Non-alcoholic Fatty Liver Disease, Non-alcoholic Steatohepatitis
Conditions
Keywords
non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, NAFLD, NASH
Brief summary
The spectrum of NAFLD as emerging epidemic ranges from steatosis to steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC). Disease progression is poorly understood and treatment options are limited. Fructose overconsumption has been associated with gut permeability and progression of NAFLD. To unravel the mechanisms of fructose-induced intestinal changes, volunteers will receive a 4-week fructose challenge prior to assessment of intestinal permeability/translocation using endomicroscopy, sugar probes, serum markers of intestinal damage, inflammation, iron/copper homeostasis and histological/molecular analysis of intestinal biopsies. Findings in volunteers will be compared with liver patients undergoing study procedures without fructose challenge. Translational in vitro experiments will explore cellular responses to fructose and endotoxin. This project should provide novel insights into dietary induced alterations of the gut integrity in progression of NAFLD to NASH.
Interventions
DIETARY_SUPPLEMENTHigh oral Fructose challenge (150g per day for 28 days)
Sponsors
State Government of Vienna, Austria (Medizinisch-Wissenschaftlicher Fonds des Bürgermeisters der Bundeshauptstadt Wien)
Medical University of Vienna
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy men and women from 18 to 85, no disease history, no intake of regular medication. 2. Patients with confirmed (at least one imaging positive) intrahepatic fat accumulation (NAFL), male and female 3. Patients with confirmed NASH (biopsy within 6 months prior to study), male and female 4. Diagnosed HCV, genotype 1, male and female Signed informed consent General
Exclusion criteria
(for all groups) 1. Pregnancy and lactation 2. Imprisoned persons 3. Inflammatory bowel conditions (celiac disease, Crohn's disease, ulcerative colitis) 4. Prior bariatric surgery 5. Alcoholic steatohepatitis and/or alcohol consumption \> 140 gramms per week (or \> 30g/day) 6. Other liver diseases (autoimmune, genetic, cholestatic, Wilson disease, Weber-Christian disease, partial lipodystrophy of the face sparing type, abetalipoproteinemia, and jejunal diverticulosis with bacterial overgrowth.) 7. Virus hepatitis (A, B, C) (except for group (4): defined as HCV, genotype 1) 8. Known allergic reaction to the drugs used (see material and methods) 9. Intake of drugs known to accumulate intrahepatic lipids (e.g. steroids/glucocorticoids, tamoxifen, amiodarone, perhexiline maleate, synthetic estrogens, antiretroviral agents, tetracycline, minocycline, certain pesticides, methotrexate) 10. Intake of drugs known to drive fibrosis/cirrhosis (e.g. azathioprine, oral contraceptive pills) 11. Inability or contraindications to perform study procedures 12. General and absolute endoscopy contraindications
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Gaps per 1000 intestinal epithelial cells assessed by confocal laser endomicroscopy | Time point 1 (day 1 - all study groups) | Gaps per 1000 intestinal cells will be assesed during gastroscopy by confocal laser endomicroscopy at time point 1 in all study groups and after the 4 week fructose challange in healthy volunteers only |
Countries
Austria
Outcome results
None listed