Impact of Fructose Consumption on Intestinal Permeability in Non-alcoholic Fatty Liver Disease (NAFLD) - a Pilot Study.

Impact of Fructose Consumption on Intestinal Permeability in Non-alcoholic Fatty Liver Disease (NAFLD) - a Pilot Study.

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.

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