The European NAFLD Registry

Newcastle University

Status: Enrolling

Conditions: Steatosis of Liver; Fibrosis, Liver; Obesity; Cardiovascular Diseases; Type 2 Diabetes; NAFLD; NASH; Hypertension; Other Associated Comorbidities; Hepatocellular Carcinoma; NASH - Nonalcoholic Steatohepatitis; Dyslipidaemia

Study type: Observational

Funder types: Other

Identifiers

NCT04442334

634413 (Other Grant/Funding Number)

777377 (Other Grant/Funding Number)

08759

Details and patient eligibility

About

The European NAFLD Registry is a prospectively recruited, observational study supporting the study of the clinical phenotype, natural history, disease outcomes and pathophysiology of Non-Alcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis. The ultimate goals are to better understand the drivers of interpatient variation in disease pathophysiology and severity and to utilise this information to develop and validate biomarkers that, singly or in combination, enable detection and monitoring of disease progression and/or from NAFL through NASH to fibrosis and cirrhosis.

Full description

The European NAFLD Registry is a major international collaboration between clinical academics at leading universities across Europe, initially established with funding from the European Association for the Study of the Liver and through the EU FP7, H2020 and IMI2 schemes to the projects FLIP (Fatty Liver Inhibition of Progression), EPoS (Elucidating Pathways of Steatohepatitis) and LITMUS (Liver Investigation: Testing marker Utility in Steatohepatitis).

The Registry is a non-interventional, observational study collecting cross-sectional and longitudinal clinical data (including clinical biochemistry/haematology, liver histology, comorbidities, prescribed medication and imaging data) and linked biological samples (Blood [Serum, Plasma], Liver Tissue, Urine, Stool) from prospectively recruited patients with NAFLD. Its purpose is to support clinical and translational research into disease pathophysiology (through development of comprehensive genetic, epigenetic, transcriptomic, metabolomic, proteomic and metagenomic datasets) and biomarker development/validation. It supports collaborative discovery science and serves as the basis for a broad international project to discover and validate biomarkers for NAFLD and associated medical conditions (LITMUS). Out-with the current study, following separate ethical approval and after separate consent, patients who have agreed to join the European NAFLD Registry may also agree to participate in a number of nested sub-studies with bi-directional sharing of data. These include the LITMUS Imaging Study, which will acquire additional imaging data across a range of modalities including, amongst others, MR-PDFF and MR-Elastography. The Registry population comprises adult patients (aged ≥18 years) with risk factors for non-alcoholic fatty liver disease (NAFLD) prospectively recruited primarily in hepatology and diabetology clinics and/or bariatric surgery units at centres across Europe. After receiving informed consent, patients will be assigned a unique study identifier (which will be used to identify all data and samples collected) which will allow all information to be recorded in a link-anonymised form.

Enrollment: 10,000 estimated patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

1. Age ≥18 years.

2. Clinically suspected NAFLD based on any of:

   1. Patient with historical liver biopsy providing histological evidence of NAFLD or,

   2. Patient undergoing liver biopsy for suspected NAFLD with biochemical and/or radiological findings consistent with NAFLD or,

   3. Patient with radiological evidence of cirrhosis (in absence of an alternative aetiology) plus presence of ≥2 features indicative of the 'metabolic syndrome':

      • Increased waist circumference by ethnically adjusted criteria (e.g. Europid male/female ≥94cm/80cm) or overweight/obese (BMI ≥25);
      • Raised 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);
      • Dyslipidaemia (fasting TG level ≥150 mg/dL [1.7 mmol/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);
      • Hypertension (systolic BP ≥130 or diastolic BP ≥85 mmHg, or on treatment).

3. Average alcohol consumption less than 21/14 units/week (males/females) in preceding 6 months and no history of sustained excessive consumption of alcohol in past 5 years.

Exclusion Criteria

1. Refusal or inability (lack of capacity) to give informed consent.
2. Average alcohol ingestion greater than approximately 21/14 units/week (males/females) in 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-English speaking/unable to access an interpreter. Due to the nature of the study, English language or access to a relevant interpreter is a necessary criterion to ensure lifestyle (diet and exercise) and symptom data are collated.
9. Patients not meeting inclusion criteria or judged by the investigator to be unsuitable for inclusion in the study.

Trial design

10,000 participants in 3 patient groups

The LITMUS Study Cohort

Description:

Prospectively recruited NAFLD patients, recruited according to The European NAFLD Registry study protocol.

The LITMUS Metacohort

Description:

Collated data and biological samples on patients with histologically characterised NAFLD prospectively recruited at contributing academic centres across Europe.

EFPIA Clinical Trial Cohort

Description:

Collated data and biological samples on patients with histologically characterised NAFLD that have participated in phase 2 and phase 3 trials of IMPs for NAFLD.