Gut Permeability and Bariatric-metabolic Surgery

Study Overview
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Brief Summary
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Increased intestinal permeability and dysbiosis have been causally associated with NAFLD and NASH progression. However, to date, there are no systematic studies, on the effect of bariatric-metabolic surgery on intestinal permeability and dysbiosis in the context of NAFLD development.

Detailed Description
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Morbid obesity is associated with non-alcoholic fatty liver disease (NAFLD) in 80-90% of patients, and non-alcoholic steatohepatitis (NASH) occurs in up to 60% of patients. If left untreated, the disease can progress to liver fibrosis, cirrhosis, or hepatocellular carcinoma. Weight loss of >10% of body weight is the most effective treatment for NAFLD, and bariatric metabolic surgery plays an effective role in achieving long-term weight loss. About 80% of patients achieve improvement or reversal of NAFLD after bariatric-metabolic surgery. However, clinical and histological progression of liver disease may occur in about 20% of patients, despite weight the loss. Increased intestinal permeability and dysbiosis have been causally associated with NAFLD and NASH progression. However, to date, there are no systematic studies, on intestinal permeability and dysbiosis after bariatric-metabolic surgery. Research questions To investigate the changes in intestinal permeability after bariatric-metabolic surgery. To investigate the differences in intestinal permeability at the time of surgery and 1 year after surgery between patients with liver fibrosis grades F≤1 and F≥2 (low-grade fibrosis vs advanced fibrosis). To investigate differences between patients with and without liver fibrosis progression using parameters for metabolic endotoxemia, intestinal permeability, and dysbiosis.

Official Title
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Intestinal Permeability in Patients With Liver Fibrosis and NASH Progression Undergoing Bariatric-metabolic Surgery

Conditions
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NASH - Nonalcoholic Steatohepatitis, Bariatric Surgery Candidate, Intestinal Permeability

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with morbid obesity undergoing bariatric metabolic surgery according to the IFSO criteria, Willingness to attend all follow-up visits Written consent Exclusion Criteria: other liver disease than NAFLD presence of IBD, acute pancreatitis, amyotrophic lateral sclerosis, pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intestinal Permeability improves with significant weight loss after bariatric metabolic surgery | At the time of surgery and 12 months after surgery a multisugar (lactulose-mannitol) test will be performed, stool and blood samples will be taken. During surgery small bowel biopsies and liver biopsies will be taken. For the 12 months visit noninvasive fibrosis markers will be calculated, transient elastography will be performed and compared to the results from the intestinal permeability assays. Analysis will be performed on anonymized data only. A list cross-linking the patient number to the name will be kept secure and is only available to the principal researcher. Written informed consent will be kept for 15 years. Missing data will not be imputed but reported upon in the results. | 12 months observation period | 
| Refractory fibrosis or fibrosis progression after bariatric surgery is associated with persistent intestinal permeability | At the time of surgery and 12 months after surgery a multisugar (lactulose-mannitol) test will be performed, stool and blood samples will be taken. During surgery small bowel biopsies and liver biopsies will be taken. For the 12 months visit noninvasive fibrosis markers will be calculated, transient elastography will be performed and compared to the results from the intestinal permeability assays. Analysis will be performed on anonymized data only. A list cross-linking the patient number to the name will be kept secure and is only available to the principal researcher. Written informed consent will be kept for 15 years. Missing data will not be imputed but reported upon in the results. | 12 months observation period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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liver fibrosis, NAFLD, One Anastomosis Gastric Bypass, Roux-en-Y Gastric Bypass, Gut-liver axis