Non Alcoholic Fatty Liver Disease
Conditions
Keywords
non alcoholic fatty liver, childhood obesity, genetic variants
Brief summary
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
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.
Interventions
OTHERogtt
oral glucose tolerance test
OTHERgenotyping
genotyping to look for risk alleles
OTHERabdominal and liver magnetic resonance imaging
magnetic resonance imaging scan of abdomen and liver - abdominal and liver mri
OTHERstool sample
stool sample taken to investigate metabolites
OTHERliver biopsy
liver biopsy to examine for cellular change and steatosis
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Yale University
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
7 Years to 18 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| gene expression | Baseline | gene mutation allele variation identification measure via gene extraction |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| hepatic fat content | 2 years | Abdominal MRI to measure liver fat and subcutaneous and visceral fat ratio done at baseline and 2 year follow up |
| glucose tolerance | 2 years | glucose tolerance status measured by 3 hour oral glucose tolerance test done at baseline and 2 year follow up |
Other
| Measure | Time frame | Description |
|---|---|---|
| DNA gene sequencing of intestinal bacteria's | 2 years | Measure microbiota diversity via stool samples to understand variance of triglycerides accumulation in liver |
| Use liver biopsy specimen to assess differences in gene expression, as well as inflammation. | As indicated by Pediatric Hepatolgist | liver biopsy tissue obtained when subject is scheduled for pre-ordered biopsy by hepatologist |
Countries
United States
Outcome results
None listed