A Pathophysiological Study of the Postprandial Human Liver (PLS)

Study Overview
=================
Brief Summary
-----------------
Fatty liver disease is a globally widespread disease The identification of valid biomarkers and targets for potential treatments requires in-depth knowledge about the pathophysiology of the postprandial liver. The study will consist of five work packages (WP) including blood tests and liver biopsies taken after fasting or ingestion of a standardized meal in: healthy controls (WP 1), patients with NAFLD (WP 2), and patients with cirrhosis (WP 3) ; before and after a standardised meal in healthy controls (WP 4), and before and after glucagon in healthy controls (WP5)

Official Title
-----------------
A Pathophysiological Study of the Postprandial Human Liver (PLS)

Conditions
-----------------
Cirrhosis, Fatty Liver

Intervention / Treatment
-----------------
* Dietary Supplement: Standardised meal or glucagon


Participation Criteria
=================
Eligibility Criteria
-----------------
Healthy participants (WP 1 , WP 4 , WP 5 ) Inclusion criteria: Healthy adults, 20 - 40 years old, non-smoker, BMI 20-25 kg/m2 , no chronical illnesses, no medication. Exclusion criteria: Blood donation within the past 3 months, acute illness within 2 weeks NAFLD ( WP 2) Inclusion criteria: Patients with clinical diagnosis of NAFL and indication for liver biopsy Exclusion criteria: Malignant disease, acute illness within the past 2 weeks. Cirrhosis (WP 3) Inclusion criteria: Patients with clinical diagnosis of cirrhosis and indication for liver biopsy. Exclusion criteria:Malignant disease, acute illness within the past 2 weeks.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Intervention/Treatment |
| --- |
|Dietary Supplement: Standardised meal or glucagon|Standardised meal (Nutridrink, Nutricia, 300 kcal, 18.4 g carbohydrates, 5.8 g fat, 12 g protein) or 1mg glucagon|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postprandial phosphoproteomic changes in liver tissue in healthy individuals | Phosphorproteomic changes will be performed using MS-based approach that allows identification of phosphorylations sites at proteins in the liver. The comparison will be done between 'fasted' and 'postprandial' samples | 60 minutes after the meal administered at the study day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postprandial phosphoproteomic changes in liver tissue between healthy participants and patients with cirrhosis or patients with NAFLD. | Phosphorproteomic changes will be performed using MS-based approach that allows identification of phosphorylations sites at proteins in the liver. The comparison will be done between 'fasted' and 'postprandial' samples | 60 minutes after the meal administered at the study day | 
| Postprandial proteomic, metabolomic and transcriptomic changes in liver tissue in healthy individuals and compared to patients with cirrhosis and patients with NAFLD | Proteomic, metabolomic and transcriptomic changes will be performed using MS-based approaches and Next generation sequencing that allows identification of proteins, metabolites, RNA-transcripts in the liver. The comparison will be done between 'fasted' and 'postprandial' samples | 60 minutes after the meal administered at the study day | 
| Postprandial proteomic, metabolomic and Peptidomic changes in blood obtained from liver vein and peripheral vein in healthy individuals and compared to patients with cirrhosis and patients with NAFLD | Proteomic, metabolomic and hormonal changes will be performed using MS-based approaches and ELISAs that allows identification and measurements of proteins, metabolites and hormones from the liver. The comparison will be done between 'fasted' and 'postprandial' samples | 120 minutes after the meal administered at the study day | 
| Effect of exogenous glucagon on changes in liver phosphoproteomics, proteomics, metabolomics, and transcriptomics in healthy individuals. | Proteomic, metabolomic and transcriptomic changes will be performed using MS-based approaches and Next generation sequencing that allows identification of proteins, metabolites, RNA-transcripts in the liver. The comparison will be done between 'fasted' and samples obtained after glucagon injection | 30 minutes after the meal administered at the study day | 
| Effect of exogenous glucagon on changes in phosphoproteomics, proteomics, metabolomics and peptidomic in blood obtained from liver vein and peripheral vein in healthy individuals | Proteomic, metabolomic and hormonal changes will be performed using MS-based approaches and ELISAs that allows identification and measurements of proteins, metabolites and hormones from the liver. The comparison will be done between 'fasted' and samples obtained after glucagon injection | 120 minutes after the meal administered at the study day |