The Effect of Bariatric Surgery on Hepatic Metabolism in Non-Alcoholic Fatty Liver Disease

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to investigate the mechanisms underlying bariatric surgery-induced resolution of non-alcoholic fatty liver disease.

Detailed Description
-----------------
Bariatric surgery is one of the few currently available treatment options for non-alcoholic fatty liver disease (NAFLD). In most cases, NAFLD is entirely ameliorated after the surgery but in some individuals, the disease may persist or even progress. The mechanisms underlying the bariatric surgery-mediated resolution of NAFLD and the heterogeneity in the response remain poorly understood. In this study, the investigators will examine the metabolic effects of bariatric surgery-induced resolution of NAFLD. To this end, study subjects who have previously undergone bariatric surgery and metabolic studies will be invited for a follow-up visit for physical examination, evaluation of body composition with bioelectrical impedance and quantification of liver stiffness using non-invasive transient elastography and magnetic resonance elastography (MRE). Body fat composition will be evaluated by magnetic resonance imaging (MRI) and hepatic lipid content will be measured with magnetic resonance spectroscopy (MRS). In addition, 1H nuclear magnetic resonance (NMR) metabolomic analyses will be carried out from plasma samples collected both before and after bariatric surgery. Insulin resistance will be assessed using the HOMA-IR index and the genotypes in disease-modifying genes including PNPLA3, TM6SF2, MBOAT7, MARC1 and HSD17B13 will be assessed. Liver biopsies were obtained at the time of bariatric surgery and, in individuals with a clinical indication, a follow-up liver biopsy will be obtained.

Official Title
-----------------
The Effect of Bariatric Surgery on Hepatic Metabolism in Non-Alcoholic Fatty Liver Disease

Conditions
-----------------
Non-Alcoholic Fatty Liver Disease

Intervention / Treatment
-----------------
* Procedure: bariatric surgery


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participants must have undergone bariatric surgery and previously participated in a metabolic study in our research group. Participants must be able to communicate meaningfully with the investigator and must be legally competent to provide written informed consent. Age range from 18-75 years. Exclusion Criteria: No claustrophobia or metal implants to allow magnetic resonance spectroscopy. No pregnancy or lactation in women.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bariatric surgery<br> | Procedure: bariatric surgery<br>* bariatric surgery<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in concentration of plasma metabolites as determined by nuclear magnetic resonance | plasma NMR metabolomics concentrations (mmol/L) | change between follow-up visit and pre-surgery visit , expected average 10 years | 
| change in severity of NAFLD as determined by elastography | elastography (kPa) | change between follow-up visit and pre-surgery visit , expected average 10 years | 
| change in severity of NAFLD as determined by magnetic resonance spectroscopy | intrahepatic triglyceride content by proton magnetic resonance spectroscopy (%) | change between follow-up visit and pre-surgery visit , expected average 10 years | 
| change in severity of NAFLD as determined by liver histology | liver biopsy from individuals with clinical indication (SAF score) | change between follow-up visit and pre-surgery visit , expected average 10 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Fatty Liver, Liver Diseases, Digestive System Diseases, Bariatric Surgery