Comparison of Non-invasive Measurement Methods of Hepatic Fibrosis in Cystic Fibrosis

The incidence of hepatobiliary disease in cystic fibrosis in the first 10 years of life is 2.5 to 1.8 / 100 patient-years, significantly decreasing during the second decade; generally 30-40% of children develop hepatic disease before 12 years. However, the hepatobiliary damage varies in its clinical and histological expression. The typical histological appearance of the liver is the focal biliary cirrhosis (or fibrosis) characterized by a heterogeneous distribution of portal fibrosis in the liver.

Complications of cirrhosis are responsible for 2.5% of deaths in patients with cystic fibrosis and represent the second cause of death after lung disease if we exclude deaths secondary to lung transplantation.

The diagnosis of hepatic disease at an early stage of development and the assessment of the progression of fibrosis are so difficult in the absence of sensitive and specific non-invasive diagnostic tests.

Non-invasive assessment of hepatic fibrosis is an important topic of study in recent years, because of the emergence of biological methods and quantitative elastography methods using ultrasound or Magnetic Resonance Imagery (MRI) and allowing quantification of the hepatic elasticity, which is assumed to be a reflection of fibrosis. The advantages of these methods are numerous:

• The assessment of wider hepatic parenchyma then hepatic biopsy, allowing overcome the sampling bias
• Painless and non-invasive methods for the patient
• Simple to make
• Do not require hospitalization and can be performed as outpatient
• Immediately known results
• Can be repeated as often as necessary during the patient's follow-up
• Lower cost, morbidity and mortality compared to hepatic biopsy. Several non-invasive methods of fibrosis diagnosis have been studied in adults primarily for viral diseases and helped to limit the indications of hepatic biopsy. However, no method is now validated for the early diagnosis of hepatic disease and monitoring of children with cystic fibrosis.

The main objective of the study is to assess the contribution of FibroTest, the ultrasound impulse elastography, Fibroscan (FS), the ultrasound elastography by ShearWave (SWE) and Magnetic Resonance Elastography (MRE ) in the diagnosis of hepatic fibrosis in cystic fibrosis.

The secondary objectives are following :

• To study the correlations between the fibrosis quantitative results obtained through the four techniques of measurement and the matches between the results of four techniques using the standards available at t0 and after a year (t1).
• Study the correlations between clinical, biological and ultrasound endpoints of hepatic disease and various non-invasive measurement methods of fibrosis.
• Evaluate the area under the ROC curve of the different tests and the diagnostic performance tests using analytical methods without gold standard by classifying the children into two groups: the presence of advanced fibrosis (stages F2 to F4 ) or not (F0 and F1 stages), contracting by a committee according to the results of any biopsy, clinical, laboratory and ultrasound endpoints independent on the tests.

Inclusion criteria

• Children with cystic fibrosis aged 6-18 years. The diagnosis of cystic fibrosis will be based on testing the abnormal sweat (> 60 mEq / L of chloride sweat) and / or on the presence of two pathogen mutations of CFTR.
• Written consent of parents or holders of parental rights.
• Affiliated or benefiting from a national social insurance

Exclusion criteria

• Presence of another disease associated with cystic fibrosis that may be responsible for a chronic hepatic disease such as deficiency of alpha-1antitrypsine ZZ genotype or chronic infection by virus B or C.
• Child grafted
• Actual febrile pulmonary infection that can change the value of Fibrotest
• Important peri-hepatic ascites preventing the elasticity measurements by Fibroscan®
• Severe respiratory insufficient preventing attainment of Magnetic Resonance Imagery