The Prevalence of Nonalcoholic Fatty Liver Disease (NAFLD) in Adults

NCT03142867 | Terminated

• 1 other identifier: 20513
• Study Type: observational
• Target: 826
• Locations: 1 country
• Sites: 1

Brief Summary

Nonalcoholic fatty liver disease (NAFLD) is a global health concern with a suspected increasing prevalence due to the rise in obesity and diabetes mellitus. The vast majority of patients will have isolated steatosis or steatosis with mild inflammation that is very unlikely to progress in severity. However, about 25% of patients with NAFLD have non-alcoholic steatohepatitis (NASH), the more aggressive form of the disease that is associated with fibrosis progression and potential risk for cirrhosis and end-stage liver disease complications. Additionally, multiple studies have demonstrated an association between NAFLD and the presence of coronary artery disease by either coronary CT angiography (CCTA) or coronary artery calcium (CAC) score. Cardiovascular disease is the most important cause of mortality in patients with the entire spectrum of NAFLD. In the era of advanced imaging and functional vascular assessment it is possible that novel risk assessments are poised to refine overall prognostic estimation in this population. Multiple analyses have suggested that NAFLD is an independent and strong predictor of significant CAD independent of cardiovascular risk factors, including a significant burden of high risk CCTA findings in one analysis of symptomatic patients in the emergency department. Given the multiple metabolic derangements inherent in the NAFLD population, endothelial dysfunction is also an important contributor to global cardiovascular dysfunction. Furthermore, data suggests that patients with NAFLD may be at increased risk of adenomatous polyp formation and colorectal adenocarcinoma. In addition, it is suboptimal to require a liver biopsy to diagnose NASH. Recent imaging advances have made it possible to assess liver fibrosis but have yet to be fully studied in NAFLD. The purpose of this study is to assess the current prevalence and severity of NAFLD in adult subjects. Secondary endpoints include correlation to new vascular function (cine scan of the abdominal aorta) and echocardiographic imaging modalities available at BAMC and to circulating biomarker panels as well as to determine the prevalence and severity of CAD by multidetector coronary CT angiography with subject outcomes being monitored prospectively. Additionally, correlation of NAFLD diagnosis to colonoscopy findings will be performed.

Conditions

Non-Alcoholic Fatty Liver Disease; Non Alcoholic Steatohepatitis

Keywords

Non-Alcoholic Fatty Liver Disease; Non Alcoholic Steatohepatitis; Prevalence; Coronary Artery Disease; PDFF

Outcome Measures

Primary Outcomes (2)

• Prevalence of NAFLD

  Determine the prevalence of NAFLD in military beneficiaries between ages 18 to 80. This will be determined by the % of subjects determined to have NAFLD via liver biopsy.

  from the date of consent to the completion of phase I (up to 3 months)

• Prevalence of NASH

  Determine the prevalence of NASH in military beneficiaries between ages 18 to 80. This will be determined by the % of subjects determined to have NASH via liver biopsy.

  from the date of consent to the completion of phase I (up to 3 months)

Secondary Outcomes (8)

• proton density fat fraction

  Determined at the date of MRI (1 day)

• Liver stiffness measure by Fibroscan

  Determined at the date of Fibroscan (1 day)

• Liver stiffness measure by MRE

  Determined at the date of MRE (1 day)

• Stages of fibrosis and grades of steatosis

  determined at the date of liver biopsy tissue evaluation (1 day)

• Prevalence of colon polyps

  determined at the date of colonoscopy (1 day)

Study Arms (3)

Control

The target population for this study is male and female patients (age 18 to 80) and will consist of retired and active military personnel and their dependents. There will be no race, ethnic, or gender limitations to enrollment. The control group will be made of individuals who do not meet the qualifications for a liver biopsy.

Other: non-applicable

NAFLD

The target population for this study is male and female patients (age 18 to 80) and will consist of retired and active military personnel and their dependents. There will be no race, ethnic, or gender limitations to enrollment. The NAFLD group will be made of individuals who qualify for a liver biopsy and have histologically proven NAFLD.

Other: non-applicable

NASH

The target population for this study is male and female patients (age 18 to 80) and will consist of retired and active military personnel and their dependents. There will be no race, ethnic, or gender limitations to enrollment. The NASH group will be made of individuals who qualify for a liver biopsy and have histologically proven NASH.

Other: non-applicable

Interventions

non-applicable OTHER

non-applicable

Control; NAFLD; NASH

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

The patient population will include all adults presenting to the BAMC Gastroenterology clinic. The target population for this study is male and female patients (age 18 to 80) and will consist of retired and active military personnel and their dependents. BAMC is the only study site. There will be no race, ethnic, or gender limitations to enrollment.

You may qualify if:

• Phase I:
• Male and female patients (≥18 years of age to 80)
• Eligible for care at Brooke Army Medical Center
• Phase II:
• Met the criteria for qualification for a percutaneous liver biopsy and completed Phase I
• Eligible for care at Brooke Army Medical Center

You may not qualify if:

• Phase I:
• Patients with excessive alcohol use will be excluded as defined as \>21 units of alcohol/week for men and 14 units of alcohol/week for women over a 2 year time frame. One drink "unit" or one standard drink is equivalent to a 12-ounce beer, a 4-ounce glass of wine, or a 1-ounce shot of hard liquor.
• Patients with prior history of liver disease to include chronic hepatitis B or C, hemochromatosis, Wilson's disease, autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, HIV, or prior documentation of NAFLD.
• Patients on medications known to cause fatty liver disease: tamoxifen, corticosteroids, amiodarone, methotrexate, valproic acid
• Patients carrying an implantable active medical device such as a pacemaker or a defibrillator
• Pregnant women
• Phase II:
• CCTA/CAC only: GFR \<60 mls/min/1.73m2 or IV contrast dye allergy
• CCTA/CAC only: contraindications to atrioventricular (AV) nodal blocking agents (high degree AV block without permanent pacemaker, asthma, allergy to nodal blocking agents).
• Known CAD defined as previous PCI or CABG (Note: Subjects with CCTA within the past 12 months will not be excluded from study and repeat scan will not be needed but the results of that previous scan will be included in the prevalence and severity analysis.)

Sponsors & Collaborators

• The Geneva Foundation: lead

Study Sites (1)

San Antonio Military Medical Center

Fort Sam Houston, Texas, 78234, United States

Location

Related Publications (1)

• Dennis A, Kelly MD, Fernandes C, Mouchti S, Fallowfield JA, Hirschfield G, Pavlides M, Harrison S, Chakravarthy MV, Banerjee R, Sanyal A. Correlations Between MRI Biomarkers PDFF and cT1 With Histopathological Features of Non-Alcoholic Steatohepatitis. Front Endocrinol (Lausanne). 2021 Jan 27;11:575843. doi: 10.3389/fendo.2020.575843. eCollection 2020.

  PMID: 33584535 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

An additional 5 ml of whole blood and 5 ml of serum will be collected and stored by a research coordinator, nurse, research assistant, or investigator for analysis of specific biomarkers to include Hyaluronic acid, CK-18 (M30), FGF-21, Mac-2BP, FAS, AFP, YKL-40, Alpha-2-macroglobulin and a panel of 46 fatty acids during the liver biopsy appointment.

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Coronary Artery Disease

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases; Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Study Officials

• Angelo H Paredes, MD

  Brooke Army Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 1, 2017
• First Posted: May 8, 2017
• Study Start: August 25, 2015
• Primary Completion: June 27, 2019
• Study Completion: June 27, 2019
• Last Updated: February 24, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)