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ID
Source
Brief title
Health condition
gallstones, NAFLD, Liver disease
Sponsors and support
Intervention
Outcome measures
Primary outcome
1. Presence of NAFLD/NASH parameters in liver biopsy using histology (NASH-CRN / Steatosis Activity and Fibrosis Score Steatosis) and liver RNA sequencing.
Secondary outcome
1. Presence of bacterial DNA, histology and inflammatory genes (RNA seq) liver and abdominal adipose tissue depots as well as metabolites in plasma, feces and urine
2. Fecal and oral microbiota composition
3. Dietary, psychological and satiety lists and excreted metabolites
4. Clinical data (body weight, body composition), waist circumference and blood pressure
5. Genomic DNA (buffy coat)
Background summary
The current estimated global prevalence of non-alcoholic fatty liver disease (NAFLD) is 25 – 30% and is diagnosed in up to 80% of individuals with obesity and type 2 diabetes (T2D) 1,2. The rapidly growing prevalence of NAFLD and lack of effective treatment options to tackle this potentially debilitating disease, will further increase obesity-related burden on public health and economies.
In order to develop appropriate, non-invasive diagnostic methods and treatment options, it is critical to deeply investigate the complex pathophysiology of NAFLD. Genome-wide analysis of large cohorts (containing hundreds of patients to insure the robustness of results), is required to obtain insight in hepatic metabolism in NAFLD 3. A number of such genome-wide transcriptomic studies have indeed characterized alterations in hepatic gene expression in individuals with NAFLD and its more severe, progressive form non-alcoholic steatohepatitis (NASH) 4 5 6 7. Nevertheless, these studies have thus far not been able to define a predictive transcriptome signature for NAFLD. Multiple confounding factors such as differences in genetic origin, sex and unappreciated environmental factors, including the gut microbiota, might have contributed to this.
Our research question therefore is how omics data of several biological layers are different between men and women with and without NAFLD and to what extent these signatures contribute to NAFLD development.
To answer this question, we will establish liver transcriptomic, fecal metagenomic and plasma metabolomics profiles of otherwise healthy men and women. Therefore, we will set up a cross-sectional cohort and include non-obese, otherwise healthy individuals scheduled for cholecystectomy. Using state-of-the-art sequencing and systems biology approaches, we can integrate plasma/urinary metabolomics, liver and adipose transcriptomic and fecal metagenomics data to create a unique much needed signature of healthy individuals (men and women). This database will be integrated in our large cohort of obese men and women with and without NAFLD (BARIA study METC 2015_357).
Study objective
How omics data of several biological layers are different between men and women with and without NAFLD and to what extent these signatures contribute to NAFLD development.
Study design
all time points are at the day of surgery (cross-sectional).
Inclusion criteria
- 18-65 years of age
- BMI < 30 kg/m2
- Individual should be able to give informed consent
Exclusion criteria
- Type 2 diabetes mellitus
- Prior bariatric surgery
- Inflammatory bowel disease
- Primary lipid disorder
- Known genetic basis for insulin resistance or glucose intolerance
- Ethanol intake > 2 U/week
- Pregnancy, females who are breastfeeding
- Hepatitis B and/or C
- Liver cirrhosis
- Auto-immune hepatitis
- Wilson disease3/ alpha 1-antitripsine deficiency
- Hemochromatosis
Design
Recruitment
IPD sharing statement
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL8983 |
| Other | METC AMC : METC 2020_130 |