Genetics of Fatty Liver Disease in Children

Yale University

Status: Completed

Conditions: Non Alcoholic Fatty Liver Disease

Treatments: Other: genotyping; Other: liver biopsy; Other: stool sample; Other: ogtt; Other: abdominal and liver magnetic resonance imaging

Study type: Observational

Funder types: Other; NIH

Identifiers

NCT01966627

R01HD040787 (U.S. NIH Grant/Contract)

1104008388

Details and patient eligibility

About

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.

Full 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.

Enrollment: 381 patients

Sex: All

Ages: 7 to 18 years old

Volunteers: No Healthy Volunteers

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.

Trial design

381 participants in 1 patient group

Pediatric NAFLD Cohort

Description:

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.

Treatment:

Other: genotyping

Other: stool sample

Other: ogtt

Other: liver biopsy

Other: abdominal and liver magnetic resonance imaging