Trial Information

Non Invasive Measurements of Fibrosis, Inflammation and Steatohepatitis in Morbidly Obese Patients

Main objective :

The main objective of the study was to determine in patients with morbid obesity waiting for
bariatric surgery, the accuracy of non-invasive tests for diagnosis of severe steatosis and
/ or NASH.

The gold standard is liver biopsy with a morphometric study.

Non-invasive tests will be used:

- Serum tests: the FibroMax (which includes the NASH test, FibroTest and SteatoTest) and
FibroMeter.

- Radiological examinations: MRI and FibroScan / CAP

Secondary objectives :

The secondary objectives are:

1. to determine the accuracy of these non-invasive tests for the diagnosis of severe
steatosis alone, steatohepatitis (NASH or) and hepatic fibrosis

2. to determine the best combination of these tests to better evaluate the presence of
severe steatosis, NASH and a hepatic fibrosis.

3. to quantify MRI visceral and subcutaneous fat in morbidly obese patients

Research Design :

1. Judging Criteria

Primary endpoint 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). The gold standard is the result of histology on liver
biopsy, with a morphometric study. For each diagnostic test, a ROC curve is used to
determine the best compromise between sensitivity and specificity.

The histological diagnosis of severe steatosis is defined by the presence of hepatic
steatosis grade 3 or higher. The diagnosis of NASH is defined by the presence of
lobular inflammation with neutrophils and hepatocytes ballooning.

Secondary endpoints

- 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
from the surface of the subcutaneous fat and the amount of intrahepatic fat assessed by
the percentage loss of signal).

2. Methodology and expected number of patients in research

This is a prospective study evaluating the value of noninvasive tests for the diagnosis
of hepatic lesions in morbid obese patients. The MRI system "open" allows access to
obese patients. Three such systems are available in France and liver pathology is
supported only on the system of Louis Mourier.

The reference method is liver histology; tests studied are MRI abdominal Fibroscan /
CAP, and serum tests (FibroTest, FibroMeter, SteatoTest, NASH test).

The study will be conducted in 200 obese patients who will have a liver biopsy
performed during bariatric surgery:

- Tests for the detection of steatosis (fat quantification of intrahepatic MRI
measurement of steatosis by CAP, serum tests) and evaluating histological
steatosis (main objective)

- Tests for the detection of NASH (test serum) and histology

- Tests of fibrosis (serum tests; FibroScan) and histological data assessing
fibrosis.

The duration and extent of obesity (BMI) and biological data (HOMA-test) will be taken
into account.

3. Examinations required specifically for research

Liver biopsy is routinely performed intraoperatively in the routine monitoring of
patients for bariatric surgery, examinations specific to the research are:

- Serum tests

- FibroScan / CAP

- Abdominal MRI

Risk / risk absences The sting at blood sampling can cause the formation of a small
hematoma without gravity, which will subside spontaneously within a few days.

FibroScan ® / CAP presents no risk of side effects. Liver MRI shows no risk if the
cons-indications are respected. Wearing a stack (pacemaker) or any element that
contains the iron near the eyes or head are contra-indications as are a major risk
factor (risk of death, blindness). The presence of a heart valve or a stent (also
called metal prosthesis) is not an absolute contra-indication-and their compatibility
with MRI will be verified before completion of the examination, as is the case in
practice clinic ..

Liver biopsy, which is part of the examinations carried out in a systematic way without
any protocol adds no additional risk to the surgical

4. Study site

The study will be conducted at Louis Mourier, a reference center for the treatment of
obesity, which has an open system allowing access to obese.

5. Indications for bariatric surgery

Indications for bariatric surgery at Louis Mourier, a reference center for the treatment of
obesity, are consistent with the recommendations of the HAS in 2009, based on professional
consensus.

Surgery is indicated in patients with all of the following criteria:

1. BMI ≥ 40 or BMI ≥ 35 with comorbid

2. failure (s) prior (s) of the conventional treatment of obesity combined dietary,
physical activity and behavioral therapy

3. appraisal nutritionally: global, personal and non-surgical

4. considered only after medical treatment for a minimum of 1 year

5. well-informed and motivated patients, with acceptable surgical risks

6. obesity stable (or worsening) for five years

7. absence of endocrine pathology (adrenal, thyroid) may be due to obesity