A Randomized Controlled Study Evaluating Bariatric Surgery as a Treatment for Severe NASH With Advanced Liver Fibrosis in Non-severe Obese Patients

Inclusion criteria

• Provide written informed consent and agree to comply to the study protocol prior to enrolment.
• BMI and Brunt Fibriosis score:

• For F3 fibrosis patients: 35>BMI≥ 30kg/m² ; Fibroscan ≥ 9kPa or FibrometreVM ≥0.526 predicting a F3 fibrosis score grade within 1 month before inclusion or F3 fibrosis score grade diagnosed by hepatic biopsy performed before inclusion.
• For F4 fibrosis patients: 50>BMI≥ 30kg/m² ; Fibroscan ≥ 15kPa predicting a F4 fibrosis score grade within 1 month before inclusion or F4 fibrosis score grade diagnosed by hepatic biopsy performed before inclusion.
• Fibroscan ≥ 9kPa or FibrometreVM ≥0.526 predicting a F3 or F4 fibrosis score grade within 1 month before inclusion Or F3 or F4 fibrosis score grade diagnosed by hepatic biopsy performed before inclusion.
• Patient should agree to have one liver biopsy during the screening period (before randomization, the randomization will be permitted after at least a second reading performed by pathologist of CHRU Lille to confirm the histological diagnosis of NASH with advanced fibrosis (F3-F4)) for the diagnosis purpose (if no histological biopsy within 1 month before inclusion is available) and one at the end of the treatment period for assessment of the treatment effects.
• For patients with cirrhosis, patients must fulfil all the following criteria: Platelets > 125 000, PT > 80 %, Albumin > 35 g/L, MELD score at inclusion < 9, CPT score < 6, No history of previous decompensation, No oesophageal varices (endoscopy), No vascular shunt, ASA score ≤ III, Alcohol consumption lower than 20g/day for women and 30g/day for men.
• For hypertensive patients, hypertension must be controlled by stable dose of anti-hypertensive medication for at least 2 months prior to screening (and the stable dose can be maintained throughout the study).
• Female participating in the study must be either of non-child bearing (surgically sterilized at 6 month prior to screening or postmenopausal) or using an efficient contraception: hormonal contraception (including patch, contraceptive ring etc) intra-uterine device or other mechanical contraception
• Patient agrees to come to the study visits within the protocol-specified delay

Exclusion criteria

• Previous history of bariatric surgery (except gastric ring removed for more than 3 years).
• Decompensated cirrhosis (MELD> 7 CPT score> 5, previous history of decompensation (encephalopathy, ascites, jaundice, varicose vein rupture)
• Hepatocellular carcinoma
• Platelets <125 000; TP <80%; bilirubin <20 mmol / l; albumin <35 g / L.
• Other liver disease: alcohol consumption exceeding 20 g / day for women and 30g / day in men, HBV, HCV, CBP, CSP, autoimmune hepatitis, hemochromatosis, Wilson's disease, alpha-1 antitrypsin.
• Being processed Cancer (chemotherapy, radiotherapy or hormone therapy)
• HIV positive patients
• Patients who had an acute cardiovascular episode, coronary Heart Disease (Angina pectoris, myocardial infarction, revascularization procedure), stroke or TIA (Transient Ischemic Attack) within the 6 months prior to screening Recent cardiovascular events (stroke, myocardial infarcts, etc…) in the past 6 months.
• Severe chronic respiratory disease.
• Severe chronic cardiac insufficiency (grade III and IV of NYHA classification).
• Pregnant or breastfeeding women.
• Simultaneous enrollment in another clinical trial.
• Drug abuse within the past year.
• Patient with contra-indication for bariatric surgery
• Gastic Banding, Biliopancreatic diversion and all the new bariatric surgery techniques are forbidden because the study design allow only the laparoscopic sleeve gastrectomy or laparoscopic Roux-en-Y gastric Bypaass.
• History of cancer, except:

• Patients considered in remission for at least 5 years after onset of treatment.
• Patients Treated and believed to be cured basal or squamous cell carcinoma of the skin or resected carcinoma of the cervix