Comparison of Non-invasive Measurement Methods of Hepatic Fibrosis in Cystic Fibrosis (MUCO-FIBRO)

Comparative Study of Different Non-invasive Measurement Methods of Hepatic Fibrosis in Cystic Fibrosis

Non-invasive methods of the quantification of fibrosis may help to assess the development of fibrosis at a specific moment of the evolution of the disease, in the order to decide the initiation of treatment with ursodeoxycholic acid which may slow the progression to hepatic cirrhosis:

• FibroTest,
• The ultrasound impulse elastography, Fibroscan (FS)
• Ultrasound Elastography by ShearWave (SWE)
• Magnetic resonance elastography (MRE). The purpose of this study is to assess the contribution of these methods in the diagnosis of hepatic fibrosis during the evolution of the cystic fibrosis.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Other: Measure of hepatic elasticity

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Paris, France, 75015
    • Hopital Necker

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: MUCO-FIBRO; Measures of hepatic elasticity	Other: Measure of hepatic elasticity; Measure of hepatic elasticity by four non-invasive methods: Fibroscan, Fibrotest, SWE, MRE.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure of hepatic elasticity by Fibro Test	The value of hepatic elasticity measured by each of the tests performed on the same day in the same patient	Day 0
Measure of hepatic elasticity by the ultrasound impulse elastography, Fibroscan (FS)	The value of hepatic elasticity measured by each of the tests performed on the same day in the same patient.	Month 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure of hepatic elasticity by Ultrasound Elastography by ShearWave (SWE):	The existence of advanced hepatic fibrosis (stages F2 to F4) will be defined by the presence of clinical, and / or biological and / or ultrasound abnormalities, defining two groups of children (F + :children with advanced fibrosis, F-: children with little or no fibrosis	Day 0
Measure of hepatic elasticity by Magnetic resonance elastography (MRE):	The existence of advanced hepatic fibrosis (stages F2 to F4) will be defined by the presence of clinical, and / or biological and / or ultrasound abnormalities, defining two groups of children (F + :children with advanced fibrosis, F-: children with little or no fibrosis	Month 12

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Vaincre la Mucoviscidose
• Investigators: Principal Investigator: Dominique Debray, MD, PhD, 00 33 1 44 49 41 52

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2015
• Primary Completion (Actual): January 1, 2019
• Study Completion (Actual): January 24, 2019

Study Registration Dates

• First Submitted: November 6, 2014
• First Submitted That Met QC Criteria: January 15, 2015
• First Posted (Estimate): January 21, 2015

Study Record Updates

• Last Update Posted (Actual): October 21, 2019
• Last Update Submitted That Met QC Criteria: October 18, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Cystic fibrosis; hepatic fibrosis; hepatic cirrhosis; non-invasive methods of measurement; hepatic elasticity
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis
• Other Study ID Numbers: RCB-2013-A01579-36