Genetics of Fatty Liver Disease in Children

Study Overview
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Brief Summary
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This is a study to investigate genetic predisposition to hepatic steatosis and the expression of gluconeogenic and lipogenic genes in livers of obese children and adolescents. Hypothesis 1: Common variants recently associated with variation in plasma TG levels identified in Genome Wide Association Studies (GWAS) (such as GCKR, PNPLA3) can affect accumulation of fat and subsequent development of Non Alcoholic Fatty Liver Disease (NAFLD). Gene variants act in additive or synergistic manner with progressive liver fat accumulation per additional risk allele. Hypothesis 2: With increase in hepatic fat content NASH and fibrosis will increase. Furthermore, expression of lipogenic markers (SREBP1c) will increase.

Detailed Description
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To establish a cohort of obese youths to prospectively analyze potential factors (genetic and nutritional factors) that might affect the expression and progression of NAFLD. This study will determine genetic markers and their ability to convey susceptibility to NAFLD in obese children and adolescents. Furthermore, potential mechanisms that might contribute to the accumulation of hepatic Triglyceride (TG) accumulation will be, for the first time, assessed by genotyping. Additionally, we will examine the presence of intestinal microbiome in the development of fatty liver through stool collection.

Official Title
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Genetics of Fatty Liver Disease in Childhood Obesity.

Conditions
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Non Alcoholic Fatty Liver Disease

Intervention / Treatment
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* Other: ogtt
* Other: genotyping
* Other: abdominal and liver magnetic resonance imaging
* Other: stool sample
* Other: liver biopsy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: between 7 and 18 years of age, overweight or obese with a BMI greater than the 85th percentile for age and gender, and be otherwise healthy. Exclusion Criteria: the use of any medication that alters liver function, blood pressure, glucose or lipid metabolism and no use of any antipsychotic medication Youth on chronic anti-inflammatory medications or who consume alcohol are also excluded.

Ages Eligible for Study
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Minimum Age: 7 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Pediatric NAFLD Cohort<br>Overweight and obese children and adolescents at risk for non alcoholic fatty liver disease will undergo oral glucose tolerance testing (ogtt), genotyping, abdominal and liver magnetic resonance imaging (mri), and will provide a stool sample at baseline and at 2 year follow up. A small subset will undergo liver biopsy to test for hepatic steatosis and nonalcoholic steatohepatitis. | Other: ogtt<br>* oral glucose tolerance test<br>Other: genotyping<br>* genotyping to look for risk alleles<br>Other: abdominal and liver magnetic resonance imaging<br>* magnetic resonance imaging scan of abdomen and liver - abdominal and liver mri<br>Other: stool sample<br>* stool sample taken to investigate metabolites<br>Other: liver biopsy<br>* liver biopsy to examine for cellular change and steatosis<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| gene expression | gene mutation allele variation identification measure via gene extraction | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| hepatic fat content | Abdominal MRI to measure liver fat and subcutaneous and visceral fat ratio done at baseline and 2 year follow up | 2 years | 
| glucose tolerance | glucose tolerance status measured by 3 hour oral glucose tolerance test done at baseline and 2 year follow up | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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non alcoholic fatty liver, childhood obesity, genetic variants