Non Invasive Measurements of Fibrosis, Inflammation and Steatohepatitis in Morbidly Obese Patients (FIRM)
Fatty liver most frequently corresponds to a fat overload of the liver. It is usually classified as alcoholic steatosis or non-alcoholic steatosis. In the case of non alcoholic fatty liver overload, the histological spectrum ranges from simple steatosis to steatohepatitis (NASH) which associates inflammation to steatosis, with a risk of progression to fibrosis and cirrhosis. Obese patients are at particular risk of NASH. Screening of these hepatic lesions is difficult especially as they may exist while the liver tests are normal. The diagnosis of NASH is currently done by liver biopsy, which exposes them in particular to the risk of hemorrhagic complications.
The main objective of the study was to determine in patients with morbid obesity waiting for bariatric surgery, the accuracy of non-invasive tests to assess liver steatosis, fibrosis and inflammation for the diagnosis of NASH, taking as reference the liver biopsy with a morphometric study of these parameters.
Patients with the following criteria will be eligible for the study:
- Age ≥ 18 years
- BMI ≥ 35 kg/m2
- Bariatric surgery scheduled within 3 months following the inclusion
- Signature of informed consent
Patients with at least one of the following criteria will not be eligible for the study
- Patient non-affiliated to a social security scheme (beneficiary or assignee)
- Contra-indication for performing an MRI
- weight>230 kg; anteroposterior diameter>40 cm
- Cancer treatment or medication that may induce lesions of steatohepatitis (corticoids, methotrexate, amiodarone, perhexiline, tamoxifen, nifedipine, diltiazem, hycanthone)
- Alcohol consumption >20 g per day for women and >30 g per day for men AND no past history of excessive alcohol use for more than a 2-year period within the last 20 years
- Known chronic liver disease (except for steatosis): presence of HBs antigen, or antibody to HCV, or anti-nuclear antibodies, anti-mitochondria, anti-LKM1, anti-smooth muscle negative, or the presence of a hemochromatosis,
- Known HIV positive status
- Pregnant (known pregnancy) or lactating women
Number of subjects required:
According to the literature and data collected Louis Mourier in the recent years, the inclusion of 200 patients would examine 20-40 patients with severe histological steatosis and steatohepatitis. All patients will be included in Louis Mourier hospital.
Follow-up: one month Search duration: 37 months Duration inclusions: 36 months The total duration of participation for a patient will be one month.
It is a monocentric, prospective study evaluating the value of noninvasive tests for the diagnosis of hepatic lesions in morbid obese patients. The "open " MRI system allows access to MRI for all obese patients (maximum weight 250 kg). Three of such systems are available in France and liver pathology can be explored only on the system of Louis Mourier.
The reference method is liver histology; studied tests are abdominal MRI, Fibroscan / CAP, and serum tests.
Examinations required specifically for research Examinations required specifically for the research is abdominal MRI, FibroScan/ CAP and serum tests.
Primary endpoint :
To validate the use of abdominal MRI, the FibroScan/ CAP and serum tests for finding severe steatosis and / or NASH, specificity, sensitivity, positive and negative predictive values of these tests are calculated. The gold standard is the result of histology on liver biopsy, with a morphometric study of these parameters. ROC curves are used to determine the best compromise between sensitivity and specificity.
The secondary endpoints were:
Histological lesions of liver fibrosis. Quantification of abdominal fat by MRI (in the form of three variables of interest: quantification of the surface of the visceral fat, of subcutaneous fat and of intrahepatic fat assessed by the percentage loss of signal
Non Alcoholic Steatohepatitis
|Study Design:||Observational Model: Case-Only
Time Perspective: Prospective
|Official Title:||Non Invasive Measurements of Fibrosis, Inflammation and Steatohepatitis in Morbidly Obese Patients|
- To validate the use of serum tests, FibroScan / CAP abdominal MRI for the diagnosis of severe steatosis and / or NASH (specificity, sensitivity, positive and negative predictive values) [ Time Frame: 3 months ] [ Designated as safety issue: No ]serum tests, FibroScan/CAP abdominal MRI
- Histological lesions of liver fibrosis and quantification of abdominal fat by MRI [ Time Frame: 3 months ] [ Designated as safety issue: No ]quantification of abdominal fat by MRI in the form of three variables of interest: quantification of the surface of the visceral fat from the surface of the subcutaneous fat and the amount of intrahepatic fat assessed by the percentage loss of signal
Biospecimen Retention: Samples Without DNA
blood, liver biopsy
|Study Start Date:||October 2012|
|Estimated Study Completion Date:||June 2016|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
Please refer to this study by its ClinicalTrials.gov identifier: NCT01695083
|Contact: Pauline Jouët, MD||+33 (0)1 47 60 63 firstname.lastname@example.org|
|Hôpital Louis Mourier||Recruiting|
|Colombes, France, 92700|
|Contact: Pauline Jouët, MD +33 (0)1 47 60 63 93 email@example.com|
|Principal Investigator: Pauline Jouët, MD|
|Principal Investigator: Muriel Coupaye, MD|
|Principal Investigator: Elisabeth Dion, MD, PhD|
|Sub-Investigator: Séverine Ledoux, MD|
|Principal Investigator:||Pauline Jouët, MD||Assistance Publique - Hôpitaux de Paris|