BILACO Trial: Biliary Atresia - a Severe Complex Congenital Liver Disease

Cognitive Impairment Clinical Trial

— BILACO  

Official title:

BILACO Trial: Biliary Atresia - a Severe Complex Congenital Liver Disease With High Mortality, Compromised Neurological Development, Severe Malnutrition and Unknown Etiology

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05399745
• Other study ID #: H-19042934
• Status: Recruiting
• Start date: March 1, 2020
• Est. completion date: December 31, 2040

Study information

• Verified date: May 2022
• Source: Rigshospitalet, Denmark
• Contact: Vibeke Brix Christensen, MD, PhD, DMSc
• Phone: +4535458842
• Email: vibeke.brix.christensen[@]regionh.dk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Biliary atresia is the most severe form of cholestatic liver disease. The children have high morbidity and mortality and get devastating pruritus and fatigue, failure to thrive, progressive hepatic failure and impaired neurodevelopment. The etiology is mostly unknown. More than half need a new liver from a living or deceased donor during childhood. However, correct timing of the transplantation is extremely difficult because of lack of consensus based on clinical assessment tools. All though the incidence is low, the cost of this disease is tremendous from both a clinical and human perspective. So far, protocolized neurodevelopment tests, genetic profiling, precise malnutrition evaluation based on clinical appearance, biochemical markers and brain MRI-scans, body composition, immunological function, level of physical activity and optimal time of transplantation in cholestatic children are unknown. The aim is to determine risk factors for neurocognitive impairment in children suffering from severe cholestasis in order to determine optimal time for liver transplantation from a brain perspective. In a prospective study, the investigators will investigate risk factors related to brain-, heart-, gut- and immunological function in the Danish cohort. This cohort consists of 75 children aged 0-18 years. In addition, 30 aged and gender matched healthy and 20 tetra fallot children will serve as control groups. The children will undergo extensive and advanced liver function evaluation, genetic profiling, nutrition and immunological status, neuro-imaging and neurocognitive evaluation at time of diagnose, 2 years of age, pre-school, pre-teenage, and teenage. In case of a liver transplantation, additional neuro-cognitive tests will be performed

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 31, 2040
• Est. primary completion date: December 31, 2039
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A to 18 Years

Eligibility

Inclusion Criteria:

• Biliary atresia
• Tetralogy of Fallot
• Healthy controls

Exclusion Criteria:

• Not able to participate in exams

Related Conditions & MeSH terms

• Biliary Atresia
• Cognitive Impairment
• Liver Diseases

Intervention

Other:
• Neurocognitive monitoring
Neurocognitive tests and MRI of the brain

Locations

Country	Name	City	State
Denmark	Rigshospitalet	Copenhagen

Sponsors (1)

Lead Sponsor	Collaborator
Rigshospitalet, Denmark

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	MRI of the brain	% of patients with anatomic anomalies on MRI of the brain	Inclusion
Primary	Neurocognitive status: Early movement repertoire (General movement)	Neurocognitive test panel depending on age at inclusion; % of patients with of abnormal movement assessed using early movement repertoire (GM) if inclusion at diagnosis. Early movement repertoire is a measurement tool where abnormal movement is identified.	Inclusion
Primary	Neurocognitive status: Alberta Infant Motor Scale	Neurocognitive test panel depending on age at inclusion: Alberta Infant Motor Scale if inclusion at diagnosis; Percentile, highest is the best	Inclusion
Primary	Neurocognitive status: Bayley Scales of Development III	Neurocognitive test panel depending on age at inclusion: Bayley Scales of Development III if inclusion up to 2.5 years: From 0-200, highest is best	Inclusion
Primary	Neurocognitive status: WIPPSI	Neurocognitive test panel depending on age at inclusion: WIPPSI if inclusion between 2.5-6 years: Wechsler Preschool and Primary Scale of Intelligence, from 41 to 160, highest is best	Inclusion
Primary	Neurocognitive status: ABC Movement	Neurocognitive test panel depending on age at inclusion: ABC Movement if inclusion between 2.5-16 years; Movement Assessment Battery for Children, mean 10 SD 3, highest is best	Inclusion
Primary	Neurocognitive status: WISC-IV	Neurocognitive test panel depending on age at inclusion: WISC-IV if inclusion between 6-16 years; Wechsler Intelligence Scale for Children, 40 to 160, highest is best	Inclusion
Primary	Neurocognitive status: Auditory Verbal Learning Test/ToMaL	Neurocognitive test panel depending on age at inclusion: Auditory Verbal Learning Test/ToMaL if inclusion between 6-18 years Mean 10 SD 3, highest is best	Inclusion
Primary	Neurocognitive status: TEA-Ch	Neurocognitive test panel depending on age at inclusion: TEA-Ch if inclusion between 6-18 years; Test of Everyday Attention for Children, normalized to z-score, highest is best	Inclusion
Primary	Neurocognitive status: BADS-C	Neurocognitive test panel depending on age at inclusion: BADS-C if inclusion between 6-18 years Behavioural Assessment of the Dysexecutive Syndrome in Children, 0-24, mean 10 SD 3, highest is best	Inclusion
Primary	Neurocognitive status: Test of Visual Perceptual Skills	Neurocognitive test panel depending on age at inclusion: Test of Visual Perceptual Skills if inclusion between 6-18 years; Percentile, highest is best	Inclusion
Primary	Neurocognitive status: CANTAB	Neurocognitive test panel depending on age at inclusion: CANTAB if inclusion between 6-18 years Cambridge Neuropsychological Test Automated Battery	Inclusion
Primary	Neurocognitive status: The Beery Visuo-Motor Integration test	Neurocognitive test panel depending on age at inclusion: The Beery Visuo-Motor Integration test if inclusion between 6-18 years Mean of 100 and standard deviation of 15, highest is best	Inclusion
Primary	Neurocognitive status: WAIS IV	Neurocognitive test panel depending on age at inclusion: WAIS IV if inclusion from 16 to 18 years Wechsler Adult Intelligence Scale, 40-160, highest is best	Inclusion
Primary	Neurocognitive status: Kiddie-sads	Neurocognitive test panel depending on age at inclusion: Kiddie-sads if included between 2-18 years Kiddie Schedule for Affective Disorders and Schizophrenia, 0-61, lowest is best	Inclusion
Primary	Neurocognitive status: BRIEF 1	Neurocognitive test panel depending on age at inclusion: BRIEF 1 if inclusion up to 6 years Behaviour Rating Inventory of Executive Function, percentile, lowest is best	Inclusion
Primary	Neurocognitive status: BRIEF 2	Neurocognitive test panel depending on age at inclusion: BRIEF 2 if inclusion between 6-18 years Behaviour Rating Inventory of Executive Function, percentile, lowest is best	Inclusion
Primary	Neurocognitive status: CBCL	Neurocognitive test panel depending on age at inclusion: CBCL if included between 2-18 years Child Behavior Checklist, percentile, lowest is best	Inclusion
Primary	Neurocognitive status: ADHD screening	Neurocognitive test panel depending on age at inclusion: ADHD screening if included between 2-18 years Lowest is best, 0-78	Inclusion
Primary	Neurocognitive status: SRS-2	Neurocognitive test panel depending on age at inclusion: SRS-2 screening if included between 6-18 years; Social Responsiveness Scale, 32-114. lowest is best	Inclusion
Primary	Neurocognitive status: Vineland	Neurocognitive test panel depending on age at inclusion: Vineland screening if included between 6-18 years Vineland Adaptive Behavior Scales, 20 to 160, highest is best	Inclusion
Primary	MRI of the brain	% of patients with anatomic anomalies on MRI of the brain	1 year
Primary	Neurocognitive status: Alberta Infant Motor Scale	Alberta Infant Motor Scale Percentile, highest is the best	1 year
Primary	Neurocognitive status: Bayley Scales of Development III	Bayley Scales of Development III; From 0-200, highest is best	1 year
Primary	Neurocognitive status: BRIEF 1	BRIEF 1 Behaviour Rating Inventory of Executive Function, percentile, lowest is best	1 year
Primary	Neurocognitive status: CBCL	CBCL Child Behavior Checklist, percentile, lowest is best	1 year
Primary	Neurocognitive status: Kiddie-Sads	Kiddie-Sads Kiddie Schedule for Affective Disorders and Schizophrenia, 0-61, lowest is best	1 year
Primary	MRI of the brain	% of patients with anatomic anomalies on MRI of the brain	2 years
Primary	Neurocognitive status: Bayley Scales of Development III	Bayley Scales of Development III From 0-200, highest is best	2 years
Primary	Neurocognitive status: BRIEF 1	BRIEF 1 Behaviour Rating Inventory of Executive Function, percentile, lowest is best	2 years
Primary	Neurocognitive status: CBCL	CBCL Child Behavior Checklist, percentile, lowest is best	2 years
Primary	Neurocognitive status: Kiddie-Sads	Kiddie-Sads Kiddie Schedule for Affective Disorders and Schizophrenia, 0-61, lowest is best	2 years
Primary	Neurocognitive status: ADHD	ADHD Lowest is best, 0-78	2 years
Primary	Neurocognitive status: Vineland	Vineland Adaptive Behavior Scales, 20 to 160, highest is best	2 years
Primary	MRI of the brain	% of patients with anatomic anomalies on MRI of the brain	6 years
Primary	Neurocognitive: Movement ABC	Neurocognitive test panel depending on age Movement Assessment Battery for Children, mean 10 SD 3, highest is best	6 years
Primary	Neurocognitive status: WISC-IV	WISC-IV; Wechsler Intelligence Scale for Children, 40 to 160, highest is best	6 years
Primary	Neurocognitive status: Auditory Verbal Learning Test/ToMaL	Auditory Verbal Learning Test/ToMaL Mean 10 SD 3, highest is best	6 years
Primary	Neurocognitive status: TEA-Ch	TEA-Ch Test of Everyday Attention for Children, normalized to z-score, highest is best	6 years
Primary	Neurocognitive status: BADS-C	BADS-C Behavioural Assessment of the Dysexecutive Syndrome in Children, 0-24, mean 10 SD 3, highest is best	6 years
Primary	Neurocognitive status: Test of Visual Perceptual Skills	Test of Visual Perceptual Skills Percentile, highest is best	6 years
Primary	Neurocognitive status: The Beery Visuo-Motor Integration test	The Beery Visuo-Motor Integration test Mean of 100 and standard deviation of 15, highest is best	6 years
Primary	Neurocognitive status: CANTAB	CANTAB Cambridge Neuropsychological Test Automated Battery	6 years
Primary	Neurocognitive status: BRIEF 2	BRIEF 2 Behaviour Rating Inventory of Executive Function, percentile, lowest is best	6 years
Primary	Neurocognitive status: ADHD screening	ADHD screening Lowest is best, 0-78	6 years
Primary	Neurocognitive status: SRS-2	SRS-2 Social Responsiveness Scale, 32-114. lowest is best	6 years
Primary	Neurocognitive status: Kiddie-Sads	Kiddie-Sads Kiddie Schedule for Affective Disorders and Schizophrenia, 0-61, lowest is best	6 years
Primary	Neurocognitive status: CBCL	CBCL Child Behavior Checklist, percentile, lowest is best	6 years
Primary	Neurocognitive status: Vineland	Vineland Vineland Adaptive Behavior Scales, 20 to 160, highest is best	6 years
Primary	MRI of the brain	% of patients with anatomic anomalies on MRI of the brain	11 years
Primary	Neurocognitive status: Movement ABC	Neurocognitive test panel depending on age at inclusion: ABC Movement if inclusion between 2.5-16 years; Movement Assessment Battery for Children, mean 10 SD 3, highest is best	11 years
Primary	Neurocognitive status: WISC-IV	WISC-IV; Wechsler Intelligence Scale for Children, 40 to 160, highest is best	11 years
Primary	Neurocognitive status: Auditory Verbal Learning Test/ToMaL	Auditory Verbal Learning Test/ToMaL Mean 10 SD 3, highest is best	11 years
Primary	Neurocognitive status:TEA-Ch	TEA-Ch Test of Everyday Attention for Children, normalized to z-score, highest is best	11 years
Primary	Neurocognitive status: BADS-C	BADS-C Behavioural Assessment of the Dysexecutive Syndrome in Children, 0-24, mean 10 SD 3, highest is best	11 years
Primary	Neurocognitive status: Test of Visual Perceptual Skills	Test of Visual Perceptual Skills Percentile, highest is best	11 years
Primary	Neurocognitive status: The Beery Visuo-Motor Integration test	The Beery Visuo-Motor Integration test Mean of 100 and standard deviation of 15, highest is best	11 years
Primary	Neurocognitive status: CANTAB	CANTAB Cambridge Neuropsychological Test Automated Battery	11 years
Primary	Neurocognitive status: BRIEF 2	BRIEF 2 Behaviour Rating Inventory of Executive Function, percentile, lowest is best	11 years
Primary	Neurocognitive status: ADHD screening	ADHD screening Lowest is best, 0-78	11 years
Primary	Neurocognitive status: SRS-2	SRS-2 Social Responsiveness Scale, 32-114. lowest is best	11 years
Primary	Neurocognitive status: Kiddie-Sads	Kiddie-Sads Kiddie Schedule for Affective Disorders and Schizophrenia, 0-61, lowest is best	11 years
Primary	Neurocognitive status: CBCL	CBCL Child Behavior Checklist, percentile, lowest is best	11 years
Primary	Neurocognitive status: Vineland	Vineland Adaptive Behavior Scales, 20 to 160, highest is best	11 years
Primary	MRI of the brain	% of patients with anatomic anomalies on MRI of the brain	16 years
Primary	Neurocognitive status: Movement ABC	Neurocognitive test panel depending on age at inclusion: ABC Movement if inclusion between 2.5-16 years; Movement Assessment Battery for Children, mean 10 SD 3, highest is best	16 years
Primary	Neurocognitive status: WISC-IV	WISC-IV Wechsler Adult Intelligence Scale, 40-160, highest is best	16 years
Primary	Neurocognitive status: Auditory Verbal Learning Test/ToMaL	Auditory Verbal Learning Test/ToMaL Mean 10 SD 3, highest is best	16 years
Primary	Neurocognitive status: TEA-Ch	TEA-Ch Test of Everyday Attention for Children, normalized to z-score, highest is best	16 years
Primary	Neurocognitive status: BADS-C	BADS-C Behavioural Assessment of the Dysexecutive Syndrome in Children, 0-24, mean 10 SD 3, highest is best	16 years
Primary	Neurocognitive status: Test of Visual Perceptual Skills	Test of Visual Perceptual Skills Percentile, highest is best	16 years
Primary	Neurocognitive status: The Beery Visuo-Motor Integration test	The Beery Visuo-Motor Integration test Mean of 100 and standard deviation of 15, highest is best	16 years
Primary	Neurocognitive status: CANTAB	CANTAB Cambridge Neuropsychological Test Automated Battery	16 years
Primary	Neurocognitive status: BRIEF 2	BRIEF 2 Behaviour Rating Inventory of Executive Function, percentile, lowest is best	16 years
Primary	Neurocognitive status: ADHD screening	ADHD screening Lowest is best, 0-78	16 years
Primary	Neurocognitive status: SRS-2	SRS-2 Social Responsiveness Scale, 32-114. lowest is best	16 years
Primary	Neurocognitive status: Kiddie-Sads	Kiddie-Sads Kiddie Schedule for Affective Disorders and Schizophrenia, 0-61, lowest is best	16 years
Primary	Neurocognitive status: CBCL	CBCL Child Behavior Checklist, percentile, lowest is best	16 years
Primary	Neurocognitive status: Vineland	Vineland Adaptive Behavior Scales, 20 to 160, highest is best	16 years
Secondary	Genetics: Whole genome sequencing of blood	Whole genome sequencing of blood	Inclusion
Secondary	Genetics: Whole genome sequencing of liver biopsy	Whole genome sequencing of liver biopsy	Inclusion
Secondary	Microbiome: Urine proteomics	Microbiome measurements on urine	Inclusion
Secondary	Microbiome: Feces proteomics	Microbiome measurements on feces	Inclusion
Secondary	Microbiome: Saliva proteomics	Microbiome measurements on saliva	Inclusion
Secondary	Microbiome: Feces Next Generation Sequencing of microbial DNA	Microbiome measurement on feces	Inclusion
Secondary	Microbiome: Urine Next Generation Sequencing of microbial DNA	Microbiome measurement on urine	Inclusion
Secondary	Microbiome: Saliva Next Generation Sequencing of microbial DNA	Microbiome measurement on saliva	Inclusion
Secondary	Microbiome: Feces metabolomics	Microbiome measurements on feces	Inclusion
Secondary	Microbiome: Urine metabolomics	Microbiome measurements on urine	Inclusion
Secondary	Microbiome: Saliva metabolomics	Microbiome measurements on saliva	Inclusion
Secondary	Microbiome: Feces metatranscriptomics	Microbiome measurements on feces	Inclusion
Secondary	Microbiome: Urine metatranscriptomics	Microbiome measurements on urine	Inclusion
Secondary	Microbiome: Saliva metatranscriptomics	Microbiome measurements on saliva	Inclusion
Secondary	Genetics: Whole genome sequencing of blood	Whole genome sequencing of blood	1 year
Secondary	Genetics: Whole genome sequencing of liver biopsy	Whole genome sequencing of liver biopsy	1 year
Secondary	Microbiome: Feces metatranscriptomics	Microbiome measurements on feces	1 year
Secondary	Microbiome: Urine metatranscriptomics	Microbiome measurements on urine	1 year
Secondary	Microbiome: Saliva metatranscriptomics	Microbiome measurements on saliva	1 year
Secondary	Microbiome: Urine Next Generation Sequencing of microbial DNA	Microbiome measurements on urine	1 year
Secondary	Microbiome: Feces Next Generation Sequencing of microbial DNA	Microbiome measurements on feces	1 year
Secondary	Microbiome: Saliva Next Generation Sequencing of microbial DNA	Microbiome measurements on saliva	1 year
Secondary	Microbiome: Saliva metabolomics	Microbiome measurements on saliva	1 year
Secondary	Microbiome: Urine metabolomics	Microbiome measurements on urine	1 year
Secondary	Microbiome: Feces metabolomics	Microbiome measurements on feces	1 year
Secondary	Microbiome: Saliva proteomics	Microbiome measurements on saliva	1 year
Secondary	Microbiome: Urine proteomics	Microbiome measurements on urine	1 year
Secondary	Microbiome: Feces proteomics	Microbiome measurements on feces	1 year
Secondary	Genetics: Whole genome sequencing of blood	Whole genome sequencing of blood	2 years
Secondary	Genetics: Whole genome sequencing of liver biopsy	Whole genome sequencing of liver biopsy	2 years
Secondary	Microbiome: Feces metatranscriptomics	Microbiome measurements on feces	2 years
Secondary	Microbiome: Urine metatranscriptomics	Microbiome measurements on urine	2 years
Secondary	Microbiome: Saliva metatranscriptomics	Microbiome measurements on saliva	2 years
Secondary	Microbiome: Saliva metabolomics	Microbiome measurements on saliva	2 years
Secondary	Microbiome: Feces metabolomics	Microbiome measurements on feces	2 years
Secondary	Microbiome: Urine metabolomics	Microbiome measurements on urine	2 years
Secondary	Microbiome: Urine proteomics	Microbiome measurements on urine	2 years
Secondary	Microbiome: Feces proteomics	Microbiome measurements on feces	2 years
Secondary	Microbiome: Saliva proteomics	Microbiome measurements on saliva	2 years
Secondary	Microbiome: Urine Next Generation Sequencing of microbial DNA	Microbiome measurements on urine	2 years
Secondary	Microbiome: Saliva Next Generation Sequencing of microbial DNA	Microbiome measurements on saliva	2 years
Secondary	Microbiome: Feces Next Generation Sequencing of microbial DNA	Microbiome measurements on feces	2 years
Secondary	Genetics: Whole genome sequencing of blood	Whole genome sequencing of blood	6 years
Secondary	Genetics: Whole genome sequencing of liver biopsy	Whole genome sequencing of liver biopsy	6 years
Secondary	Microbiome: Feces Next Generation Sequencing of microbial DNA	Microbiome measurements on feces	6 years
Secondary	Microbiome: Feces metatranscriptomics	Microbiome measurements on feces	6 years
Secondary	Microbiome: Feces metabolomics	Microbiome measurements on feces	6 years
Secondary	Microbiome: Feces proteomics	Microbiome measurements on feces	6 years
Secondary	Microbiome: Urine Next Generation Sequencing of microbial DNA	Microbiome measurements on urine	6 years
Secondary	Microbiome: Urine metatranscriptomics	Microbiome measurements on urine	6 years
Secondary	Microbiome: Urine metabolomics	Microbiome measurements on urine	6 years
Secondary	Microbiome: Urine proteomics	Microbiome measurements on urine	6 years
Secondary	Microbiome: Saliva Next Generation Sequencing of microbial DNA	Microbiome measurements on saliva	6 years
Secondary	Microbiome: Saliva metatranscriptomics	Microbiome measurements on saliva	6 years
Secondary	Microbiome: Saliva metabolomics	Microbiome measurements on saliva	6 years
Secondary	Microbiome: Saliva proteomics	Microbiome measurements on saliva	6 years
Secondary	Genetics: Whole genome sequencing of blood	Whole genome sequencing of blood	11 years
Secondary	Genetics: Whole genome sequencing of liver biopsy	Whole genome sequencing of liver biopsy	11 years
Secondary	Microbiome: Feces Next Generation Sequencing of microbial DNA	Microbiome measurements on feces	11 years
Secondary	Microbiome: Feces metatranscriptomics	Microbiome measurements on feces	11 years
Secondary	Microbiome: Feces metabolomics	Microbiome measurements on feces	11 years
Secondary	Microbiome: Feces proteomics	Microbiome measurements on feces	11 years
Secondary	Microbiome: Urine Next Generation Sequencing of microbial DNA	Microbiome measurements on urine	11 years
Secondary	Microbiome: Urine metatranscriptomics	Microbiome measurements on urine	11 years
Secondary	Microbiome: Urine metabolomics	Microbiome measurements on urine	11 years
Secondary	Microbiome: Urine proteomics	Microbiome measurements on urine	11 years
Secondary	Microbiome: Saliva Next Generation Sequencing of microbial DNA	Microbiome measurements on saliva	11 years
Secondary	Microbiome: Saliva metatranscriptomics	Microbiome measurements on saliva	11 years
Secondary	Microbiome: Saliva metabolomics	Microbiome measurements on saliva	11 years
Secondary	Microbiome: Saliva proteomics	Microbiome measurements on saliva	11 years
Secondary	Genetics: Whole genome sequencing of blood	Whole genome sequencing of blood	16 years
Secondary	Genetics: Whole genome sequencing of liver biopsy	Whole genome sequencing of liver biopsy	16 years
Secondary	Microbiome: Feces metatranscriptomics	Microbiome measurements on feces	16 years
Secondary	Microbiome: Feces Next Generation Sequencing of microbial DNA	Microbiome measurements on feces	16 years
Secondary	Microbiome: Feces metabolomics	Microbiome measurements on feces	16 years
Secondary	Microbiome: Feces proteomics	Microbiome measurements on feces	16 years
Secondary	Microbiome: Urine metatranscriptomics	Microbiome measurements on urine	16 years
Secondary	Microbiome: Urine Next Generation Sequencing of microbial DNA	Microbiome measurements on urine	16 years
Secondary	Microbiome: Urine metabolomics	Microbiome measurements on urine	16 years
Secondary	Microbiome: Urine proteomics	Microbiome measurements on urine	16 years
Secondary	Microbiome: Saliva metatranscriptomics	Microbiome measurements on saliva	16 years
Secondary	Microbiome: Saliva Next Generation Sequencing of microbial DNA	Microbiome measurements on saliva	16 years
Secondary	Microbiome: Saliva metabolomics	Microbiome measurements on saliva	16 years
Secondary	Microbiome: Saliva proteomics	Microbiome measurements on saliva	16 years
Secondary	Status of the cardiac system: Ultrasound of the heart	% of patients with anatomic anomalies on ultrasound of the heart	Inclusion
Secondary	Status of the cardiac system: MRI of the lymph system	% of patients with central lymph system anomaly	Inclusion
Secondary	Status of the cardiac system: Near Infrared Fluorescence of the lymph system	Near Infrared Fluorescence of the lymph system	Inclusion
Secondary	Status of the cardiac system: Ultrasound of the heart	% of patients with anatomic anomalies on ultrasound of the heart	1 year
Secondary	Status of the cardiac system: MRI of the lymph system	% of patients with central lymph system anomaly	1 year
Secondary	Status of the cardiac system: Near Infrared Fluorescence of the lymph system	Near Infrared Fluorescence of the lymph system	1 year
Secondary	Status of the cardiac system: Ultrasound of the heart	% of patients with anatomic anomalies on ultrasound of the heart	2 years
Secondary	Status of the cardiac system: MRI of the lymph system	% of patients with central lymph system anomaly	2 years
Secondary	Status of the cardiac system: Near Infrared Fluorescence of the lymph system	Near Infrared Fluorescence of the lymph system	2 years
Secondary	Status of the cardiac system: Ultrasound of the heart	% of patients with anatomic anomalies on ultrasound of the heart	6 years
Secondary	Status of the cardiac system: MRI of the lymph system	% of patients with central lymph system anomaly	6 years
Secondary	Status of the cardiac system: Near Infrared Fluorescence of the lymph system	Near Infrared Fluorescence of the lymph system	6 years
Secondary	Status of the cardiac system: Ultrasound of the heart	% of patients with anatomic anomalies on ultrasound of the heart	11 years
Secondary	Status of the cardiac system: MRI of the lymph system	% of patients with central lymph system anomaly	11 years
Secondary	Status of the cardiac system: Near Infrared Fluorescence of the lymph system	Near Infrared Fluorescence of the lymph system	11 years
Secondary	Status of the cardiac system: Ultrasound of the heart	% of patients with anatomic anomalies on ultrasound of the heart	16 years
Secondary	Status of the cardiac system: MRI of the lymph system	% of patients with central lymph system anomaly	16 years
Secondary	Status of the cardiac system: Near Infrared Fluorescence of the lymph system	Near Infrared Fluorescence of the lymph system	16 years
Secondary	Level of Physical activity	Accelerometer measurements	Inclusion
Secondary	Level of Physical activity	Accelerometer measurements	1 year
Secondary	Level of Physical activity	Accelerometer measurements	2 years
Secondary	Level of Physical activity	Accelerometer measurements	6 years
Secondary	Level of Physical activity	Accelerometer measurements	11 years
Secondary	Level of Physical activity	Accelerometer measurements	16 years
Secondary	Ultrasound of liver and bile ducts with elastography	% of patients with liver fibrosis measured with ultrasound	Inclusion
Secondary	Liver biopsy	Level of liver fibrosis (grade 0-4)	Inclusion
Secondary	FGF-19; Fibroblast growth factor 19	Liver fibrosis status	Inclusion
Secondary	ELF-score: Enhanced Liver Fibrosis	Liver fibrosis status	Inclusion
Secondary	INR: international normalized ratio	Standard liver evaluation	Inclusion
Secondary	prothrombin+proconvertin (PP)	Standard liver evaluation	Inclusion
Secondary	ALAT: alanine transaminase	Standard liver evaluation	Inclusion
Secondary	GGT: Gamma-glutamyl transferase	Standard liver evaluation	Inclusion
Secondary	Bilirubin	Standard liver evaluation	Inclusion
Secondary	ASAT: Aspartate transaminase	Standard liver evaluation	Inclusion
Secondary	Alkaline phosphatase	Standard liver evaluation	Inclusion
Secondary	Ammonia	Standard liver evaluation	Inclusion
Secondary	Thrombocytes	Standard liver evaluation	Inclusion
Secondary	Ultrasound of liver and bile ducts with elastography	% of patients with liver fibrosis measured with ultrasound	1 year
Secondary	FGF-19: Fibroblast growth factor 19	Liver fibrosis status	1 year
Secondary	ELF-score: Enhanced Liver Fibrosis	Liver fibrosis status	1 year
Secondary	INR: international normalized ratio	Standard liver evaluation	1 year
Secondary	prothrombin+proconvertin (PP)	Standard liver evaluation	1 year
Secondary	ALAT: alanine transaminase	Standard liver evaluation	1 year
Secondary	ASAT: Aspartate transaminase	Standard liver evaluation	1 year
Secondary	GGT: Gamma-glutamyl transferase	Standard liver evaluation	1 year
Secondary	Bilirubin	Standard liver evaluation	1 year
Secondary	Alkaline phosphatase	Standard liver evaluation	1 year
Secondary	Ammonia	Standard liver evaluation	1 year
Secondary	Thrombocytes	Standard liver evaluation	1 year
Secondary	Liver biopsy	Level of liver fibrosis (grade 0-4)	1 year
Secondary	Ultrasound of liver and bile ducts with elastography	% of patients with liver fibrosis measured with ultrasound	2 years
Secondary	FGF-19: Fibroblast growth factor 19	Liver fibrosis status	2 years
Secondary	ELF-score: Enhanced Liver Fibrosis	Liver fibrosis status	2 years
Secondary	Liver biopsy	Level of liver fibrosis (grade 0-4)	2 years
Secondary	INR: international normalized ratio	Standard liver evaluation	2 years
Secondary	prothrombin+proconvertin (PP)	Standard liver evaluation	2 years
Secondary	ALAT: alanine transaminase	Standard liver evaluation	2 years
Secondary	ASAT: Aspartate transaminase	Standard liver evaluation	2 years
Secondary	GGT: Gamma-glutamyl transferase	Standard liver evaluation	2 years
Secondary	Alkaline phosphatase	Standard liver evaluation	2 years
Secondary	Bilirubin	Standard liver evaluation	2 years
Secondary	Ammonia	Standard liver evaluation	2 years
Secondary	Thrombocytes	Standard liver evaluation	2 years
Secondary	Ultrasound of liver and bile ducts with elastography	% of patients with liver fibrosis measured with ultrasound	6 years
Secondary	Liver biopsy	Level of liver fibrosis (grade 0-4)	6 years
Secondary	ELF-score: Enhanced Liver Fibrosis	Liver fibrosis status	6 years
Secondary	FGF-19: Fibroblast growth factor 19	Liver fibrosis status	6 years
Secondary	INR: international normalized ratio	Standard liver evaluation	6 years
Secondary	prothrombin+proconvertin (PP)	Standard liver evaluation	6 years
Secondary	ALAT: alanine transaminase	Standard liver evaluation	6 years
Secondary	ASAT: Aspartate transaminase	Standard liver evaluation	6 years
Secondary	GGT: Gamma-glutamyl transferase	Standard liver evaluation	6 years
Secondary	Bilirubin	Standard liver evaluation	6 years
Secondary	Alkaline phosphatase	Standard liver evaluation	6 years
Secondary	Ammonia	Standard liver evaluation	6 years
Secondary	Thrombocytes	Standard liver evaluation	6 years
Secondary	Ultrasound of liver and bile ducts with elastography	% of patients with liver fibrosis measured with ultrasound	11 years
Secondary	Liver biopsy	Level of liver fibrosis (grade 0-4)	11 years
Secondary	FGF-19: Fibroblast growth factor 19	Liver fibrosis status	11 years
Secondary	ELF-score: Enhanced Liver Fibrosis	Liver fibrosis status	11 years
Secondary	INR: international normalized ratio	Standard liver evaluation	11 years
Secondary	prothrombin+proconvertin (PP)	Standard liver evaluation	11 years
Secondary	ALAT: alanine transaminase	Standard liver evaluation	11 years
Secondary	ASAT: Aspartate transaminase	Standard liver evaluation	11 years
Secondary	GGT: Gamma-glutamyl transferase	Standard liver evaluation	11 years
Secondary	Bilirubin	Standard liver evaluation	11 years
Secondary	Alkaline phosphatase	Standard liver evaluation	11 years
Secondary	Ammonia	Standard liver evaluation	11 years
Secondary	Thrombocytes	Standard liver evaluation	11 years
Secondary	Ultrasound of liver and bile ducts with elastography	% of patients with liver fibrosis measured with ultrasound	16 years
Secondary	Liver biopsy	Level of liver fibrosis (grade 0-4)	16 years
Secondary	FGF-19: Fibroblast growth factor 19	Liver fibrosis status	16 years
Secondary	ELF-score: Enhanced Liver Fibrosis	Liver fibrosis status	16 years
Secondary	INR: international normalized ratio	Standard liver evaluation	16 years
Secondary	prothrombin+proconvertin (PP)	Standard liver evaluation	16 years
Secondary	ALAT: alanine transaminase	Standard liver evaluation	16 years
Secondary	ASAT: Aspartate transaminase	Standard liver evaluation	16 years
Secondary	GGT: Gamma-glutamyl transferase	Standard liver evaluation	16 years
Secondary	Bilirubin	Standard liver evaluation	16 years
Secondary	Alkaline phosphatase	Standard liver evaluation	16 years
Secondary	Ammonia	Standard liver evaluation	16 years
Secondary	Thrombocytes	Standard liver evaluation	16 years
Secondary	Clinical examination: Cirrhosis stigmata	Incidence of spider angioma	Inclusion
Secondary	Clinical examination: Cirrhosis stigmata	Incidence of spider angioma	1 year
Secondary	Clinical examination: Cirrhosis stigmata	Incidence of spider angioma	2 years
Secondary	Clinical examination: Cirrhosis stigmata	Incidence of spider angioma	6 years
Secondary	Clinical examination: Cirrhosis stigmata	Incidence of spider angioma	11 years
Secondary	Clinical examination: Cirrhosis stigmata	Incidence of spider angioma	16 years
Secondary	Clinical examination: Cirrhosis stigmata	Incidence of ascitis	Inclusion
Secondary	Clinical examination: Cirrhosis stigmata	Incidence of ascitis	1 year
Secondary	Clinical examination: Cirrhosis stigmata	Incidence of ascitis	2 years
Secondary	Clinical examination: Cirrhosis stigmata	Incidence of ascitis	6 years
Secondary	Clinical examination: Cirrhosis stigmata	Incidence of ascitis	11 years
Secondary	Clinical examination: Cirrhosis stigmata	Incidence of ascitis	16 years
Secondary	Clinical examination: Cirrhosis stigmata	Incidence of palmar erythema	Inclusion
Secondary	Clinical examination: Cirrhosis stigmata	Incidence of palmar erythema	1 year
Secondary	Clinical examination: Cirrhosis stigmata	Incidence of palmar erythema	2 years
Secondary	Clinical examination: Cirrhosis stigmata	Incidence of palmar erythema	6 years
Secondary	Clinical examination: Cirrhosis stigmata	Incidence of palmar erythema	11 years
Secondary	Clinical examination: Cirrhosis stigmata	Incidence of palmar erythema	16 years
Secondary	Anthropometry: Length	cm	Inclusion
Secondary	Anthropometry: Length	cm	1 year
Secondary	Anthropometry: Length	cm	2 years
Secondary	Anthropometry: Height	cm	6 years
Secondary	Anthropometry: Height	cm	11 years
Secondary	Anthropometry: Height	cm	16 years
Secondary	Anthropometry: Weight	kg	Inclusion
Secondary	Anthropometry: Weight	kg	1 year
Secondary	Anthropometry: Weight	kg	2 years
Secondary	Anthropometry: Weight	kg	6 years
Secondary	Anthropometry: Weight	kg	11 years
Secondary	Anthropometry: Weight	kg	16 years
Secondary	Anthropometry: Mid-upper arm circumference (MUAC)	mm	Inclusion
Secondary	Anthropometry: Mid-upper arm circumference (MUAC)	mm	1 year
Secondary	Anthropometry: Mid-upper arm circumference (MUAC)	mm	2 years
Secondary	Anthropometry: Mid-upper arm circumference (MUAC)	mm	6 years
Secondary	Anthropometry: Mid-upper arm circumference (MUAC)	mm	11 years
Secondary	Anthropometry: Mid-upper arm circumference (MUAC)	mm	16 years
Secondary	Anthropometry: Head circumference	cm	Inclusion
Secondary	Anthropometry: Head circumference	cm	1 year
Secondary	Anthropometry: Head circumference	cm	2 years
Secondary	Anthropometry: Head circumference	cm	6 years
Secondary	Anthropometry: Head circumference	cm	11 years
Secondary	Anthropometry: Head circumference	cm	16 years
Secondary	Essential fatty acids		Inclusion
Secondary	Essential fatty acids		1 year
Secondary	Essential fatty acids		2 years
Secondary	Essential fatty acids		6 years
Secondary	Essential fatty acids		11 years
Secondary	Essential fatty acids		16 years
Secondary	IGF-1	Insulin-like growth factor 1	Inclusion
Secondary	IGF-1	Insulin-like growth factor 1	1 year
Secondary	IGF-1	Insulin-like growth factor 1	2 years
Secondary	IGF-1	Insulin-like growth factor 1	6 years
Secondary	IGF-1	Insulin-like growth factor 1	11 years
Secondary	IGF-1	Insulin-like growth factor 1	16 years
Secondary	Meal stimulation measuring incretin		Inclusion
Secondary	Meal stimulation measuring incretin		1 year
Secondary	Meal stimulation measuring incretin		2 years
Secondary	Meal stimulation measuring incretin		6 years
Secondary	Meal stimulation measuring incretin		11 years
Secondary	Meal stimulation measuring incretin		16 years
Secondary	Bile acid		Inclusion
Secondary	Bile acid		1 year
Secondary	Bile acid		2 years
Secondary	Bile acid		6 years
Secondary	Bile acid		11 years
Secondary	Bile acid		16 years
Secondary	Autotaxin		Inclusion
Secondary	Autotaxin		1 year
Secondary	Autotaxin		2 years
Secondary	Autotaxin		6 years
Secondary	Autotaxin		11 years
Secondary	Autotaxin		16 years
Secondary	EDTA clearance	Glomerular Filtration Rate Measured by 51 Cr-EDTA Clearance	Inclusion
Secondary	EDTA clearance	Glomerular Filtration Rate Measured by 51 Cr-EDTA Clearance	1 year
Secondary	EDTA clearance	Glomerular Filtration Rate Measured by 51 Cr-EDTA Clearance	2 years
Secondary	EDTA clearance	Glomerular Filtration Rate Measured by 51 Cr-EDTA Clearance	6 years
Secondary	EDTA clearance	Glomerular Filtration Rate Measured by 51 Cr-EDTA Clearance	11 years
Secondary	EDTA clearance	Glomerular Filtration Rate Measured by 51 Cr-EDTA Clearance	16 years
Secondary	Vaccination status	Level of antibodies	Inclusion
Secondary	Vaccination status	Level of antibodies	1 year
Secondary	Vaccination status	Level of antibodies	2 years
Secondary	Vaccination status	Level of antibodies	6 years
Secondary	Vaccination status	Level of antibodies	11 years
Secondary	Vaccination status	Level of antibodies	16 years
Secondary	Immunoresponse: RTE	Recent thymic emigrants	Inclusion
Secondary	Immunoresponse: RTE	Recent thymic emigrants	1 year
Secondary	Immunoresponse: RTE	Recent thymic emigrants	2 years
Secondary	Immunoresponse: RTE	Recent thymic emigrants	6 years
Secondary	Immunoresponse: RTE	Recent thymic emigrants	11 years
Secondary	Immunoresponse: RTE	Recent thymic emigrants	16 years
Secondary	Immunoresponse: Flow panel	T-cell differentiation	Inclusion
Secondary	Immunoresponse: Flow panel	T-cell differentiation	1 year
Secondary	Immunoresponse: Flow panel	T-cell differentiation	2 years
Secondary	Immunoresponse: Flow panel	T-cell differentiation	6 years
Secondary	Immunoresponse: Flow panel	T-cell differentiation	11 years
Secondary	Immunoresponse: Flow panel	T-cell differentiation	16 years
Secondary	Immunoresponse: Immunoglobulin		Inclusion
Secondary	Immunoresponse: Immunoglobulin		1 year
Secondary	Immunoresponse: Immunoglobulin		2 years
Secondary	Immunoresponse: Immunoglobulin		6 years
Secondary	Immunoresponse: Immunoglobulin		11 years
Secondary	Immunoresponse: Immunoglobulin		16 years
Secondary	Immunoresponse: Somatic hyper mutation		Inclusion
Secondary	Immunoresponse: Somatic hyper mutation		1 year
Secondary	Immunoresponse: Somatic hyper mutation		2 years
Secondary	Immunoresponse: Somatic hyper mutation		6 years
Secondary	Immunoresponse: Somatic hyper mutation		11 years
Secondary	Immunoresponse: Somatic hyper mutation		16 years
Secondary	Epstein-Barr Virus (EBV)	level of EBV DNA present	Inclusion
Secondary	Epstein-Barr Virus (EBV)	level of EBV DNA present	1 year
Secondary	Epstein-Barr Virus (EBV)	level of EBV DNA present	2 years
Secondary	Epstein-Barr Virus (EBV)	level of EBV DNA present	6 years
Secondary	Epstein-Barr Virus (EBV)	level of EBV DNA present	11 years
Secondary	Epstein-Barr Virus (EBV)	level of EBV DNA present	16 years
Secondary	Cytomegalovirus (CMV)	level of CMV DNA present	Inclusion
Secondary	Cytomegalovirus (CMV)	level of CMV DNA present	1 year
Secondary	Cytomegalovirus (CMV)	level of CMV DNA present	2 years
Secondary	Cytomegalovirus (CMV)	level of CMV DNA present	6 years
Secondary	Cytomegalovirus (CMV)	level of CMV DNA present	11 years
Secondary	Cytomegalovirus (CMV)	level of CMV DNA present	16 years
Secondary	Hepatobiliary scintigraphy	Hepatic extraction fraction	Inclusion
Secondary	Hepatobiliary scintigraphy	Hepatic extraction fraction	1 year
Secondary	Hepatobiliary scintigraphy	Hepatic extraction fraction	2 years
Secondary	Hepatobiliary scintigraphy	Hepatic extraction fraction	6 years
Secondary	Hepatobiliary scintigraphy	Hepatic extraction fraction	11 years
Secondary	Hepatobiliary scintigraphy	Hepatic extraction fraction	16 years
Secondary	MRI of liver and bile ducts with elastography	Liver stiffness	Inclusion
Secondary	MRI of liver and bile ducts with elastography	Liver stiffness	1 year
Secondary	MRI of liver and bile ducts with elastography	Liver stiffness	2 years
Secondary	MRI of liver and bile ducts with elastography	Liver stiffness	6 years
Secondary	MRI of liver and bile ducts with elastography	Liver stiffness	11 years
Secondary	MRI of liver and bile ducts with elastography	Liver stiffness	16 years
Secondary	Fibroscan	Liver stiffness (number)	Inclusion
Secondary	Fibroscan	Liver stiffness (number)	1 year
Secondary	Fibroscan	Liver stiffness (number)	2 years
Secondary	Fibroscan	Liver stiffness (number)	6 years
Secondary	Fibroscan	Liver stiffness (number)	11 years
Secondary	Fibroscan	Liver stiffness (number)	16 years
Secondary	Indocyanine green clearance		Inclusion
Secondary	Indocyanine green clearance		1 year
Secondary	Indocyanine green clearance		2 years
Secondary	Indocyanine green clearance		6 years
Secondary	Indocyanine green clearance		11 years
Secondary	Indocyanine green clearance		16 years
Secondary	Fecal fat measurements		Inclusion
Secondary	Fecal fat measurements		1 year
Secondary	Fecal fat measurements		2 years
Secondary	Fecal fat measurements		6 years
Secondary	Fecal fat measurements		11 years
Secondary	Fecal fat measurements		16 years
Secondary	Thymus scan with ultrasound	Thymic index (measurement of size)	Inclusion
Secondary	Thymus scan with ultrasound	Thymic index (measurement of size)	1 year
Secondary	Thymus scan with ultrasound	Thymic index (measurement of size)	2 years
Secondary	Thymus scan with ultrasound	Thymic index (measurement of size)	6 years
Secondary	Thymus scan with ultrasound	Thymic index (measurement of size)	11 years
Secondary	Thymus scan with ultrasound	Thymic index (measurement of size)	16 years
Secondary	DEXA scan	Dual energy x-ray absorptiometry	Inclusion
Secondary	DEXA scan	Dual energy x-ray absorptiometry	1 year
Secondary	DEXA scan	Dual energy x-ray absorptiometry	2 years
Secondary	DEXA scan	Dual energy x-ray absorptiometry	6 years
Secondary	DEXA scan	Dual energy x-ray absorptiometry	11 years
Secondary	DEXA scan	Dual energy x-ray absorptiometry	16 years
Secondary	PEDS-QL	Pediatric Quality of Life Inventory Higher scores indicate better quality of life, from 0-100	Inclusion
Secondary	PEDS-QL	Pediatric Quality of Life Inventory Higher scores indicate better quality of life, from 0-100	1 year
Secondary	PEDS-QL	Pediatric Quality of Life Inventory Higher scores indicate better quality of life, from 0-100	2 years
Secondary	PEDS-QL	Pediatric Quality of Life Inventory Higher scores indicate better quality of life, from 0-100	6 years
Secondary	PEDS-QL	Pediatric Quality of Life Inventory Higher scores indicate better quality of life, from 0-100	11 years
Secondary	PEDS-QL	Pediatric Quality of Life Inventory Higher scores indicate better quality of life, from 0-100	16 years
Secondary	Leptin		Inclusion
Secondary	Leptin		1 year
Secondary	Leptin		2 years
Secondary	Leptin		6 years
Secondary	Leptin		11 years
Secondary	Leptin		16 years