Gut Permeability and Bariatric-metabolic Surgery

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

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.

Study Overview

• Status: Recruiting
• Conditions: Bariatric Surgery Candidate; NASH - Nonalcoholic Steatohepatitis; Intestinal Permeability

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 125

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Recruiting
    • Medical University of Vienna
    • Contact: Magdalena Mairinger, MD, PhD; Phone Number: 004314040056210; Email: magdalena.mairinger@meduniwien.ac.at
    • Contact: Paula Richwien, MD; Phone Number: 004314040056210; Email: paula.richwien@meduniwien.ac.at

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

In our patients about 80% have NAFLD, about 50-60% are diagnosed with NASH. Furthermore, we know from our obese patient cohort, that 26% are diagnosed with fibrosis grade 2 or higher. Only patients that are scheduled for weight loss surgery will be enrolled in the study.

Description

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

Study Plan

How is the study designed?

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Medical University of Vienna

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2021
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: January 10, 2022
• First Submitted That Met QC Criteria: February 16, 2022
• First Posted (Actual): February 25, 2022

Study Record Updates

• Last Update Posted (Actual): March 20, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: NAFLD; liver fibrosis; One Anastomosis Gastric Bypass; Gut-liver axis; Roux-en-Y Gastric Bypass
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: 2180/2020

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No