Alcohol Challenge On Liver and Gut Measured by Liver Vein Catheterization. A Pathophysiological Intervention Trial

Study Overview
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Brief Summary
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To investigate the effects of acute alcohol challenge on the gut and liver axis.

Detailed Description
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To study the role of acute alcohol challenge on the intestine permeability and inflow of bacterial products to the liver in participants with alcoholic liver disease, non-alcoholic steatohepatitis and healthy controls.

Conditions
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Liver Fibroses, Alcohol-Induced Disorders

Intervention / Treatment
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* Other: Ethanol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Alcoholic liver fibrosis, non-alcoholic steatohepatitis or liver-healthy individuals And all of following: Bodymass > 50 kg Able to be fasting and abstinent on the day of intervention international ratio <1.5 and platelets >100 x 10^9, 7 days before the intervention day Informed consent Exclusion Criteria: Antibiotics during the last 4 weeks Total alcohol abstinence Desire of total alcohol abstinence Other causes of liver disease suspected (viral, autoimmune, haemochromatosis, Wilsons diseases, alfa 1 antitrypsin deficiency or drug induced) Cirrhosis Insulin dependent diabetes mellitus Incapable to follow the protocol instructions Pregnancy Primary or secondary liver cancer Severe comorbidity Allergic to the contrast media iohexol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Alcoholic liver fibrosis<br> | Other: Ethanol<br>* 1 milliliter per kilogram body weight adjusted for elevated body mass index<br>|
| Active Comparator: Non-alcoholic steatohepatitis<br> | Other: Ethanol<br>* 1 milliliter per kilogram body weight adjusted for elevated body mass index<br>|
| Active Comparator: Healthy control<br> | Other: Ethanol<br>* 1 milliliter per kilogram body weight adjusted for elevated body mass index<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| changes in concentrations of bacterial products in the liver vein |  | Within 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| changes in concentrations of bacterial products in the peripheral vein system |  | Within 24 hours | 
| changes in the gut microbiome |  | Within 24 hours | 
| changes in the liver metabolome, transcriptome and proteome |  | Within 24 hours | 
| changes in serum-ethanol, plasma-glucose and liver biomarkers in the liver vein compared to the peripheral vein system |  | Within 24 hours |