The European NAFLD Registry

January 5, 2023 updated by: Newcastle University

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.

Study Overview

Status

Recruiting

Conditions

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.

Study Type

Observational

Enrollment (Anticipated)

10000

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Quentin M Anstee, MBBS, PhD
Phone Number: +44(0)191 20 87012
Email: quentin.anstee@ncl.ac.uk

Study Contact Backup

Name: Kristy L Wonders, BA, MLitt
Phone Number: +44(0)191 2083959
Email: kristy.wonders@ncl.ac.uk

Study Locations

Belgium
- - Antwerp, Belgium
    - Recruiting
    - Universitair Ziekenhuis Antwerpen
    - Contact:
      
      Sven M Francque, MD, PhD
      
      Phone Number: +3238214572
      
      Email: Sven.Francque@uza.be
    - Principal Investigator:
      
      Sven M Francque, MD, PhD
Finland
- - Helsinki, Finland
    - Recruiting
    - Helsinki University Hospital
    - Contact:
      
      Hannele Yki-Järvinen, MD
      
      Email: Hannele.Yki-Jarvinen@helsinki.fi
    - Principal Investigator:
      
      Hannele Yki-Järvinen, MD
France
- - Angers, France, 49933
    - Recruiting
    - Le Centre de Recherche Clinique (CRC) du CHU d'Angers
    - Contact:
      
      Jerome Boursier, MD, PhD
      
      Email: JeBoursier@chu-angers.fr
    - Principal Investigator:
      
      Jerome Boursier, MD, PhD
  - Paris, France, 75013
    - Recruiting
    - Institut ICAN - Institute of Cardiometabolism And Nutrition Hôpital de la Pitié Salpêtrière
    - Contact:
      
      Vlad Ratzu, MD
      
      Email: vlad.ratziu@inserm.fr
    - Principal Investigator:
      
      Vlad Ratzu, MD
Germany
- - Aachen, Germany, 52074
    - Not yet recruiting
    - Universitatsklinikum der RWTH Aachen
    - Contact:
      
      Christian Trautwein, MD
      
      Email: ctrautwein@ukaachen.de
    - Principal Investigator:
      
      Christian Trautwein, MD
  - Berlin, Germany
    - Not yet recruiting
    - Charité University Hospital Berlin
    - Contact:
      
      Muenevver Demir, MD
      
      Email: muenevver.demir@charite.de
    - Principal Investigator:
      
      Muenevver Demir, MD
  - Freiburg, Germany, 79106
    - Not yet recruiting
    - Universitatsklinikum Freiburg
    - Contact:
      
      Rafael Kaeser, DrMed
      
      Phone Number: +49 761 270-35500
      
      Email: rafael.kaeser@uniklinik-freiburg-.de
    - Principal Investigator:
      
      Rafael Kaeser, DrMed
  - Mainz, Germany, 55131
    - Recruiting
    - Universitatsmedizin der Johannes Gutenberg Universitat Mainz
    - Contact:
      
      Jörn M Schattenberg, DrMed
      
      Phone Number: +49 (0) 6131 176074
      
      Email: joern.schattenberg@unimedizin-mainz.de
    - Principal Investigator:
      
      Jörn M Schattenberg, DrMed
  - Würzburg, Germany, D-97080
    - Recruiting
    - Universitätsklinikums Würzburg
    - Contact:
      
      Andreas Geier, MD
      
      Email: Geier_A2@ukw.de
    - Principal Investigator:
      
      Andreas Geier, MD
Greece
- - Athens, Greece, 11527
    - Recruiting
    - Laiko General Hospital of Athens
    - Contact:
      
      Gergios Papatheodoridis, MD, PhD
      
      Email: gepapath@med.uoa.gr
    - Principal Investigator:
      
      Gergios Papatheodoridis, MD, PhD
Italy
- - Ancona, Italy
    - Recruiting
    - Polytechnic University of Marche
    - Contact:
      
      Gianluca Svegliati-Baroni, MD
      
      Email: gsvegliati@gmail.com
    - Principal Investigator:
      
      Gianluca Svegliati-Baroni, MD
  - Milan, Italy
    - Recruiting
    - Università degli Studi Milano
    - Contact:
      
      Luca Valenti, MD
      
      Email: luca.valenti@unimi.it
    - Principal Investigator:
      
      Luca Valenti, MD
  - Palermo, Italy
    - Recruiting
    - Università di Palermo
    - Contact:
      
      Salvatore Petta, MD, PhD
      
      Email: petta.salvatore@unipa.it
    - Principal Investigator:
      
      Salvatore Petta, MD, PhD
  - Rome, Italy
    - Recruiting
    - Universita Cattolica del Sacro Cuore
    - Contact:
      
      Luca Miele, MD, PhD
      
      Email: luca.miele@policlinicogemelli.it
    - Principal Investigator:
      
      Luca Miele, MD, PhD
  - Turin, Italy
    - Recruiting
    - Department of Medical Sciences University of Torino
    - Contact:
      
      Elisabetta Bugianesi, MD, PhD
      
      Email: elisabetta.bugianesi@unito.it
    - Principal Investigator:
      
      Elisabetta Bugianesi, MD, PhD
Netherlands
- - Amsterdam, Netherlands
    - Recruiting
    - Amsterdam UMC
    - Principal Investigator:
      
      Ulrich Beuers, MD, PHD
    - Contact:
      
      A G Holleboom, MD, PhD
      
      Email: a.g.holleboom@amsterdamumc.nl
    - Principal Investigator:
      
      A G Holleboom, MD, PhD
Portugal
- - Lisboa, Portugal
    - Recruiting
    - Hospital de Santa Maria
    - Contact:
      
      Helena Cortez-Pinto, MD, PhD
      
      Email: hlcortezpinto@netcabo.pt
    - Principal Investigator:
      
      Helena Cortez-Pinto, MD, PhD
Spain
- - Barcelona, Spain
    - Recruiting
    - Vall d'Hebron University Hospital
    - Contact:
      
      Salva Augustin, MD
      
      Email: salva.augustin@gmail.com
    - Principal Investigator:
      
      Salva Augustin, MD
  - Donostia, Spain
    - Recruiting
    - Biodonostia Health Research Institute
    - Contact:
      
      Jesus Banales, PhD
      
      Email: Jesus.banales@biodonostia.org
    - Principal Investigator:
      
      Jesus Banales, PhD
  - Majadahonda, Spain
    - Recruiting
    - Puerta de Hierro University Hospital
    - Contact:
      
      Joseluis Calleja, MD
      
      Email: Joseluis.calleja@uam.es
    - Principal Investigator:
      
      Joseluis Calleja, MD
  - Santander, Spain
    - Recruiting
    - Marques De Valdecilla University Hospital
    - Contact:
      
      Javier Crespo, MD
      
      Email: Javiercrespo1991@gmail.com
  - Sevilla, Spain
    - Recruiting
    - Institute of Biomedicine of Sevilla (IBiS), Virgen del Rocío University Hospital
    - Contact:
      
      Manuel Romero-Gomez, MD
      
      Email: mromerogomez@us.es
    - Principal Investigator:
      
      Manuel Romero-Gomez, MD
  - Valladolid, Spain
    - Recruiting
    - HU Clínico de Valladolid
    - Contact:
      
      Rocío Aller de la Fuente, MD, PhD
      
      Email: rallerf@saludcastillayleon.es
    - Principal Investigator:
      
      Rocío Aller de la Fuente, MD, PhD
Sweden
- - Huddinge, Sweden
    - Recruiting
    - Karolinska Universitetssjukhuset
    - Contact:
      
      Hannes Hagstrom, MD
      
      Email: hannes.hagstrom@ki.se
    - Principal Investigator:
      
      Hannes Hagstrom, MD
  - Linköping, Sweden
    - Recruiting
    - Linköping University Hospital
    - Contact:
      
      Mattias Ekstedt, MD
      
      Email: mattias.ekstedt@liu.se
    - Principal Investigator:
      
      Mattias Ekstedt, MD
Switzerland
- - Bern, Switzerland
    - Recruiting
    - Inselspital, University Hospital
    - Contact:
      
      Jean-Francois Dufour, MD, PhD
      
      Email: Jean-Francois.Dufour@insel.ch
    - Principal Investigator:
      
      Jean-Francois Dufour, MD, PhD
United Kingdom
- - Birmingham, United Kingdom
    - Recruiting
    - University Hospitals Birmingham NHS Foundation Trust
    - Contact:
      
      Philip Newsome, MBChB, PhD
      
      Email: P.N.Newsome@bham.ac.uk
    - Principal Investigator:
      
      Philip Newsome, MBChB, PhD
  - Cambridge, United Kingdom
    - Recruiting
    - Addenbrooke's Hospital
    - Contact:
      
      Michael Allison, MBBS, PhD
      
      Email: michael.allison@addenbrookes.nhs.uk
    - Principal Investigator:
      
      Mike Allison, MBBS, PhD
  - Gateshead, United Kingdom
    - Not yet recruiting
    - Queen Elizabeth Hospital
    - Contact:
      
      Dina Mansour, MA, MBBS
      
      Email: dina.mansour@nhs.net
    - Principal Investigator:
      
      Dina Mansour, MA, MBBS
  - Hull, United Kingdom
    - Recruiting
    - Hull Royal Infirmary
    - Contact:
      
      Lynsey Corless, MBChB, PhD
      
      Email: lynsey.corless@hey.nhs.uk
    - Principal Investigator:
      
      Lynsey Corless, MBChB, PhD
  - London, United Kingdom
    - Recruiting
    - Royal London Hospital, Barts Health NHS Trust
    - Contact:
      
      William Alazawi, MBBC, PhD
      
      Email: w.alazawi@nhs.net
    - Principal Investigator:
      
      William Alazawi, MBBC, PhD
  - London, United Kingdom
    - Recruiting
    - St George's University Hospitals
    - Contact:
      
      Metin Devrim, MSc, MBBS
      
      Email: MetinDevrim.Yalcin@stgeorges.nhs.uk
    - Principal Investigator:
      
      Metin Devrim, MSc, MBBS
  - Newcastle-upon Tyne, United Kingdom, NE7 7DN
    - Recruiting
    - The Newcastle Upon Tyne Hospitals NHS Foundation Trust
    - Contact:
      
      Quentin M Anstee, MBBS, PhD
      
      Email: quentin.anstee@ncl.ac.uk
    - Principal Investigator:
      
      Quentin M Anstee, MBBS, PhD
  - Nottingham, United Kingdom
    - Recruiting
    - Queen's Medical Centre
    - Contact:
      
      Guru Aithal, MD, PhD
      
      Email: Guru.Aithal@nuh.nhs.uk
    - Principal Investigator:
      
      Guru Aithal, MD, PhD
  - Oxford, United Kingdom
    - Recruiting
    - Oxford University Hospitals NHS Foundation Trust
    - Contact:
      
      Jeremy Cobbold, MBBS MA PhD
      
      Email: Jeremy.Cobbold@ouh.nhs.uk
    - Principal Investigator:
      
      Jeremy Cobbold, MBBS MA PhD
  - Plymouth, United Kingdom
    - Recruiting
    - Derriford Hospital
    - Contact:
      
      David Sheridan, MBBS, PhD
      
      Email: david.sheridan2@nhs.net
    - Principal Investigator:
      
      David Sheridan, MBBS, PhD
  - Portsmouth, United Kingdom
    - Recruiting
    - Queen Alexandra Hospital
    - Contact:
      
      Joanna Dowman, MBChB, PhD
      
      Email: Joanna.Dowman@porthosp.nhs.uk
    - Principal Investigator:
      
      Joanna Dowman, MBChB, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 100 years (Adult, Older Adult)

Accepts Healthy Volunteers

Genders Eligible for Study

All

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'.

Description

Inclusion Criteria:

Age ≥18 years.
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).
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

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.
Patients not meeting inclusion criteria or judged by the investigator to be unsuitable for inclusion in the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Observational Models: Cohort
Time Perspectives: Prospective

Number of groups / cohorts

Cohorts and Interventions

Group / Cohort
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Detailed Characterisation of the NAFLD Patient Phenotype Time Frame: 1 day	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Natural History Time Frame: Through to study completion, an average of 5 years	Longitudinal follow-up of patients with NAFLD by annual review to characterise disease natural history and determine number of participants experiencing clinically significant events including the occurrence and timing of incident comorbidities and key target conditions of interest such as: Death (cause of death) Major Adverse Cardiovascular Events (MACE) Hepatic (e.g. diagnosis of cirrhosis, hepatic decompensation, hepatocellular carcinoma, transplantation) Other (diagnosis of extra-hepatic malignancy/emergency hospitalisation) Routine clinical data generated as part of standard care will be collected annually. Clinical parameters assessed for changes indicative of alteration in disease state during follow-up include: clinical biochemistry/haematology, liver histology, comorbidities, prescribed medication and imaging data. Biological samples to support translational research into disease pathophysiology and biomarker development/validation will also be collected.	Through to study completion, an average of 5 years
Lifestyle factors: Dietary Habits Time Frame: Through study completion, an average of 5 years	Cross-sectional and longitudinal study of dietary habits in patients with NAFLD using: Mediterranean Diet Score.	Through study completion, an average of 5 years
Lifestyle factors: Activity/Exercise Time Frame: Through study completion, an average of 5 years	Cross-sectional and longitudinal study of lifestyle factors (e.g. activity/sedentary behaviour/exercise levels) in patients with NAFLD using: International Physical Activity Questionnaire (IPAQ).	Through study completion, an average of 5 years
Health Related Quality of Life: CLDQ Time Frame: Through study completion, an average of 5 years	Cross-sectional and longitudinal collection of standardised data on HRQOL and symptom burden in patients with NAFLD using Patient Reported Outcome Measure (PROM): Chronic Liver Disease Questionnaire for NAFLD NASH (CLDQ NAFLD-NASH).	Through study completion, an average of 5 years
Health Related Quality of Life: EQ5D5L Time Frame: Through study completion, an average of 5 years	Cross-sectional and longitudinal collection of standardised data on HRQOL and symptom burden in patients with NAFLD using Patient Reported Outcome Measure (PROM): EQ-5D-5L Health	Through study completion, an average of 5 years
Health Related Quality of Life: NASH-CHECK Time Frame: Through study completion, an average of 5 years	Cross-sectional and longitudinal collection of standardised data on HRQOL and symptom burden in patients with NAFLD using Patient Reported Outcome Measure (PROM): NASH-CHECK.	Through study completion, an average of 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Newcastle University

Collaborators

Assistance Publique - Hôpitaux de Paris

Medical University of Vienna

University of Nottingham

University of Palermo

UMC Utrecht

Catholic University of the Sacred Heart

University of Oxford

Linkoeping University

RWTH Aachen University

University Hospital, Antwerp

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

University of Bern

University of Helsinki

National and Kapodistrian University of Athens

University of Turin, Italy

University of Cambridge

University of Birmingham

Newcastle-upon-Tyne Hospitals NHS Trust

University of Florence

Wuerzburg University Hospital

Örebro University, Sweden

University of Milan

University of Lisbon

University Medical Center Mainz

Institute of Cardiometabolism and Nutrition, France

University of Angers

Investigators

Principal Investigator: Quentin M Anstee, MBBS, PhD, Newcastle University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 1, 2015

Primary Completion (Anticipated)

December 31, 2030

Study Completion (Anticipated)

December 31, 2030

Study Registration Dates

First Submitted

May 12, 2020

First Submitted That Met QC Criteria

June 19, 2020

First Posted (Actual)

June 22, 2020

Study Record Updates

Last Update Posted (Estimate)

January 6, 2023

Last Update Submitted That Met QC Criteria

January 5, 2023

Last Verified

January 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

08759
634413 (Other Grant/Funding Number: EU H2020)
777377 (Other Grant/Funding Number: EU H2020 IMI2)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Studies a U.S. FDA-regulated device product

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.