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

Medical University of Vienna

Status: Completed

Conditions: Non-alcoholic Fatty Liver Disease; Non-alcoholic Steatohepatitis

Treatments: Dietary Supplement: High oral Fructose challenge (150g per day for 28 days)

Study type: Interventional

Funder types: Other

Identifiers

NCT01696487

Fru1.0

Details and patient eligibility

About

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.

Enrollment: 10 patients

Sex: All

Ages: 18 to 85 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Prevention

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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10 participants in 4 patient groups

Healthy Volunteers

Experimental group

Description:

Volunteers will be challenged with oral 150g Fructose per day for 28 days.

Treatment:

Dietary Supplement: High oral Fructose challenge (150g per day for 28 days)

NAFLD

No Intervention group

Description:

Patients with confirmed fatty liver (imaging positive) will be compared at baseline with other arms.

NASH

No Intervention group

Description:

Patients with confirmed non-alcoholic steatohepatitis (biopsy proven) will be compared at baseline with other arms.

Hepatitis C genotype 1 (HCV-GT1)

No Intervention group

Description:

Patients with confirmed hepatitis C genotype 1 will be compared at baseline with other arms and act as different liver disease control group