The Prevalence of Nonalcoholic Fatty Liver Disease (NAFLD) in Adults
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 826
- 试验地点
- 1
- 主要终点
- Prevalence of NAFLD
研究概览
简要总结
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.
详细描述
In this prospective study, adult patients ranging in age from 18-80, routinely seen in the Brooke Army Medical Center Gastroenterology clinics will be eligible for enrollment. Approximately 950 adult patients will be enrolled. In phase I the prevalence of NAFLD and NASH will be determined, non-invasive imaging techniques for the diagnosis of NAFLD and NASH will be explored, and the relationship between colon polyps and NAFLD will be evaluated. Phase II will be offered to participants that qualified for a liver biopsy. In phase II the prevalence and severity of CAD, endothelial dysfunction, and diastolic dysfunction within the population of subjects with NAFLD will be determined.
Phase I:
After obtaining informed consent and confirming that the subject has met inclusion and exclusion criteria for the study, the study will employ a questionnaire to be completed by the subject. This questionnaire will include data such as race and ethnic group, past medical history, current medications, etc. The subject will then have routine labs (liver function tests, fasting insulin, glucose, and a pregnancy test for all female subjects), FibroScan® and MRE/MRI done to assess for the presence or absence of hepatic steatosis, inflammation, fibrosis, iron quantification and diameter and luminal characteristics of the abdominal aorta. Subjects will be called by the PI or an AI to return to the clinic for additional study procedures to include a core liver biopsy if they are identified to have one or more of the following:
- greater or equal to 5% steatosis on MRI or
- liver stiffness greater than 7 kPa on Fibroscan®, or
- evidence of fibrosis on MRE or
- LIF score of 2.0 or greater
The PI/AI will let the subject know that he/she qualifies for further diagnostic testing as part of the trial and will discuss tests results with them in detail.
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male and female patients (≥18 years of age to 80)
- •Eligible for care at Brooke Army Medical Center
- •Met the criteria for qualification for a percutaneous liver biopsy and completed Phase I
- •Eligible for care at Brooke Army Medical Center
排除标准
- •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
- •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.)
结局指标
主要结局
Prevalence of NAFLD
时间窗: from the date of consent to the completion of phase I (up to 3 months)
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.
Prevalence of NASH
时间窗: from the date of consent to the completion of phase I (up to 3 months)
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.
次要结局
- 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))
- Stages of fibrosis and grades of steatosis(determined at the date of liver biopsy tissue evaluation (1 day))
- Prevalence and severity of CAD(determined at the date of CCTA (1 day))
- Prevalence and severity of endothelial dysfunction with peripheral tonometry(determined at the date of the EndoPat Test (1 day))
- Liver stiffness measure by MRE(Determined at the date of MRE (1 day))
- Prevalence of colon polyps(determined at the date of colonoscopy (1 day))
- Prevalence of diastolic dysfunction(determined at the date of the transthoracic echocardiogram (1 day))