Utilizing Non-Invasive Fibroscan® Technology to Identify Genetic Markers for Fatty Liver Progression
Condition: Non-alcoholic Fatty Liver Disease
MeSH terms: Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
Study type: Observational

Summary: 
      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.
    

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.
    

Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Residents of the greater Charlotte, NC metropolitan area
      
Biospecimen description: 
      Whole blood will be collected and used for DNA extraction. Plasma and serum will also be
      collected and banked.
    
Keywords: Non-alcoholic fatty liver disease; Fatty liver; Steatosis; Fibrosis; Liver Stiffness; Cirrhosis; Genetics; Single Nucleotide Polymorphism