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

Not Applicable

Not yet recruiting

• Conditions: NASH - Nonalcoholic Steatohepatitis; Fibrosis; NAFLD; NASH; Cirrhosis
• Interventions: Other: Biological specimens; Other: Additional visit

• Registration Number: NCT04925362
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

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

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).

Study Timeline

• Study First Submitted: 2021-02-24
• Status Verified: 2021-05
• Study Start: 2021-06
• Study First Submitted QC: 2021-06-07
• Last Update Submitted: 2021-06-07
• Study First Posted: 2021-06-14
• Last Update Posted: 2021-06-14
• Primary Completion: 2036-06
• Study Completion: 2036-06

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 900

Inclusion Criteria

1. Age ≥18 years
2. Patients with a confirmed diagnosis of NAFLD
3. Patients affiliated to French social security
4. Written informed consent signed by the patient

Exclusion Criteria

1. Refusal or inability (lack of capacity) to give informed consent.
2. 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.
3. History or presence of Type 1 diabetes mellitus.
4. Presence of any other form of chronic liver disease except NAFLD
5. 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).
6. Any contra-indication to liver biopsy.
7. 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.
8. Non-French speaking/unable to access an interpreter.
9. 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).
10. Pregnant or breastfeeding women
11. Patient under legal protection measure (tutorship or curatorship) and patient deprived of freedom

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Patients	Biological specimens	Patients with histologically confirmed NAFLD
Patients	Additional visit	Patients with histologically confirmed NAFLD

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Ballooning grade	At baseline
Lobular inflammation	At baseline	Composite scores of Lobular inflammation (Ballooning and Inflammation)
Type 2 diabetes	Change from baseline to 10 years	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).
Fasting insulin	Change from baseline to 10 years
Insulin sensitivity	Change from baseline to 10 years	HOMA - %s
Steatohepatitis	At baseline	Presence or Absence
Obesity	Change from baseline to 10 years	Obesity defined by either : 1. Increased waist circumference by ethnically adjusted criteria or; 2. BMI ≥25
Cardiovascular disease	Change from baseline to 10 years	Cardiovascular disease defined by arterial hypertension (systolic BP ≥130 or diastolic BP ≥85 mmHg, or on antihypertensive treatment).
Necroinflammation measured by the activities component of the SAF	Change from baseline to 10 years	Necroinflammation measured by the activities component of the SAF classification : ranges 0 to 4; SAF : steatosis, activity, fibrosis
Dyslipidaemia	Change from baseline to 10 years	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);
Cirrhosis	Through study completion, an average of 10 years	Cirrhosis defined by either : 1. stage 4 of histological classification of fibrosis on liver biopsy or; 2. liver stiffness \>14 kPa by elastometry
Necroinflammation measured by the NAS score	Change from baseline to 10 years	Necroinflammation measured by the NAS score : ranges from 0 to 8; NAS score : NAFLD Activity Score