Clinical trial NCT04442334: The European NAFLD Registry
Official title: The European NAFLD Registry
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: NAFLD
NASH
NASH - Nonalcoholic Steatohepatitis
Fibrosis, Liver
Steatosis of Liver
Hepatocellular Carcinoma
Cardiovascular Diseases
Type 2 Diabetes
Dyslipidaemia
Hypertension
Obesity
Other Associated Comorbidities
Keywords: NAFLD
NASH
Steatohepatitis
Liver
Cirrhosis
Non-alcoholic fatty liver disease
Lead sponsor: Newcastle University
Sponsor class: OTHER
Collaborators: name: Newcastle-upon-Tyne Hospitals NHS Trust
name: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Institute of Cardiometabolism and Nutrition, France
name: University of Cambridge
name: Örebro University, Sweden
name: University of Bern
name: University of Oxford
name: University of Turin, Italy
name: University of Angers
name: University Hospital, Antwerp
name: Linkoeping University
name: University of Helsinki
name: UMC Utrecht
name: National and Kapodistrian University of Athens
name: University of Lisbon
name: University of Milan
name: University of Palermo
name: Catholic University of the Sacred Heart
name: Wuerzburg University Hospital
name: RWTH Aachen University
name: University of Nottingham
name: Medical University of Vienna
name: University of Birmingham
name: University of Florence
name: Assistance Publique - Hôpitaux de Paris
name: University Medical Center Mainz
First posted: 2020-06-22
Enrollment: 10000
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult patients with a pre-existing liver biopsy providing histological evidence of NAFLD or, patients undergoing liver biopsy for suspected NAFLD with biochemical and/or radiological findings consistent with NAFLD, or patients with radiological evidence of cirrhosis (in absence of an alternative aetiology) plus presence of ≥2 features indicative of the 'metabolic syndrome'.

Brief summary: 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.

Detailed 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.

Eligibility 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.

Primary outcomes:
measure: Detailed Characterisation of the NAFLD Patient Phenotype
timeFrame: 1 day
Secondary outcomes:
measure: Disease Natural History
timeFrame: Through to study completion, an average of 5 years
measure: Lifestyle factors: Dietary Habits
timeFrame: Through study completion, an average of 5 years
measure: Lifestyle factors: Activity/Exercise
timeFrame: Through study completion, an average of 5 years
measure: Health Related Quality of Life: CLDQ
timeFrame: Through study completion, an average of 5 years
measure: Health Related Quality of Life: EQ5D5L
timeFrame: Through study completion, an average of 5 years
measure: Health Related Quality of Life: NASH-CHECK
timeFrame: Through study completion, an average of 5 years
Other outcomes:
Locations:
city: Antwerp
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Helsinki
country: Finland
facility: Helsinki University Hospital
city: Angers
country: France
facility: Le Centre de Recherche Clinique (CRC) du CHU d'Angers
city: Paris
country: France
facility: Institut ICAN - Institute of Cardiometabolism And Nutrition Hôpital de la Pitié Salpêtrière
city: Aachen
country: Germany
facility: UNIVERSITÄTSKLINIKUM der RWTH Aachen
city: Berlin
country: Germany
facility: Charité University Hospital Berlin
city: Freiburg
country: Germany
facility: Universitätsklinikum Freiburg
city: Mainz
country: Germany
facility: UNIVERSITÄTSMEDIZIN der Johannes Gutenberg Universität Mainz
city: Würzburg
country: Germany
facility: Universitätsklinikums Würzburg
city: Athens
country: Greece
facility: Laiko General Hospital of Athens
city: Ancona
country: Italy
facility: Polytechnic University of Marche
city: Milan
country: Italy
facility: Università degli Studi Milano
city: Palermo
country: Italy
facility: Università di Palermo
city: Rome
country: Italy
facility: Università Cattolica del Sacro Cuore
city: Turin
country: Italy
facility: Department of Medical Sciences University of Torino
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC
city: Lisboa
country: Portugal
facility: Hospital de Santa Maria
city: Barcelona
country: Spain
facility: Vall d'Hebron University Hospital
city: Donostia
country: Spain
facility: Biodonostia Health Research Institute
city: Majadahonda
country: Spain
facility: Puerta de Hierro University Hospital
city: Santander
country: Spain
facility: Marqués de Valdecilla University Hospital
city: Sevilla
country: Spain
facility: Institute of Biomedicine of Sevilla (IBiS), Virgen del Rocío University Hospital
city: Valladolid
country: Spain
facility: HU Clínico de Valladolid
city: Huddinge
country: Sweden
facility: Karolinska Universitetssjukhuset
city: Linköping
country: Sweden
facility: Linköping University Hospital
city: Bern
country: Switzerland
facility: Inselspital, University Hospital
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham Nhs Foundation Trust
city: Cambridge
country: United Kingdom
facility: Addenbrooke'S Hospital
city: Gateshead
country: United Kingdom
facility: Queen Elizabeth Hospital
city: Hull
country: United Kingdom
facility: Hull Royal Infirmary
city: London
country: United Kingdom
facility: Royal London Hospital, Barts Health NHS Trust
city: London
country: United Kingdom
facility: St George's University Hospitals
city: Newcastle-upon Tyne
country: United Kingdom
facility: The Newcastle Upon Tyne Hospitals Nhs Foundation Trust
city: Nottingham
country: United Kingdom
facility: Queen'S Medical Centre
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals Nhs Foundation Trust
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
city: Portsmouth
country: United Kingdom
facility: Queen Alexandra Hospital
Study officials:
affiliation: Newcastle University
name: Quentin M Anstee, MBBS, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: McGlinchey AJ, Govaere O, Geng D, Ratziu V, Allison M, Bousier J, Petta S, de Oliviera C, Bugianesi E, Schattenberg JM, Daly AK, Hyotylainen T, Anstee QM, Oresic M. Metabolic signatures across the full spectrum of non-alcoholic fatty liver disease. JHEP Rep. 2022 Mar 26;4(5):100477. doi: 10.1016/j.jhepr.2022.100477. eCollection 2022 May.