Patients free from cystic fibrosis with PHT from other causes
• Healthy controls. One study visit, no follow-up.

During the visit the following examinations will be performed:

• Collection of a blood sample of 21 mL.
• Liver eElastography achieved through hardware FibroScan® -
• Measurement of endothelial function with Endopat®
• Contrast-enhanced tomography. Abdominal CT scan will not be performed in healthy volunteers.

Inclusion Criteria:

• Patients over 18 years.
• Patients affiliated to a social security scheme
• Patients who have given their written consent
• Four study groups:
• Group A: Patients with cystic fibrosis (CF) with liver damage and diagnosis of CF is based on sweat test and genetic analysis). PHT diagnosis is based on tomographic criteria portal vein width superior to> 15 mm, portosystemic shunt and / or splenomegaly
• Group B: cystic fibrosis patients without PHT diagnosis is based on sweat test and genetic analysis). Absence of PHTP is predicated on tomographic of Scanner.
• Group C: Patients free of CF with PHT related to another cause. Patients followed for viral liver disease (hepatitis B or C) or idiopathic portal venous system disorder, with or without cirrhosis. The diagnosis of PHT is based on tomographic criteria portal vein width superior to> 15 mm, highlighting porto-systemic shunt, splenomegaly) and / or indirect signs namely ascitis or esophageal varices.
• Group D: Healthy controls.

Exclusion Criteria:

• Patients suffering from uncontrolled hypertension despite treatment (systolic BP> 160 mmHg);
• Patient with uncontrolled diabetes (glycated Hb measurement done during the last 3 months > 7%);
• Patients with uncorrected dyslipidemia;
• Patient suffering from a sleep apnea syndrome;
• Patients with severe coagulation disorders: PR< 50%, platelets < 30,000 / microL, current anticoagulant treatment;
• Patient with contra-indication to the injection of iodinated contrast material, including history of hypersensitivity to iodinated contrast media or renal clearance failure <50 ml / min Modification of Diet in Renal Disease (MDRD) formula
• Patients allergic to latex which contra-indicates endothelial function measurement;
• Acute pathology unresolved at the time of inclusion: respiratory exacerbation, ongoing infection, recent thrombosis;
• Smoking history> 10 pack-years;
• Vasoactive therapy that may interfere with the measurement of endothelial function and cannot be stopped 24 hours before the measurement: nitrates, beta-blockers, angiotensin converting enzyme inhibitors, calcium channel blockers, inhibitors of endothelin receptors, similar prostacyclin analog, inhibitors of phosphodiesterases;
• Pregnant and lactating women (all patients with childbearing potential will only be included if their β-human chorionic gonadotropin (β-HCG) urine test is negative;
• Patient unable to provide written consent. Patient under guardianship.