Clinical trial NCT04190849: European Paediatric Non-Alcoholic Fatty Liver Disease Registry (EU-PNAFLD)
Official title: The European Paediatric Non-alcoholic Fatty Liver Disease Registry (EU-PNAFLD): a Prospective, Longitudinal Follow-up of Children With Non-alcoholic Fatty Liver Disease
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Non-Alcoholic Fatty Liver Disease
Non-alcoholic Fatty Liver
Non-alcoholic Steatohepatitis
Keywords: Cirrhosis
Liver disease
Hepatocellular carcinoma
Type 2 diabetes
Atherosclerosis
Lead sponsor: Cambridge University Hospitals NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: The European Association for the Study of the Liver
name: Children's Liver Disease Foundation
First posted: 2019-12-09
Enrollment: 2000
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Survival
timeFrame: 30-year follow-up
Secondary outcomes:
measure: Cardiovascular morbidity
timeFrame: 30-year follow-up
measure: Liver morbidity
timeFrame: 30-year follow-up
measure: Asymptomatic progression of liver disease
timeFrame: 30-year follow-up
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht UMC
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
state: Cambridgeshire
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital
Study officials:
affiliation: University of Cambridge
name: David B Savage
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.