Mapping of Metabolic Liver Functions in Patients With Non-alcoholic Fatty Liver Disease

Study Overview
=================
Brief Summary
-----------------
Background: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the western world and an important cause of morbidity and mortality including risk of cardiovascular disease. A ruling dogma is that a fatty liver is well-functioning. Recent studies imply the contrary but quantitative measurements of metabolic liver function have not been systematically investigated in NAFLD. Objectives: To study and quantify specific metabolic liver functions in varying degrees of NAFLD. Furthermore to map the coagulation system of patients with NAFLD. Methods: A human clinical study. Metabolic liver functions are studied by a series of functional tests (Galactose elimination capacity (GEC), Aminopyrine breath test (ABT), Indocyanine green plasma disappearance rate (ICG-PDR), Functional hepatic nitrogen clearance (FHNC)). Regional liver function evaluated by 2-[18F]fluoro-2-deoxy-D-galactose (FDGal) PET/CT is compared to fat infiltration assessed by Magnetic resonance imaging (MRI). Primary and secondary hemostasis, natural anti-coagulants and fibrinolysis are evaluated. Perspectives: To challenge the dogma, that hepatic metabolic function is not affected in NAFLD, improving the understanding of the relationship between the clinical degree of NAFLD, histology, metabolic functions, and imaging. Furthermore to disclose a proposed procoagulant imbalance in NAFLD.

Official Title
-----------------
Mapping of Metabolic Liver Functions in Patients With Non-alcoholic Fatty Liver Disease

Conditions
-----------------
Non-alcoholic Fatty Liver Disease

Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age ≥ 18 Hepatic steatosis found on ultrasound Clinical indication for liver biopsy (typically persistently elevated alanine transaminase (ALT) levels) Exclusion Criteria: Other liver pathology Alcohol consumption > 20g/day Chronic inflammatory disease, current infection or cancer Diabetes mellitus type I, II or HbA1c ≥ 48 mmol/mol (6.5 %) Prednisolone treatment within last 8 weeks Pregnancy within last 12 months Contraindication for MRI

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

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

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------
What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Metabolic Liver Function assessed by GEC |  | Baseline | 
| Metabolic Liver Function assessed by FHNC |  | Baseline | 
| Metabolic Liver Function assessed by ABT |  | Baseline | 
| Metabolic Liver Function assessed by ICG-PDR |  | Baseline | 
| Regional metabolic liver function evaluated by FDGal PET/CT | 100 megabecquerel FDGal is injected intravenously in the beginning of a 20 min PET recording and 3D images of regional metabolic liver function expressed in terms of hepatic metabolic clearance of FDGal is created. | Baseline | 
| Regional fat infiltration assessed by MRI |  | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary hemostasis |  | Baseline | 
| Secondary hemostasis |  | Baseline | 
| Natural anti-coagulants |  | Baseline | 
| Fibrinolysis |  | Baseline | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Blood Coagulation, Liver Function Tests