Utilizing Non-Invasive Fibroscan® Technology to Identify Genetic Markers for Fatty Liver Progression

Non-alcoholic fatty liver disease (NAFLD) is a common disorder, affecting ~30% of people in the general population and up to 96% of obese individuals. Variations in several genes have been found to be associated with fatty liver, but these associations only explain a small percentage of the risk, and further studies are needed. In many cases NAFLD does not cause serious side effects, but in some individuals it progresses to scarring or hardening of the liver, liver failure, and cancer.

The purpose of this research study is to determine if individuals who carry certain genetic variations in a gene related to bile and choline metabolism have an increased risk of fatty liver progressing to fibrosis, or scarring of the liver. This study will also use a new, non-invasive method called the FibroScan® to measure liver fat and liver stiffness. The FibroScan® device is FDA approved for use to measure liver stiffness, but not for the liver fat measurement. However, the FibroScan® instrument is considered a non-significant risk device. Since its induction in Europe and worldwide in 2003, there have been no adverse effects reported with this device.

Study Overview

• Status: Completed
• Conditions: Non-alcoholic Fatty Liver Disease

Detailed Description

Purpose: ABCB4 is a gene that intersects choline and bile metabolism, two processes that are highly relevant for liver disease. The investigators have identified a pattern of genetic variation that is associated with fatty liver burden and potentially, risk for liver disease. One of the most prominent genes in this pattern is ABCB4. This data needs to be replicated in the general population. This study will test the hypothesis that aberrant function of ABCB4 due to genetic variations will increase the risk of fatty liver progression to fibrosis. It will also implement innovative, non-invasive technology to measure liver fat and fibrosis utilizing the FibroScan® instrument. As additional proof of principle that the measurements we are making correlate with genetics, the investigators will also measure two genetic variants that have been shown in many studies to correlate with liver fat and fibrosis by their research team and others: PNPLA3 rs738409 and rs2281135. Finally, the investigators will calculate a NAFLD-Fibrosis score as an additional correlate to liver disease status.

Participants: To test this hypothesis, 50 ethnically diverse, overweight or obese male and female adults will be recruited from the general population.

Procedures: Genotyping to correlate variation in the ABCB4 and PNPLA3 genes with level of fatty liver and progression to fibrosis with the FibroScan®. Calculation of NAFLD-Fibrosis score.

• Study Type: Observational
• Enrollment (Actual): 53

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Kannapolis, North Carolina, United States, 28081
      • UNC Nutrition Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Residents of the greater Charlotte, NC metropolitan area

Description

Inclusion Criteria:

• Males and females
• Ages 18-70 years
• Body mass index 25-45

Exclusion Criteria:

• Alcohol consumption > 20 grams/day
• Liver disease from a cause other than NAFLD (such as hepatitis B/C, alcoholic liver disease, or autoimmune hepatitis)
• Pharmacological therapy for liver disease
• History of liver transplant
• Presence of implantable medical devices
• Ascites
• Pregnancy
• Smoking or use of recreational drugs

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Liver stiffness measurement via transient elastography	Measured by FibroScan® instrument	Study Day 1
Liver fat measurement via Controlled Attenuation Parameter	Measured using FibroScan® instrument	Study Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NAFLD-Fibrosis score	This is a calculated score which is a good predictor of liver disease	Study Day 1

Collaborators and Investigators

• Sponsor: UNC Nutrition Research Institute

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: September 22, 2014
• First Submitted That Met QC Criteria: October 14, 2014
• First Posted (Estimate): October 17, 2014

Study Record Updates

• Last Update Posted (Estimate): January 16, 2015
• Last Update Submitted That Met QC Criteria: January 15, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Keywords: Fibrosis; Genetics; Non-alcoholic fatty liver disease; Steatosis; Cirrhosis; Fatty liver; Single Nucleotide Polymorphism; Liver Stiffness
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: 13-1392