Biliary Atresia, Cognitive Impairment
Conditions
Brief 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
Interventions
OTHERNeurocognitive monitoring
Neurocognitive tests and MRI of the brain
Sponsors
Rigshospitalet, Denmark
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
0 Years to 18 Years
Healthy volunteers
Yes
Inclusion criteria
* Biliary atresia * Tetralogy of Fallot * Healthy controls
Exclusion criteria
\- Not able to participate in exams
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Neurocognitive status: BADS-C | Inclusion | 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 |
| MRI of the brain | Inclusion | % of patients with anatomic anomalies on MRI of the brain |
| Neurocognitive status: Early movement repertoire (General movement) | Inclusion | 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. |
| Neurocognitive status: Alberta Infant Motor Scale | Inclusion | Neurocognitive test panel depending on age at inclusion: Alberta Infant Motor Scale if inclusion at diagnosis Percentile, highest is the best |
| Neurocognitive status: Bayley Scales of Development III | Inclusion | 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 |
| Neurocognitive status: WIPPSI | Inclusion | 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 |
| Neurocognitive status: ABC Movement | Inclusion | 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 |
| Neurocognitive status: WISC-IV | Inclusion | 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 |
| Neurocognitive status: Auditory Verbal Learning Test/ToMaL | Inclusion | 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 |
| Neurocognitive status: TEA-Ch | Inclusion | 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 |
| Neurocognitive status: Test of Visual Perceptual Skills | Inclusion | Neurocognitive test panel depending on age at inclusion: Test of Visual Perceptual Skills if inclusion between 6-18 years Percentile, highest is best |
| Neurocognitive status: CANTAB | Inclusion | Neurocognitive test panel depending on age at inclusion: CANTAB if inclusion between 6-18 years Cambridge Neuropsychological Test Automated Battery |
| Neurocognitive status: The Beery Visuo-Motor Integration test | Inclusion | 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 |
| Neurocognitive status: WAIS IV | Inclusion | 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 |
| Neurocognitive status: Kiddie-sads | Inclusion | 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 |
| Neurocognitive status: BRIEF 1 | Inclusion | 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 |
| Neurocognitive status: BRIEF 2 | Inclusion | 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 |
| Neurocognitive status: CBCL | Inclusion | Neurocognitive test panel depending on age at inclusion: CBCL if included between 2-18 years Child Behavior Checklist, percentile, lowest is best |
| Neurocognitive status: ADHD screening | Inclusion | Neurocognitive test panel depending on age at inclusion: ADHD screening if included between 2-18 years Lowest is best, 0-78 |
| Neurocognitive status: SRS-2 | Inclusion | 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 |
| Neurocognitive status: Vineland | Inclusion | 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 |
| Neurocognitive status: Kiddie-Sads | 1 year | Kiddie-Sads Kiddie Schedule for Affective Disorders and Schizophrenia, 0-61, lowest is best |
| Neurocognitive status: ADHD | 2 years | ADHD Lowest is best, 0-78 |
| Neurocognitive: Movement ABC | 6 years | Neurocognitive test panel depending on age Movement Assessment Battery for Children, mean 10 SD 3, highest is best |
| Neurocognitive status: Movement ABC | 11 years | 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 |
| Neurocognitive status:TEA-Ch | 11 years | TEA-Ch Test of Everyday Attention for Children, normalized to z-score, highest is best |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Bilirubin | Inclusion | Standard liver evaluation |
| ASAT: Aspartate transaminase | Inclusion | Standard liver evaluation |
| Alkaline phosphatase | Inclusion | Standard liver evaluation |
| Ammonia | Inclusion | Standard liver evaluation |
| Thrombocytes | Inclusion | Standard liver evaluation |
| FGF-19: Fibroblast growth factor 19 | 1 year | Liver fibrosis status |
| Clinical examination: Cirrhosis stigmata | Inclusion | Incidence of spider angioma |
| Anthropometry: Length | Inclusion | cm |
| Anthropometry: Height | 6 years | cm |
| Anthropometry: Weight | Inclusion | kg |
| Anthropometry: Mid-upper arm circumference (MUAC) | Inclusion | mm |
| Anthropometry: Head circumference | Inclusion | cm |
| Essential fatty acids | Inclusion | — |
| IGF-1 | Inclusion | Insulin-like growth factor 1 |
| Meal stimulation measuring incretin | Inclusion | — |
| Bile acid | Inclusion | — |
| Autotaxin | Inclusion | — |
| EDTA clearance | Inclusion | Glomerular Filtration Rate Measured by 51 Cr-EDTA Clearance |
| Vaccination status | Inclusion | Level of antibodies |
| Immunoresponse: RTE | Inclusion | Recent thymic emigrants |
| Immunoresponse: Flow panel | Inclusion | T-cell differentiation |
| Immunoresponse: Immunoglobulin | Inclusion | — |
| Immunoresponse: Somatic hyper mutation | Inclusion | — |
| Epstein-Barr Virus (EBV) | Inclusion | level of EBV DNA present |
| Cytomegalovirus (CMV) | Inclusion | level of CMV DNA present |
| Hepatobiliary scintigraphy | Inclusion | Hepatic extraction fraction |
| MRI of liver and bile ducts with elastography | Inclusion | Liver stiffness |
| Genetics: Whole genome sequencing of blood | Inclusion | Whole genome sequencing of blood |
| Indocyanine green clearance | Inclusion | — |
| Fecal fat measurements | Inclusion | — |
| Thymus scan with ultrasound | Inclusion | Thymic index (measurement of size) |
| DEXA scan | Inclusion | Dual energy x-ray absorptiometry |
| PEDS-QL | Inclusion | Pediatric Quality of Life Inventory Higher scores indicate better quality of life, from 0-100 |
| Leptin | Inclusion | — |
| Fibroscan | Inclusion | Liver stiffness (number) |
| Genetics: Whole genome sequencing of liver biopsy | Inclusion | Whole genome sequencing of liver biopsy |
| Microbiome: Urine proteomics | Inclusion | Microbiome measurements on urine |
| Microbiome: Feces proteomics | Inclusion | Microbiome measurements on feces |
| Microbiome: Saliva proteomics | Inclusion | Microbiome measurements on saliva |
| Microbiome: Feces Next Generation Sequencing of microbial DNA | Inclusion | Microbiome measurement on feces |
| Microbiome: Urine Next Generation Sequencing of microbial DNA | Inclusion | Microbiome measurement on urine |
| Microbiome: Saliva Next Generation Sequencing of microbial DNA | Inclusion | Microbiome measurement on saliva |
| Microbiome: Feces metabolomics | Inclusion | Microbiome measurements on feces |
| Microbiome: Urine metabolomics | Inclusion | Microbiome measurements on urine |
| Microbiome: Saliva metabolomics | Inclusion | Microbiome measurements on saliva |
| Microbiome: Feces metatranscriptomics | Inclusion | Microbiome measurements on feces |
| Microbiome: Urine metatranscriptomics | Inclusion | Microbiome measurements on urine |
| Microbiome: Saliva metatranscriptomics | Inclusion | Microbiome measurements on saliva |
| Status of the cardiac system: Ultrasound of the heart | Inclusion | % of patients with anatomic anomalies on ultrasound of the heart |
| Status of the cardiac system: MRI of the lymph system | Inclusion | % of patients with central lymph system anomaly |
| Status of the cardiac system: Near Infrared Fluorescence of the lymph system | Inclusion | Near Infrared Fluorescence of the lymph system |
| Level of Physical activity | Inclusion | Accelerometer measurements |
| Ultrasound of liver and bile ducts with elastography | Inclusion | % of patients with liver fibrosis measured with ultrasound |
| Liver biopsy | Inclusion | Level of liver fibrosis (grade 0-4) |
| FGF-19; Fibroblast growth factor 19 | Inclusion | Liver fibrosis status |
| ELF-score: Enhanced Liver Fibrosis | Inclusion | Liver fibrosis status |
| INR: international normalized ratio | Inclusion | Standard liver evaluation |
| prothrombin+proconvertin (PP) | Inclusion | Standard liver evaluation |
| ALAT: alanine transaminase | Inclusion | Standard liver evaluation |
| GGT: Gamma-glutamyl transferase | Inclusion | Standard liver evaluation |
Countries
Denmark
Contacts
Primary ContactVibeke Brix Christensen, MD, PhD, DMSc
Outcome results
None listed