THE FRENCH NATIONAL NAFLD COHORT (FRench pAtients With MEtabolic Steatosis)

Study Overview
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Brief Summary
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The main objective of this cohort study is to determine genetic, clinical biologic and metabolic factors associated with patient heterogeneity in regards to severity of NAFLD at diagnosis as well as during the clinical course. at diagnosis, with the aim to better characterize patients of different severity and improve our understanding of clinical and histological heterogeneity at diagnosis during the clinical course to better understand and predict disease progression in terms notably of fibrosis progression and progression to cirrhosis

Detailed Description
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Non-alcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome and is currently the most common cause of liver disease in many developed countries worldwide. The aim of the study is to improve the scientific knowledge on markers associated with disease severity and progression in NAFLD. The study is a multicentre French NAFLD cohort of well-characterized patients with biological samples covering the entire spectrum of NAFLD severity (steatosis, NASH, significant fibrosis, cirrhosis, hepatocellular carcinoma).

Official Title
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Identification of Clinical and Biological Factors Determining Disease Severity and Disease Progression in NAFLD: THE FRENCH NATIONAL NAFLD COHORT FRAMES (FRench pAtients With MEtabolic Steatosis)

Conditions
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NAFLD, NASH, NASH - Nonalcoholic Steatohepatitis, Fibrosis, Cirrhosis

Intervention / Treatment
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* Other: Biological specimens
* Other: Additional visit


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years Patients with a confirmed diagnosis of NAFLD Patients affiliated to French social security Written informed consent signed by the patient Exclusion Criteria: Refusal or inability (lack of capacity) to give informed consent. Average alcohol ingestion greater than 21/14 units/week (males/females) in the preceding 6 months or history of sustained excessive consumption of alcohol in past 5 years. History or presence of Type 1 diabetes mellitus. Presence of any other form of chronic liver disease except NAFLD Recent (within 12 months) or concomitant use of agents known to cause hepatic steatosis (long-term systemic corticosteroids [>10 days], amiodarone, methotrexate, tamoxifen, tetracycline, high dose oestrogens, valproic acid). Any contra-indication to liver biopsy. Recent (within 3 months) change in dose/regimen or introduction of Vitamin E (at a dose ≥400 IU/day), betaine, s-adenosyl methionine, ursodeoxycholic acid, silymarin or pentoxifylline. Non-French speaking/unable to access an interpreter. Patients judged by the investigator to be unsuitable for inclusion in the study (e.g. judged by the physician as unlikely to be compliant with the study protocol). Pregnant or breastfeeding women Patient under legal protection measure (tutorship or curatorship) and patient deprived of freedom

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: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Patients<br>Patients with histologically confirmed NAFLD | Other: Biological specimens<br>* Biological specimens are collected to better characterize patients of different severity and improve our understanding of clinical and histological heterogeneity at diagnosis : added for the research : blood, urine, stools collected for the research : liver tissue sample, if a liver biopsy is indicated for clinical reasons (standard of care)<br>Other: Additional visit<br>* Visits if possible during standard care, otherwise added by the research (If necessary the annual visit will be added by research for the collection of biological samples)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease severity | The disease severity defined by the fibrosis stage on liver biopsy according to the semi-quantitative histological classification of NASH CRN. | Change of the fibrosis stage from baseline to 10 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ballooning grade |  | At baseline | 
| Lobular inflammation | Composite scores of Lobular inflammation (Ballooning and Inflammation) | At baseline | 
| Steatohepatitis | Presence or Absence | At baseline | 
| Cirrhosis | Cirrhosis defined by either : stage 4 of histological classification of fibrosis on liver biopsy or liver stiffness >14 kPa by elastometry | Through study completion, an average of 10 years | 
| Obesity | Obesity defined by either : Increased waist circumference by ethnically adjusted criteria or BMI ≥25 | Change from baseline to 10 years | 
| Type 2 diabetes | Type 2 diabetes defined by Fasting glucose ≥100 mg/dL [5.6 mmol/L], HbA1c ≥48mmol/mol (6.5%) or previously diagnosed insulin resistance/type 2 diabetes mellitus (or on treatment). | Change from baseline to 10 years | 
| Dyslipidaemia | Dyslipidaemia defined by fasting TG level ≥150 mg/dL [1.7mmol/L]; or fasting HDL <40 mg/dL [1.03 mmol/L] in males and <50 mg/dL [1.29 mmol/L] in females; or on treatment); | Change from baseline to 10 years | 
| Cardiovascular disease | Cardiovascular disease defined by arterial hypertension (systolic BP ≥130 or diastolic BP ≥85 mmHg, or on antihypertensive treatment). | Change from baseline to 10 years | 
| Necroinflammation measured by the activities component of the SAF | Necroinflammation measured by the activities component of the SAF classification : ranges 0 to 4 SAF : steatosis, activity, fibrosis | Change from baseline to 10 years | 
| Necroinflammation measured by the NAS score | Necroinflammation measured by the NAS score : ranges from 0 to 8 NAS score : NAFLD Activity Score | Change from baseline to 10 years | 
| Fasting insulin |  | Change from baseline to 10 years | 
| Insulin sensitivity | HOMA - %s | Change from baseline to 10 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cohort