European Paediatric Non-Alcoholic Fatty Liver Disease Registry (EU-PNAFLD) (EU-PNAFLD)

The European Paediatric Non-alcoholic Fatty Liver Disease Registry (EU-PNAFLD): a Prospective, Longitudinal Follow-up of Children With Non-alcoholic Fatty Liver Disease

The EU-PNAFLD (The European Paediatric NALFD Registry) will be a network composed of European centres involved in the care of children with NAFLD, and will include Hepatologists, Endocrinologists, and Scientists, supported by relevant international specialists. This collaboration will build on existing infrastructure (local databases and bio-repositories) and will align with the adult European NAFLD Registry ("EPoS", Elucidating Pathways of Steatohepatitis study) to allow long-term follow-up supported by translational studies. Through an international, well-characterised large-scale cohort, we hope to: facilitate multi-centre clinical trials; extend our understanding of the key disease mechanisms of NAFLD; and establish the natural history of paediatric NAFLD.

Study Overview

• Status: Recruiting
• Conditions: Non-Alcoholic Fatty Liver Disease; Non-alcoholic Steatohepatitis; Non-alcoholic Fatty Liver

• Study Type: Observational
• Enrollment (Anticipated): 2000

Contacts and Locations

• Study Contact: Name: Jake P Mann, MRCPCH; Phone Number: 0044124644; Email: jm2032@cam.ac.uk

Study Locations

• Netherlands
  • Maastricht, Netherlands
    • Active, not recruiting
    • Maastricht UMC
• United Kingdom
  • Birmingham, United Kingdom
    • Recruiting
    • Birmingham Children's Hospital
    • Contact: Indra van Mourik
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ
      • Recruiting
      • Addenbrooke's Hospital
      • Contact: Jake P Mann; Phone Number: 00447804124644; Email: jm2032@cam.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Children with NAFLD who have been diagnosed either invasively (i.e. using liver biopsy) or using some form of imaging (USS, MRI, CT, MRS) plus exclusion of secondary causes using an appropriate panel of bloods. This aims to facilitate recruitment from a representative population of children, not just those from specialist centres who have undergone biopsy.

'Secondary NAFLD' (i.e. drug-induced, post-transplant) are not eligible. Children with insulin resistance syndromes are not specifically excluded however this is not the primary focus of EU-PNAFLD and other condition-specific registries are in existence.

Description

Inclusion Criteria:

• Diagnosis made under 18 years of age.
• Diagnosis of NAFLD spectrum disease (simple steatosis (NAFL), steatosis with abnormal transaminases, NASH ± fibrosis or cirrhosis)

• Diagnosis established by:

  • Radiological evidence of hepatic steatosis (e.g. increased hepatic echogenicity on ultrasound), with
  • Exclusion of secondary causes (negative serological liver screen for HBV/HCV, caeruloplasmin >0.20g/L, no history of excess alcohol consumption, no evidence of iron overload, and no clinically significant alpha-1 antitrypsin (A1AT) phenotype (i.e. SZ, ZZ, SS), with or without
  • Histology (>5% steatosis and histology consistent with paediatric NAFLD)

Exclusion Criteria:

• Secondary fatty liver disease (e.g. glycogen storage diseases, Wilson disease, viral hepatitis, drug-related, autoimmune hepatitis, type 1 diabetes mellitus)
• Post-transplant fatty liver
• >20g/day ethanol intake

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Non-alcoholic fatty liver disease patients; Children (<18 years) with a diagnosis of NAFLD with radiological demonstration of increased liver fat and exclusion of other causes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival	All-cause survival	30-year follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiovascular morbidity	CAD, CVA, PAD	30-year follow-up
Liver morbidity	Decompensated liver disease, transplantation, HCC development	30-year follow-up
Asymptomatic progression of liver disease	Presence of advanced fibrosis (on biopsy or non-invasive imaging)	30-year follow-up

Collaborators and Investigators

• Sponsor: Cambridge University Hospitals NHS Foundation Trust
• Collaborators: The European Association for the Study of the Liver; Children's Liver Disease Foundation
• Investigators: Principal Investigator: David B Savage, University of Cambridge

Publications and helpful links

General Publications

• Mann JP, Vreugdenhil A, Socha P, Janczyk W, Baumann U, Rajwal S, Casswall T, Marcus C, van Mourik I, O'Rahilly S, Savage DB, Noble-Jamieson G, Lacaille F, Dabbas M, Dubern B, Kelly DA, Nobili V, Anstee QM. European paediatric non-alcoholic fatty liver disease registry (EU-PNAFLD): Design and rationale. Contemp Clin Trials. 2018 Dec;75:67-71. doi: 10.1016/j.cct.2018.11.003. Epub 2018 Nov 5.

Study record dates

Study Major Dates

• Study Start (Actual): November 14, 2017
• Primary Completion (Anticipated): November 1, 2047
• Study Completion (Anticipated): November 1, 2047

Study Registration Dates

• First Submitted: December 5, 2019
• First Submitted That Met QC Criteria: December 5, 2019
• First Posted (Actual): December 9, 2019

Study Record Updates

• Last Update Posted (Actual): March 4, 2022
• Last Update Submitted That Met QC Criteria: February 17, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Type 2 diabetes; Atherosclerosis; Cirrhosis; Hepatocellular carcinoma; Liver disease
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: A094204; 174534 (Integrated Research Application System)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: No IPD will be shared with researchers outside of the Registry

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No