Assessment of Endothelial Function in Patients With Non Alcoholic Fatty Liver Disease and the Impact of Statin Treatment

Study Overview
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Brief Summary
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The aim of the current study is to evaluate the association of fatty liver severity and endothelial function in Non-Alcoholic Fatty Liver Disease (NAFLD) patients and to find the impact of statin treatment compared to usual care or life style modification on endothelial function, liver steatosis and fibrosis.

Detailed Description
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The study cohort will include 150 patients with fatty liver per ultrasound or histology. The patients will be divided randomly to one of three arms: follow up group, lifestyle modification group, and statins therapy (Atorvastatin 20mg/d for 6 months). at screening, after 6 months (end of treatment), and 12 months the patients will undergo: complete physical examination blood pressure measurement assessment of height and weight, body mass index and waist circumference blood samples for complete blood count, fasting plasma glucose, fasting plasma insulin, lipid profile, liver enzymes, albumin, bilirubin, Prothrombin time (PT INR), Hemoglobin A1c, ferritin, adiponectin, C-reactive protein, Tumor necrosis factor alpha, Lipoprotein-phospholipase A2, Apolipoproteins B100, A1, C3, C4, ceruloplasmin Liver elastography and sonographic liver fat quantification Brachial artery flow-mediated dilatation (FMD) measurement

Official Title
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Assessment of Endothelial Function in Patients With Non Alcoholic Fatty Liver Disease and the Impact of Statin Treatment

Conditions
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Non Alcoholic Fatty Liver Disease

Intervention / Treatment
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* Drug: atorvastatin
* Behavioral: lifestyle counseling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: subjects willing to comply with study requirements and have signed an informed consent form fatty liver per abdominal ultrasound or liver biopsy Exclusion Criteria: alcohol drinking >140g/week presence of hepatitis B or C or HIV known liver disease other than fatty liver usage of drugs known to cause liver steatosis subjects with known allergies or hypersensitivity to statins subjects with known cardiovascular/cerebrovascular disease subjects with known dyslipidemia requiring drug treatment subjects with diabetes mellitus history of drug or alcohol abuse refusal to sig the informed consent form

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Statin<br>statin therapy (atorvastatin 20 mg/d) for 6 months | Drug: atorvastatin<br>* atorvastatin 20 mg per day for 6 months<br>* Other names: Atorvastatin Teva, Lipitor, Litorva;|
| No Intervention: usual care<br>follow up group with no intervention | |
| Active Comparator: lifestyle counseling<br>lifestyle modification by dietician counseling and follow-up | Behavioral: lifestyle counseling<br>* lifestyle modification by dietician counseling and follow up<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in liver steatosis at 6 months | Impact of statin treatment(which will be given for 6 months) compared to no intervention or lifestyle modification on liver steatosis and fibrosis. Liver steatosis will be assessed by sonographic liver fat quantification (hepatorenal sonographic index. | baseline, 6 months and 12 months | 
| change from baseline in liver fibrosis at 6 months | Impact of statin treatment(which will be given for 6 months) compared to no intervention or lifestyle modification on liver fibrosis. Liver fibrosis will be assessed by Real-Time shear wave elastography. | baseline, 6 months and 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| endothelial function in Non-Alcoholic Fatty Liver Disease (NAFLD) patients | measurement of endothelial function in NAFLD patients and finding the correlation between the degree of endothelial dysfunction and the severity of fatty liver disease. Endothelial function will be assessed by brachial artery flow-mediated (FMD) measurement at diagnosis and after 6 and 12 months. The severity of fatty liver disease will be assessed by liver elastography and sonographic liver fat quantification | 12 months | 
| relationship between blood parameters and liver steatosis and fibrosis | levels of liver enzymes, liver synthetic function, blood lipids, insulin resistance, ferritin, adiponectin, C reactive protein, Tumor necrosis factor alpha and ceruloplasmin and their correlation with liver steatosis and fibrosis | 12 months | 
| relationship between blood parameters and endothelial function | levels of liver enzymes, liver synthetic function, blood lipids, insulin resistance, ferritin, adiponectin, C reactive protein, tumor necrosis factor alpha and ceruloplasmin and their correlation with endothelial function | at diagnosis and after 6 months and 12 months | 
| change from baseline in endothelial function at 6 months | Impact of statin treatment(which will be given for 6 months) compared to no intervention or lifestyle modification on endothelial function. Endothelial function will be assessed by flow mediated dilatation (FMD) of brachial artery. | at diagnosis 6 months and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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non alcoholic fatty liver disease, endothelial function, liver steatosis, liver fibrosis, statin treatment