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

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

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

Study Overview

• Status: Recruiting
• Conditions: Cognitive Impairment; Biliary Atresia
• Intervention / Treatment: Other: Neurocognitive monitoring

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Vibeke Brix Christensen, MD, PhD, DMSc; Phone Number: +4535458842; Email: vibeke.brix.christensen@regionh.dk

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • Recruiting
    • Rigshospitalet
    • Contact: Vibeke Brix Christensen, MD, PhD, DMSc; Phone Number: +4535458842; Email: vibeke.brix.christensen@regionh.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 18 years (ADULT, CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Children with biliary atresia (BA), children with Tetralogy of Fallot (ToF) and healthy control children between the age of 0-17 years. The BA and ToF children were recruited from their respective outpatient clinics at Rigshospitalet, Denmark, which is the only centre treating these patients. Healthy controls were siblings to BA children, recruited from staffs children and friends or recruited from a general practitioners office in Nivaa, Denmark. The recruitment took place from March 2020 and is ongoing

Description

Inclusion Criteria:

• Biliary atresia
• Tetralogy of Fallot
• Healthy controls

Exclusion Criteria:

- Not able to participate in exams

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Children with biliary atresia	Other: Neurocognitive monitoring; Neurocognitive tests and MRI of the brain
Children with Tetralogy of Fallot	Other: Neurocognitive monitoring; Neurocognitive tests and MRI of the brain
Healthy control children	Other: Neurocognitive monitoring; Neurocognitive tests and MRI of the brain

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MRI of the brain	% of patients with anatomic anomalies on MRI of the brain	Inclusion
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
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
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
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
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
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
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
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
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
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
Neurocognitive status: CANTAB	Neurocognitive test panel depending on age at inclusion: CANTAB if inclusion between 6-18 years Cambridge Neuropsychological Test Automated Battery	Inclusion
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
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
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
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
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
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
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
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
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
MRI of the brain	% of patients with anatomic anomalies on MRI of the brain	1 year
Neurocognitive status: Alberta Infant Motor Scale	Alberta Infant Motor Scale Percentile, highest is the best	1 year
Neurocognitive status: Bayley Scales of Development III	Bayley Scales of Development III From 0-200, highest is best	1 year
Neurocognitive status: BRIEF 1	BRIEF 1 Behaviour Rating Inventory of Executive Function, percentile, lowest is best	1 year
Neurocognitive status: CBCL	CBCL Child Behavior Checklist, percentile, lowest is best	1 year
Neurocognitive status: Kiddie-Sads	Kiddie-Sads Kiddie Schedule for Affective Disorders and Schizophrenia, 0-61, lowest is best	1 year
MRI of the brain	% of patients with anatomic anomalies on MRI of the brain	2 years
Neurocognitive status: Bayley Scales of Development III	Bayley Scales of Development III From 0-200, highest is best	2 years
Neurocognitive status: BRIEF 1	BRIEF 1 Behaviour Rating Inventory of Executive Function, percentile, lowest is best	2 years
Neurocognitive status: CBCL	CBCL Child Behavior Checklist, percentile, lowest is best	2 years
Neurocognitive status: Kiddie-Sads	Kiddie-Sads Kiddie Schedule for Affective Disorders and Schizophrenia, 0-61, lowest is best	2 years
Neurocognitive status: ADHD	ADHD Lowest is best, 0-78	2 years
Neurocognitive status: Vineland	Vineland Adaptive Behavior Scales, 20 to 160, highest is best	2 years
MRI of the brain	% of patients with anatomic anomalies on MRI of the brain	6 years
Neurocognitive: Movement ABC	Neurocognitive test panel depending on age Movement Assessment Battery for Children, mean 10 SD 3, highest is best	6 years
Neurocognitive status: WISC-IV	WISC-IV Wechsler Intelligence Scale for Children, 40 to 160, highest is best	6 years
Neurocognitive status: Auditory Verbal Learning Test/ToMaL	Auditory Verbal Learning Test/ToMaL Mean 10 SD 3, highest is best	6 years
Neurocognitive status: TEA-Ch	TEA-Ch Test of Everyday Attention for Children, normalized to z-score, highest is best	6 years
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
Neurocognitive status: Test of Visual Perceptual Skills	Test of Visual Perceptual Skills Percentile, highest is best	6 years
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
Neurocognitive status: CANTAB	CANTAB Cambridge Neuropsychological Test Automated Battery	6 years
Neurocognitive status: BRIEF 2	BRIEF 2 Behaviour Rating Inventory of Executive Function, percentile, lowest is best	6 years
Neurocognitive status: ADHD screening	ADHD screening Lowest is best, 0-78	6 years
Neurocognitive status: SRS-2	SRS-2 Social Responsiveness Scale, 32-114. lowest is best	6 years
Neurocognitive status: Kiddie-Sads	Kiddie-Sads Kiddie Schedule for Affective Disorders and Schizophrenia, 0-61, lowest is best	6 years
Neurocognitive status: CBCL	CBCL Child Behavior Checklist, percentile, lowest is best	6 years
Neurocognitive status: Vineland	Vineland Vineland Adaptive Behavior Scales, 20 to 160, highest is best	6 years
MRI of the brain	% of patients with anatomic anomalies on MRI of the brain	11 years
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
Neurocognitive status: WISC-IV	WISC-IV Wechsler Intelligence Scale for Children, 40 to 160, highest is best	11 years
Neurocognitive status: Auditory Verbal Learning Test/ToMaL	Auditory Verbal Learning Test/ToMaL Mean 10 SD 3, highest is best	11 years
Neurocognitive status:TEA-Ch	TEA-Ch Test of Everyday Attention for Children, normalized to z-score, highest is best	11 years
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
Neurocognitive status: Test of Visual Perceptual Skills	Test of Visual Perceptual Skills Percentile, highest is best	11 years
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
Neurocognitive status: CANTAB	CANTAB Cambridge Neuropsychological Test Automated Battery	11 years
Neurocognitive status: BRIEF 2	BRIEF 2 Behaviour Rating Inventory of Executive Function, percentile, lowest is best	11 years
Neurocognitive status: ADHD screening	ADHD screening Lowest is best, 0-78	11 years
Neurocognitive status: SRS-2	SRS-2 Social Responsiveness Scale, 32-114. lowest is best	11 years
Neurocognitive status: Kiddie-Sads	Kiddie-Sads Kiddie Schedule for Affective Disorders and Schizophrenia, 0-61, lowest is best	11 years
Neurocognitive status: CBCL	CBCL Child Behavior Checklist, percentile, lowest is best	11 years
Neurocognitive status: Vineland	Vineland Adaptive Behavior Scales, 20 to 160, highest is best	11 years
MRI of the brain	% of patients with anatomic anomalies on MRI of the brain	16 years
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
Neurocognitive status: WISC-IV	WISC-IV Wechsler Adult Intelligence Scale, 40-160, highest is best	16 years
Neurocognitive status: Auditory Verbal Learning Test/ToMaL	Auditory Verbal Learning Test/ToMaL Mean 10 SD 3, highest is best	16 years
Neurocognitive status: TEA-Ch	TEA-Ch Test of Everyday Attention for Children, normalized to z-score, highest is best	16 years
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
Neurocognitive status: Test of Visual Perceptual Skills	Test of Visual Perceptual Skills Percentile, highest is best	16 years
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
Neurocognitive status: CANTAB	CANTAB Cambridge Neuropsychological Test Automated Battery	16 years
Neurocognitive status: BRIEF 2	BRIEF 2 Behaviour Rating Inventory of Executive Function, percentile, lowest is best	16 years
Neurocognitive status: ADHD screening	ADHD screening Lowest is best, 0-78	16 years
Neurocognitive status: SRS-2	SRS-2 Social Responsiveness Scale, 32-114. lowest is best	16 years
Neurocognitive status: Kiddie-Sads	Kiddie-Sads Kiddie Schedule for Affective Disorders and Schizophrenia, 0-61, lowest is best	16 years
Neurocognitive status: CBCL	CBCL Child Behavior Checklist, percentile, lowest is best	16 years
Neurocognitive status: Vineland	Vineland Adaptive Behavior Scales, 20 to 160, highest is best	16 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Genetics: Whole genome sequencing of blood	Whole genome sequencing of blood	Inclusion
Genetics: Whole genome sequencing of liver biopsy	Whole genome sequencing of liver biopsy	Inclusion
Microbiome: Urine proteomics	Microbiome measurements on urine	Inclusion
Microbiome: Feces proteomics	Microbiome measurements on feces	Inclusion
Microbiome: Saliva proteomics	Microbiome measurements on saliva	Inclusion
Microbiome: Feces Next Generation Sequencing of microbial DNA	Microbiome measurement on feces	Inclusion
Microbiome: Urine Next Generation Sequencing of microbial DNA	Microbiome measurement on urine	Inclusion
Microbiome: Saliva Next Generation Sequencing of microbial DNA	Microbiome measurement on saliva	Inclusion
Microbiome: Feces metabolomics	Microbiome measurements on feces	Inclusion
Microbiome: Urine metabolomics	Microbiome measurements on urine	Inclusion
Microbiome: Saliva metabolomics	Microbiome measurements on saliva	Inclusion
Microbiome: Feces metatranscriptomics	Microbiome measurements on feces	Inclusion
Microbiome: Urine metatranscriptomics	Microbiome measurements on urine	Inclusion
Microbiome: Saliva metatranscriptomics	Microbiome measurements on saliva	Inclusion
Genetics: Whole genome sequencing of blood	Whole genome sequencing of blood	1 year
Genetics: Whole genome sequencing of liver biopsy	Whole genome sequencing of liver biopsy	1 year
Microbiome: Feces metatranscriptomics	Microbiome measurements on feces	1 year
Microbiome: Urine metatranscriptomics	Microbiome measurements on urine	1 year
Microbiome: Saliva metatranscriptomics	Microbiome measurements on saliva	1 year
Microbiome: Urine Next Generation Sequencing of microbial DNA	Microbiome measurements on urine	1 year
Microbiome: Feces Next Generation Sequencing of microbial DNA	Microbiome measurements on feces	1 year
Microbiome: Saliva Next Generation Sequencing of microbial DNA	Microbiome measurements on saliva	1 year
Microbiome: Saliva metabolomics	Microbiome measurements on saliva	1 year
Microbiome: Urine metabolomics	Microbiome measurements on urine	1 year
Microbiome: Feces metabolomics	Microbiome measurements on feces	1 year
Microbiome: Saliva proteomics	Microbiome measurements on saliva	1 year
Microbiome: Urine proteomics	Microbiome measurements on urine	1 year
Microbiome: Feces proteomics	Microbiome measurements on feces	1 year
Genetics: Whole genome sequencing of blood	Whole genome sequencing of blood	2 years
Genetics: Whole genome sequencing of liver biopsy	Whole genome sequencing of liver biopsy	2 years
Microbiome: Feces metatranscriptomics	Microbiome measurements on feces	2 years
Microbiome: Urine metatranscriptomics	Microbiome measurements on urine	2 years
Microbiome: Saliva metatranscriptomics	Microbiome measurements on saliva	2 years
Microbiome: Saliva metabolomics	Microbiome measurements on saliva	2 years
Microbiome: Feces metabolomics	Microbiome measurements on feces	2 years
Microbiome: Urine metabolomics	Microbiome measurements on urine	2 years
Microbiome: Urine proteomics	Microbiome measurements on urine	2 years
Microbiome: Feces proteomics	Microbiome measurements on feces	2 years
Microbiome: Saliva proteomics	Microbiome measurements on saliva	2 years
Microbiome: Urine Next Generation Sequencing of microbial DNA	Microbiome measurements on urine	2 years
Microbiome: Saliva Next Generation Sequencing of microbial DNA	Microbiome measurements on saliva	2 years
Microbiome: Feces Next Generation Sequencing of microbial DNA	Microbiome measurements on feces	2 years
Genetics: Whole genome sequencing of blood	Whole genome sequencing of blood	6 years
Genetics: Whole genome sequencing of liver biopsy	Whole genome sequencing of liver biopsy	6 years
Microbiome: Feces Next Generation Sequencing of microbial DNA	Microbiome measurements on feces	6 years
Microbiome: Feces metatranscriptomics	Microbiome measurements on feces	6 years
Microbiome: Feces metabolomics	Microbiome measurements on feces	6 years
Microbiome: Feces proteomics	Microbiome measurements on feces	6 years
Microbiome: Urine Next Generation Sequencing of microbial DNA	Microbiome measurements on urine	6 years
Microbiome: Urine metatranscriptomics	Microbiome measurements on urine	6 years
Microbiome: Urine metabolomics	Microbiome measurements on urine	6 years
Microbiome: Urine proteomics	Microbiome measurements on urine	6 years
Microbiome: Saliva Next Generation Sequencing of microbial DNA	Microbiome measurements on saliva	6 years
Microbiome: Saliva metatranscriptomics	Microbiome measurements on saliva	6 years
Microbiome: Saliva metabolomics	Microbiome measurements on saliva	6 years
Microbiome: Saliva proteomics	Microbiome measurements on saliva	6 years
Genetics: Whole genome sequencing of blood	Whole genome sequencing of blood	11 years
Genetics: Whole genome sequencing of liver biopsy	Whole genome sequencing of liver biopsy	11 years
Microbiome: Feces Next Generation Sequencing of microbial DNA	Microbiome measurements on feces	11 years
Microbiome: Feces metatranscriptomics	Microbiome measurements on feces	11 years
Microbiome: Feces metabolomics	Microbiome measurements on feces	11 years
Microbiome: Feces proteomics	Microbiome measurements on feces	11 years
Microbiome: Urine Next Generation Sequencing of microbial DNA	Microbiome measurements on urine	11 years
Microbiome: Urine metatranscriptomics	Microbiome measurements on urine	11 years
Microbiome: Urine metabolomics	Microbiome measurements on urine	11 years
Microbiome: Urine proteomics	Microbiome measurements on urine	11 years
Microbiome: Saliva Next Generation Sequencing of microbial DNA	Microbiome measurements on saliva	11 years
Microbiome: Saliva metatranscriptomics	Microbiome measurements on saliva	11 years
Microbiome: Saliva metabolomics	Microbiome measurements on saliva	11 years
Microbiome: Saliva proteomics	Microbiome measurements on saliva	11 years
Genetics: Whole genome sequencing of blood	Whole genome sequencing of blood	16 years
Genetics: Whole genome sequencing of liver biopsy	Whole genome sequencing of liver biopsy	16 years
Microbiome: Feces metatranscriptomics	Microbiome measurements on feces	16 years
Microbiome: Feces Next Generation Sequencing of microbial DNA	Microbiome measurements on feces	16 years
Microbiome: Feces metabolomics	Microbiome measurements on feces	16 years
Microbiome: Feces proteomics	Microbiome measurements on feces	16 years
Microbiome: Urine metatranscriptomics	Microbiome measurements on urine	16 years
Microbiome: Urine Next Generation Sequencing of microbial DNA	Microbiome measurements on urine	16 years
Microbiome: Urine metabolomics	Microbiome measurements on urine	16 years
Microbiome: Urine proteomics	Microbiome measurements on urine	16 years
Microbiome: Saliva metatranscriptomics	Microbiome measurements on saliva	16 years
Microbiome: Saliva Next Generation Sequencing of microbial DNA	Microbiome measurements on saliva	16 years
Microbiome: Saliva metabolomics	Microbiome measurements on saliva	16 years
Microbiome: Saliva proteomics	Microbiome measurements on saliva	16 years
Status of the cardiac system: Ultrasound of the heart	% of patients with anatomic anomalies on ultrasound of the heart	Inclusion
Status of the cardiac system: MRI of the lymph system	% of patients with central lymph system anomaly	Inclusion
Status of the cardiac system: Near Infrared Fluorescence of the lymph system	Near Infrared Fluorescence of the lymph system	Inclusion
Status of the cardiac system: Ultrasound of the heart	% of patients with anatomic anomalies on ultrasound of the heart	1 year
Status of the cardiac system: MRI of the lymph system	% of patients with central lymph system anomaly	1 year
Status of the cardiac system: Near Infrared Fluorescence of the lymph system	Near Infrared Fluorescence of the lymph system	1 year
Status of the cardiac system: Ultrasound of the heart	% of patients with anatomic anomalies on ultrasound of the heart	2 years
Status of the cardiac system: MRI of the lymph system	% of patients with central lymph system anomaly	2 years
Status of the cardiac system: Near Infrared Fluorescence of the lymph system	Near Infrared Fluorescence of the lymph system	2 years
Status of the cardiac system: Ultrasound of the heart	% of patients with anatomic anomalies on ultrasound of the heart	6 years
Status of the cardiac system: MRI of the lymph system	% of patients with central lymph system anomaly	6 years
Status of the cardiac system: Near Infrared Fluorescence of the lymph system	Near Infrared Fluorescence of the lymph system	6 years
Status of the cardiac system: Ultrasound of the heart	% of patients with anatomic anomalies on ultrasound of the heart	11 years
Status of the cardiac system: MRI of the lymph system	% of patients with central lymph system anomaly	11 years
Status of the cardiac system: Near Infrared Fluorescence of the lymph system	Near Infrared Fluorescence of the lymph system	11 years
Status of the cardiac system: Ultrasound of the heart	% of patients with anatomic anomalies on ultrasound of the heart	16 years
Status of the cardiac system: MRI of the lymph system	% of patients with central lymph system anomaly	16 years
Status of the cardiac system: Near Infrared Fluorescence of the lymph system	Near Infrared Fluorescence of the lymph system	16 years
Level of Physical activity	Accelerometer measurements	Inclusion
Level of Physical activity	Accelerometer measurements	1 year
Level of Physical activity	Accelerometer measurements	2 years
Level of Physical activity	Accelerometer measurements	6 years
Level of Physical activity	Accelerometer measurements	11 years
Level of Physical activity	Accelerometer measurements	16 years
Ultrasound of liver and bile ducts with elastography	% of patients with liver fibrosis measured with ultrasound	Inclusion
Liver biopsy	Level of liver fibrosis (grade 0-4)	Inclusion
FGF-19; Fibroblast growth factor 19	Liver fibrosis status	Inclusion
ELF-score: Enhanced Liver Fibrosis	Liver fibrosis status	Inclusion
INR: international normalized ratio	Standard liver evaluation	Inclusion
prothrombin+proconvertin (PP)	Standard liver evaluation	Inclusion
ALAT: alanine transaminase	Standard liver evaluation	Inclusion
GGT: Gamma-glutamyl transferase	Standard liver evaluation	Inclusion
Bilirubin	Standard liver evaluation	Inclusion
ASAT: Aspartate transaminase	Standard liver evaluation	Inclusion
Alkaline phosphatase	Standard liver evaluation	Inclusion
Ammonia	Standard liver evaluation	Inclusion
Thrombocytes	Standard liver evaluation	Inclusion
Ultrasound of liver and bile ducts with elastography	% of patients with liver fibrosis measured with ultrasound	1 year
FGF-19: Fibroblast growth factor 19	Liver fibrosis status	1 year
ELF-score: Enhanced Liver Fibrosis	Liver fibrosis status	1 year
INR: international normalized ratio	Standard liver evaluation	1 year
prothrombin+proconvertin (PP)	Standard liver evaluation	1 year
ALAT: alanine transaminase	Standard liver evaluation	1 year
ASAT: Aspartate transaminase	Standard liver evaluation	1 year
GGT: Gamma-glutamyl transferase	Standard liver evaluation	1 year
Bilirubin	Standard liver evaluation	1 year
Alkaline phosphatase	Standard liver evaluation	1 year
Ammonia	Standard liver evaluation	1 year
Thrombocytes	Standard liver evaluation	1 year
Liver biopsy	Level of liver fibrosis (grade 0-4)	1 year
Ultrasound of liver and bile ducts with elastography	% of patients with liver fibrosis measured with ultrasound	2 years
FGF-19: Fibroblast growth factor 19	Liver fibrosis status	2 years
ELF-score: Enhanced Liver Fibrosis	Liver fibrosis status	2 years
Liver biopsy	Level of liver fibrosis (grade 0-4)	2 years
INR: international normalized ratio	Standard liver evaluation	2 years
prothrombin+proconvertin (PP)	Standard liver evaluation	2 years
ALAT: alanine transaminase	Standard liver evaluation	2 years
ASAT: Aspartate transaminase	Standard liver evaluation	2 years
GGT: Gamma-glutamyl transferase	Standard liver evaluation	2 years
Alkaline phosphatase	Standard liver evaluation	2 years
Bilirubin	Standard liver evaluation	2 years
Ammonia	Standard liver evaluation	2 years
Thrombocytes	Standard liver evaluation	2 years
Ultrasound of liver and bile ducts with elastography	% of patients with liver fibrosis measured with ultrasound	6 years
Liver biopsy	Level of liver fibrosis (grade 0-4)	6 years
ELF-score: Enhanced Liver Fibrosis	Liver fibrosis status	6 years
FGF-19: Fibroblast growth factor 19	Liver fibrosis status	6 years
INR: international normalized ratio	Standard liver evaluation	6 years
prothrombin+proconvertin (PP)	Standard liver evaluation	6 years
ALAT: alanine transaminase	Standard liver evaluation	6 years
ASAT: Aspartate transaminase	Standard liver evaluation	6 years
GGT: Gamma-glutamyl transferase	Standard liver evaluation	6 years
Bilirubin	Standard liver evaluation	6 years
Alkaline phosphatase	Standard liver evaluation	6 years
Ammonia	Standard liver evaluation	6 years
Thrombocytes	Standard liver evaluation	6 years
Ultrasound of liver and bile ducts with elastography	% of patients with liver fibrosis measured with ultrasound	11 years
Liver biopsy	Level of liver fibrosis (grade 0-4)	11 years
FGF-19: Fibroblast growth factor 19	Liver fibrosis status	11 years
ELF-score: Enhanced Liver Fibrosis	Liver fibrosis status	11 years
INR: international normalized ratio	Standard liver evaluation	11 years
prothrombin+proconvertin (PP)	Standard liver evaluation	11 years
ALAT: alanine transaminase	Standard liver evaluation	11 years
ASAT: Aspartate transaminase	Standard liver evaluation	11 years
GGT: Gamma-glutamyl transferase	Standard liver evaluation	11 years
Bilirubin	Standard liver evaluation	11 years
Alkaline phosphatase	Standard liver evaluation	11 years
Ammonia	Standard liver evaluation	11 years
Thrombocytes	Standard liver evaluation	11 years
Ultrasound of liver and bile ducts with elastography	% of patients with liver fibrosis measured with ultrasound	16 years
Liver biopsy	Level of liver fibrosis (grade 0-4)	16 years
FGF-19: Fibroblast growth factor 19	Liver fibrosis status	16 years
ELF-score: Enhanced Liver Fibrosis	Liver fibrosis status	16 years
INR: international normalized ratio	Standard liver evaluation	16 years
prothrombin+proconvertin (PP)	Standard liver evaluation	16 years
ALAT: alanine transaminase	Standard liver evaluation	16 years
ASAT: Aspartate transaminase	Standard liver evaluation	16 years
GGT: Gamma-glutamyl transferase	Standard liver evaluation	16 years
Bilirubin	Standard liver evaluation	16 years
Alkaline phosphatase	Standard liver evaluation	16 years
Ammonia	Standard liver evaluation	16 years
Thrombocytes	Standard liver evaluation	16 years
Clinical examination: Cirrhosis stigmata	Incidence of spider angioma	Inclusion
Clinical examination: Cirrhosis stigmata	Incidence of spider angioma	1 year
Clinical examination: Cirrhosis stigmata	Incidence of spider angioma	2 years
Clinical examination: Cirrhosis stigmata	Incidence of spider angioma	6 years
Clinical examination: Cirrhosis stigmata	Incidence of spider angioma	11 years
Clinical examination: Cirrhosis stigmata	Incidence of spider angioma	16 years
Clinical examination: Cirrhosis stigmata	Incidence of ascitis	Inclusion
Clinical examination: Cirrhosis stigmata	Incidence of ascitis	1 year
Clinical examination: Cirrhosis stigmata	Incidence of ascitis	2 years
Clinical examination: Cirrhosis stigmata	Incidence of ascitis	6 years
Clinical examination: Cirrhosis stigmata	Incidence of ascitis	11 years
Clinical examination: Cirrhosis stigmata	Incidence of ascitis	16 years
Clinical examination: Cirrhosis stigmata	Incidence of palmar erythema	Inclusion
Clinical examination: Cirrhosis stigmata	Incidence of palmar erythema	1 year
Clinical examination: Cirrhosis stigmata	Incidence of palmar erythema	2 years
Clinical examination: Cirrhosis stigmata	Incidence of palmar erythema	6 years
Clinical examination: Cirrhosis stigmata	Incidence of palmar erythema	11 years
Clinical examination: Cirrhosis stigmata	Incidence of palmar erythema	16 years
Anthropometry: Length	cm	Inclusion
Anthropometry: Length	cm	1 year
Anthropometry: Length	cm	2 years
Anthropometry: Height	cm	6 years
Anthropometry: Height	cm	11 years
Anthropometry: Height	cm	16 years
Anthropometry: Weight	kg	Inclusion
Anthropometry: Weight	kg	1 year
Anthropometry: Weight	kg	2 years
Anthropometry: Weight	kg	6 years
Anthropometry: Weight	kg	11 years
Anthropometry: Weight	kg	16 years
Anthropometry: Mid-upper arm circumference (MUAC)	mm	Inclusion
Anthropometry: Mid-upper arm circumference (MUAC)	mm	1 year
Anthropometry: Mid-upper arm circumference (MUAC)	mm	2 years
Anthropometry: Mid-upper arm circumference (MUAC)	mm	6 years
Anthropometry: Mid-upper arm circumference (MUAC)	mm	11 years
Anthropometry: Mid-upper arm circumference (MUAC)	mm	16 years
Anthropometry: Head circumference	cm	Inclusion
Anthropometry: Head circumference	cm	1 year
Anthropometry: Head circumference	cm	2 years
Anthropometry: Head circumference	cm	6 years
Anthropometry: Head circumference	cm	11 years
Anthropometry: Head circumference	cm	16 years
Essential fatty acids		Inclusion
Essential fatty acids		1 year
Essential fatty acids		2 years
Essential fatty acids		6 years
Essential fatty acids		11 years
Essential fatty acids		16 years
IGF-1	Insulin-like growth factor 1	Inclusion
IGF-1	Insulin-like growth factor 1	1 year
IGF-1	Insulin-like growth factor 1	2 years
IGF-1	Insulin-like growth factor 1	6 years
IGF-1	Insulin-like growth factor 1	11 years
IGF-1	Insulin-like growth factor 1	16 years
Meal stimulation measuring incretin		Inclusion
Meal stimulation measuring incretin		1 year
Meal stimulation measuring incretin		2 years
Meal stimulation measuring incretin		6 years
Meal stimulation measuring incretin		11 years
Meal stimulation measuring incretin		16 years
Bile acid		Inclusion
Bile acid		1 year
Bile acid		2 years
Bile acid		6 years
Bile acid		11 years
Bile acid		16 years
Autotaxin		Inclusion
Autotaxin		1 year
Autotaxin		2 years
Autotaxin		6 years
Autotaxin		11 years
Autotaxin		16 years
EDTA clearance	Glomerular Filtration Rate Measured by 51 Cr-EDTA Clearance	Inclusion
EDTA clearance	Glomerular Filtration Rate Measured by 51 Cr-EDTA Clearance	1 year
EDTA clearance	Glomerular Filtration Rate Measured by 51 Cr-EDTA Clearance	2 years
EDTA clearance	Glomerular Filtration Rate Measured by 51 Cr-EDTA Clearance	6 years
EDTA clearance	Glomerular Filtration Rate Measured by 51 Cr-EDTA Clearance	11 years
EDTA clearance	Glomerular Filtration Rate Measured by 51 Cr-EDTA Clearance	16 years
Vaccination status	Level of antibodies	Inclusion
Vaccination status	Level of antibodies	1 year
Vaccination status	Level of antibodies	2 years
Vaccination status	Level of antibodies	6 years
Vaccination status	Level of antibodies	11 years
Vaccination status	Level of antibodies	16 years
Immunoresponse: RTE	Recent thymic emigrants	Inclusion
Immunoresponse: RTE	Recent thymic emigrants	1 year
Immunoresponse: RTE	Recent thymic emigrants	2 years
Immunoresponse: RTE	Recent thymic emigrants	6 years
Immunoresponse: RTE	Recent thymic emigrants	11 years
Immunoresponse: RTE	Recent thymic emigrants	16 years
Immunoresponse: Flow panel	T-cell differentiation	Inclusion
Immunoresponse: Flow panel	T-cell differentiation	1 year
Immunoresponse: Flow panel	T-cell differentiation	2 years
Immunoresponse: Flow panel	T-cell differentiation	6 years
Immunoresponse: Flow panel	T-cell differentiation	11 years
Immunoresponse: Flow panel	T-cell differentiation	16 years
Immunoresponse: Immunoglobulin		Inclusion
Immunoresponse: Immunoglobulin		1 year
Immunoresponse: Immunoglobulin		2 years
Immunoresponse: Immunoglobulin		6 years
Immunoresponse: Immunoglobulin		11 years
Immunoresponse: Immunoglobulin		16 years
Immunoresponse: Somatic hyper mutation		Inclusion
Immunoresponse: Somatic hyper mutation		1 year
Immunoresponse: Somatic hyper mutation		2 years
Immunoresponse: Somatic hyper mutation		6 years
Immunoresponse: Somatic hyper mutation		11 years
Immunoresponse: Somatic hyper mutation		16 years
Epstein-Barr Virus (EBV)	level of EBV DNA present	Inclusion
Epstein-Barr Virus (EBV)	level of EBV DNA present	1 year
Epstein-Barr Virus (EBV)	level of EBV DNA present	2 years
Epstein-Barr Virus (EBV)	level of EBV DNA present	6 years
Epstein-Barr Virus (EBV)	level of EBV DNA present	11 years
Epstein-Barr Virus (EBV)	level of EBV DNA present	16 years
Cytomegalovirus (CMV)	level of CMV DNA present	Inclusion
Cytomegalovirus (CMV)	level of CMV DNA present	1 year
Cytomegalovirus (CMV)	level of CMV DNA present	2 years
Cytomegalovirus (CMV)	level of CMV DNA present	6 years
Cytomegalovirus (CMV)	level of CMV DNA present	11 years
Cytomegalovirus (CMV)	level of CMV DNA present	16 years
Hepatobiliary scintigraphy	Hepatic extraction fraction	Inclusion
Hepatobiliary scintigraphy	Hepatic extraction fraction	1 year
Hepatobiliary scintigraphy	Hepatic extraction fraction	2 years
Hepatobiliary scintigraphy	Hepatic extraction fraction	6 years
Hepatobiliary scintigraphy	Hepatic extraction fraction	11 years
Hepatobiliary scintigraphy	Hepatic extraction fraction	16 years
MRI of liver and bile ducts with elastography	Liver stiffness	Inclusion
MRI of liver and bile ducts with elastography	Liver stiffness	1 year
MRI of liver and bile ducts with elastography	Liver stiffness	2 years
MRI of liver and bile ducts with elastography	Liver stiffness	6 years
MRI of liver and bile ducts with elastography	Liver stiffness	11 years
MRI of liver and bile ducts with elastography	Liver stiffness	16 years
Fibroscan	Liver stiffness (number)	Inclusion
Fibroscan	Liver stiffness (number)	1 year
Fibroscan	Liver stiffness (number)	2 years
Fibroscan	Liver stiffness (number)	6 years
Fibroscan	Liver stiffness (number)	11 years
Fibroscan	Liver stiffness (number)	16 years
Indocyanine green clearance		Inclusion
Indocyanine green clearance		1 year
Indocyanine green clearance		2 years
Indocyanine green clearance		6 years
Indocyanine green clearance		11 years
Indocyanine green clearance		16 years
Fecal fat measurements		Inclusion
Fecal fat measurements		1 year
Fecal fat measurements		2 years
Fecal fat measurements		6 years
Fecal fat measurements		11 years
Fecal fat measurements		16 years
Thymus scan with ultrasound	Thymic index (measurement of size)	Inclusion
Thymus scan with ultrasound	Thymic index (measurement of size)	1 year
Thymus scan with ultrasound	Thymic index (measurement of size)	2 years
Thymus scan with ultrasound	Thymic index (measurement of size)	6 years
Thymus scan with ultrasound	Thymic index (measurement of size)	11 years
Thymus scan with ultrasound	Thymic index (measurement of size)	16 years
DEXA scan	Dual energy x-ray absorptiometry	Inclusion
DEXA scan	Dual energy x-ray absorptiometry	1 year
DEXA scan	Dual energy x-ray absorptiometry	2 years
DEXA scan	Dual energy x-ray absorptiometry	6 years
DEXA scan	Dual energy x-ray absorptiometry	11 years
DEXA scan	Dual energy x-ray absorptiometry	16 years
PEDS-QL	Pediatric Quality of Life Inventory Higher scores indicate better quality of life, from 0-100	Inclusion
PEDS-QL	Pediatric Quality of Life Inventory Higher scores indicate better quality of life, from 0-100	1 year
PEDS-QL	Pediatric Quality of Life Inventory Higher scores indicate better quality of life, from 0-100	2 years
PEDS-QL	Pediatric Quality of Life Inventory Higher scores indicate better quality of life, from 0-100	6 years
PEDS-QL	Pediatric Quality of Life Inventory Higher scores indicate better quality of life, from 0-100	11 years
PEDS-QL	Pediatric Quality of Life Inventory Higher scores indicate better quality of life, from 0-100	16 years
Leptin		Inclusion
Leptin		1 year
Leptin		2 years
Leptin		6 years
Leptin		11 years
Leptin		16 years

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark
• Investigators: Principal Investigator: Vibeke Brix Christensen, MD, PhD, DMSc, Rigshospitalet, Denmark

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 1, 2020
• Primary Completion (ANTICIPATED): December 31, 2039
• Study Completion (ANTICIPATED): December 31, 2040

Study Registration Dates

• First Submitted: March 8, 2022
• First Submitted That Met QC Criteria: May 30, 2022
• First Posted (ACTUAL): June 1, 2022

Study Record Updates

• Last Update Posted (ACTUAL): June 1, 2022
• Last Update Submitted That Met QC Criteria: May 30, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Congenital Abnormalities; Biliary Tract Diseases; Bile Duct Diseases; Digestive System Abnormalities; Liver Diseases; Biliary Atresia
• Other Study ID Numbers: H-19042934

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No allowed from Danish government

Drug and device information, study documents

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