The European NAFLD Registry

NCT04442334 | Recruiting DMC

• 3 other identifiers: 08759634413777377
• Study Type: observational
• Target: 10,000
• Locations: 12 countries
• Sites: 37

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.

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

Outcome Measures

Primary Outcomes (1)

• Detailed Characterisation of the NAFLD Patient Phenotype

  Prospective patient recruitment and collection of cross-sectional clinical data is undertaken (including clinical biochemistry/haematology, liver histology, comorbidities, prescribed medication and imaging data).These data will be used to determine number of participants exhibiting specific features of NAFLD/NASH disease severity at enrolment including: histological grade of disease and fibrosis stage (assessed using the well validated NASH Clinical Research Network "NAFLD Activity Score" \[NAS\] and the FLIP "Steatosis - Activity - Fibrosis" \[SAF\] systems), frequency of common metabolic comorbidities (eg type 2 diabetes mellitus, dyslipidaemia, cardiovascular disease), and associated changes in clinical biochemistry/haematology/imaging parameters. Biological samples to support clinical and translational research into disease pathophysiology (e.g. genetic, epigenetic, transcriptomic, metabolomic, proteomic and metagenomic datasets) and biomarker development/validation will be collected.

  1 day

Secondary Outcomes (6)

• Disease Natural History

  Through to study completion, an average of 5 years

• Lifestyle factors: Dietary Habits

  Through study completion, an average of 5 years

• Lifestyle factors: Activity/Exercise

  Through study completion, an average of 5 years

• Health Related Quality of Life: CLDQ

  Through study completion, an average of 5 years

• Health Related Quality of Life: EQ5D5L

  Through study completion, an average of 5 years

Study Arms (3)

The LITMUS Study Cohort

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

The LITMUS Metacohort

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

EFPIA Clinical Trial Cohort

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.

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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'.

You may qualify if:

• Age ≥18 years.
• Clinically suspected NAFLD based on any of:
• Patient with historical liver biopsy providing histological evidence of NAFLD or,
• Patient undergoing liver biopsy for suspected NAFLD with biochemical and/or radiological findings consistent with NAFLD or,
• 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).
• 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.

You may not qualify if:

• Refusal or inability (lack of capacity) to give informed consent.
• 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.
• 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-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.

Sponsors & Collaborators

• Newcastle University: lead
• Newcastle-upon-Tyne Hospitals NHS Trust: collaborator
• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): collaborator
• Institute of Cardiometabolism and Nutrition, France: collaborator
• University of Cambridge: collaborator
• Örebro University, Sweden: collaborator
• University of Bern: collaborator
• University of Oxford: collaborator
• University of Turin, Italy: collaborator
• University of Angers: collaborator
• University Hospital, Antwerp: collaborator
• Linkoeping University: collaborator
• University of Helsinki: collaborator
• UMC Utrecht: collaborator
• National and Kapodistrian University of Athens: collaborator
• University of Lisbon: collaborator
• University of Milan: collaborator
• University of Palermo: collaborator
• Catholic University of the Sacred Heart: collaborator
• Wuerzburg University Hospital: collaborator
• RWTH Aachen University: collaborator
• University of Nottingham: collaborator
• Medical University of Vienna: collaborator
• University of Birmingham: collaborator
• University of Florence: collaborator
• Assistance Publique - Hôpitaux de Paris: collaborator
• University Medical Center Mainz: collaborator

Study Sites (37)

Universitair Ziekenhuis Antwerpen

Antwerp, Belgium

RECRUITING

Helsinki University Hospital

Helsinki, Finland

RECRUITING

Le Centre de Recherche Clinique (CRC) du CHU d'Angers

Angers, 49933, France

RECRUITING

Institut ICAN - Institute of Cardiometabolism And Nutrition Hôpital de la Pitié Salpêtrière

Paris, 75013, France

RECRUITING

UNIVERSITÄTSKLINIKUM der RWTH Aachen

Aachen, 52074, Germany

NOT YET RECRUITING

Charité University Hospital Berlin

Berlin, Germany

NOT YET RECRUITING

Universitätsklinikum Freiburg

Freiburg im Breisgau, 79106, Germany

NOT YET RECRUITING

UNIVERSITÄTSMEDIZIN der Johannes Gutenberg Universität Mainz

Mainz, 55131, Germany

RECRUITING

Universitätsklinikums Würzburg

Würzburg, D-97080, Germany

RECRUITING

Laiko General Hospital of Athens

Athens, 11527, Greece

RECRUITING

Polytechnic University of Marche

Ancona, Italy

RECRUITING

Università degli Studi Milano

Milan, Italy

RECRUITING

Università di Palermo

Palermo, Italy

RECRUITING

Università Cattolica del Sacro Cuore

Rome, Italy

RECRUITING

Department of Medical Sciences University of Torino

Turin, Italy

RECRUITING

Amsterdam UMC

Amsterdam, Netherlands

RECRUITING

Hospital de Santa Maria

Lisbon, Portugal

RECRUITING

Vall d'Hebron University Hospital

Barcelona, Spain

RECRUITING

Biodonostia Health Research Institute

Donostia / San Sebastian, Spain

RECRUITING

Puerta de Hierro University Hospital

Majadahonda, Spain

RECRUITING

Marqués de Valdecilla University Hospital

Santander, Spain

RECRUITING

Institute of Biomedicine of Sevilla (IBiS), Virgen del Rocío University Hospital

Seville, Spain

RECRUITING

HU Clínico de Valladolid

Valladolid, Spain

RECRUITING

Karolinska Universitetssjukhuset

Huddinge, Sweden

RECRUITING

Linköping University Hospital

Linköping, Sweden

RECRUITING

Inselspital, University Hospital

Bern, Switzerland

RECRUITING

University Hospitals Birmingham Nhs Foundation Trust

Birmingham, United Kingdom

RECRUITING

Addenbrooke'S Hospital

Cambridge, United Kingdom

RECRUITING

Queen Elizabeth Hospital

Gateshead, United Kingdom

NOT YET RECRUITING

Hull Royal Infirmary

Hull, United Kingdom

RECRUITING

Royal London Hospital, Barts Health NHS Trust

London, United Kingdom

RECRUITING

St George's University Hospitals

London, United Kingdom

RECRUITING

The Newcastle Upon Tyne Hospitals Nhs Foundation Trust

Newcastle upon Tyne, NE7 7DN, United Kingdom

RECRUITING

Queen'S Medical Centre

Nottingham, United Kingdom

RECRUITING

Oxford University Hospitals Nhs Foundation Trust

Oxford, United Kingdom

RECRUITING

Derriford Hospital

Plymouth, United Kingdom

RECRUITING

Queen Alexandra Hospital

Portsmouth, United Kingdom

RECRUITING

Related Publications (1)

• 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.

  PMID: 35434590 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Blood (serum, plasma, whole blood, DNA, RNA), Liver tissue, Urine, stool, DNA, RNA

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Liver Cirrhosis; Fatty Liver; Carcinoma, Hepatocellular; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Dyslipidemias; Hypertension; Obesity; Fibrosis

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Lipid Metabolism Disorders; Vascular Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms

Study Officials

• Quentin M Anstee, MBBS, PhD

  Newcastle University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Quentin M Anstee, MBBS, PhD

CONTACT

+44(0)191 20 87012; quentin.anstee@ncl.ac.uk

Kristy L Wonders, BA, MLitt

CONTACT

+44(0)191 2083959; kristy.wonders@ncl.ac.uk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 10 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 12, 2020
• First Posted: June 22, 2020
• Study Start: May 1, 2015
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): December 31, 2030
• Last Updated: January 6, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

GR (1); NL (1); FI (1); IT (5); PT (1); ES (6); SE (2); CH (1); GB (11); BE (1); DE (5); FR (2)