Genetics of Fatty Liver Disease in Children

Completed

• Conditions: Non Alcoholic Fatty Liver Disease
• Interventions: Other: ogtt; Other: genotyping; Other: abdominal and liver magnetic resonance imaging; Other: stool sample; Other: liver biopsy

• Registration Number: NCT01966627
• Lead Sponsor: Yale University

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.

Study Timeline

• Study Start: 2011-07
• Study First Submitted: 2013-07-15
• Study First Submitted QC: 2013-10-16
• Study First Posted: 2013-10-21
• Primary Completion: 2017-07
• Study Completion: 2017-07
• Status Verified: 2017-12
• Last Update Submitted: 2017-12-06
• Last Update Posted: 2017-12-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 381

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.

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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.

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Pediatric NAFLD Cohort	ogtt	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.
Pediatric NAFLD Cohort	genotyping	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.
Pediatric NAFLD Cohort	stool sample	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.
Pediatric NAFLD Cohort	abdominal and liver magnetic resonance imaging	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.
Pediatric NAFLD Cohort	liver biopsy	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.

Primary Outcome Measures

Name	Time	Method
gene expression	Baseline	gene mutation allele variation identification measure via gene extraction

Secondary Outcome Measures

Name	Time	Method
glucose tolerance	2 years	glucose tolerance status measured by 3 hour oral glucose tolerance test done at baseline and 2 year follow up
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

Trial Locations

Locations (1)

Yale University; 🇺🇸 New Haven, Connecticut, United States