PREVALENCE AND PREDICTORS OF NONALCOHOLIC FATTY LIVER DISEASE (NAFLD) IN VETERANS

此应用程序的目的是确定非酒精性脂肪性肝病(NAFLD)在 在退伍军人事务部(VA)医疗系统接受初级护理的患者。非酒精性脂肪肝的影响 估计占美国成年非退伍军人管理局人口的20%-30%，预计将成为导致 在未来10年内将肝脏疾病分期。非酒精性脂肪肝的组织学范围从简单的 脂肪变性转变为非酒精性脂肪性肝炎(NASH)。大约20%的NASH患者经历了纤维化 进展为肝硬变，增加了肝功能衰竭的风险和肝细胞癌的风险。NAFLD是 考虑了肥胖和胰岛素抵抗的肝脏并发症。NAFLD和NAFLD的正确诊断 随后的治疗(例如，营养师服务)与生化和组织学的改善有关 非酒精性脂肪肝的特点。也有正在进行的临床试验，有希望的药物(例如，乙酰胆酸)可以治疗 纳什。 鉴于退伍军人受NAFLD主要危险因素(如糖尿病、 肥胖)，我们的中心假设是，初级保健中的退伍军人特别容易患上 NAFLD带来的高负担。目前尚不清楚退伍军人管理局目前是否有能力应对这种代价高昂的疾病。 由于缺乏关于NAFLD的患病率、决定因素和临床认识的基本信息， 弗吉尼亚州 磁共振成像(MRI)的进展彻底改变了脑血管疾病的诊断和严重程度分期 非酒精性脂肪肝，因此在大多数情况下不需要肝脏活检。然而，MRI在NAFLD筛查中的应用 在初级保健环境中是不切实际和昂贵的。没有就临床预测规则达成一致，而且 未在VA设置中进行测试。 我们将通过对1000名退伍军人(500名)进行基于概率的横断面研究来解决我们的假设 男性和500名女性)登记参加退伍军人管理局的初级保健。 具体目标1：确定NAFLD(和进展期)的总体和种族和性别特定的患病率 肝纤维化)在具有代表性的大样本中使用高度敏感和特异的MRI标准 退伍军人在休斯顿的迈克尔·E·德巴基退伍军人医疗中心登记参加他们的初级医疗保健。这 目的将通过联合使用肝脏磁共振成像质子密度脂肪分数来实现 (MRI-PDFF)和弹性成像(MRE)。 具体目标2：评估NAFLD的存在和严重程度与潜在风险之间的关联 因素，包括人口统计(性别、种族/民族)、人体测量(BMI、腰围和身体 生物阻抗分析的脂肪)、临床(病史、家族史和药物)、血清学(CD18)、 遗传(PNPLA3)、生化(LFTs，肝纤维化和脂肪变性的血清生物标志物)、代谢 (代谢综合征的血清学标志物)和生活方式(吸烟、酒精、锻炼)因素。 具体目标#3：使用有关风险因素和生物标记物的信息来构建和验证算法 可以在初级保健水平上用来识别NAFLD和NASH的高危患者，以便进一步 转介。 不同群体的患病率信息对于有效的退伍军人管理局医疗规划和 资源配置。这项研究将有助于临床认识退伍军人事务部初级保健环境中的NAFLD VA特有的危险因素。最后，我们的研究将提供支持未来研究发展所需的数据 检测和转诊的临床路径。

The objective of this application is to determine the burden of non-alcoholic fatty liver disease (NAFLD) among patients receiving primary care at the Department of Veterans Affairs (VA) health care system. NAFLD affects an estimated 20%-30% of the adult non-VA US population and is projected to become the main cause of end- stage liver disease in the next 10 years. NAFLD encompasses a histologic spectrum ranging from simple steatosis to non-alcoholic steatohepatitis (NASH). Around 20% of patients with NASH undergo fibrotic progression to cirrhosis, which increases risk of liver failure the risk of hepatocellular carcinoma. NAFLD is considered the hepatic complication of obesity and insulin resistance. Proper diagnosis of NAFLD and subsequent treatment (e.g., dietitian services) is associated with improved biochemical and histological features of NAFLD. There are also ongoing clinical trials with promising medications (e.g., obeticholic acid) for NASH. Given the veteran population is disproportionately affected by the main risk factors for NAFLD (e.g., diabetes, obesity), our central hypothesis is that the veteran population in primary care is particularly susceptible to a high burden from NAFLD. It is unclear whether the VA is currently equipped to deal with this costly disorder given the lack of basic information on the prevalence, determinants, and clinical recognition of NAFLD in the VA. Advances in magnetic resonance imaging (MRI) has revolutionized the diagnosis and severity staging of NAFLD, thus obviating the need for liver biopsy in most cases. However, the use of MRI for NAFLD screening in a primary care setting is impractical and expensive. There are no agreed upon clinical prediction rules, and none that is tested in VA settings. We will address our hypothesis by conducting a probability-based cross-sectional study of 1000 veterans (500 males and 500 females) enrolled in the VA for their primary healthcare. Specific Aim #1: To determine the overall and race- and sex- specific prevalence of NAFLD (and Advanced Hepatic Fibrosis) using highly sensitive and specific MRI criteria in a large and representative sample of veterans enrolled at the Michael E. DeBakey VA Medical Center in Houston for their primary healthcare. This aim will be accomplished by combined use of liver magnetic resonance imaging proton density fat fraction (MRI-PDFF) and elastography (MRE). Specific Aim #2: To evaluate the association between presence and severity of NAFLD and potential risk factors, including demographic (gender, race/ethnicity), anthropometric (BMI, waist circumference, and body fat by bioimpedance analysis), clinical (medical history, family history, and medications), serologic (CD18), genetic (PNPLA3), biochemical (LFTs, serologic biomarkers of hepatic fibrosis and steatosis), metabolic (serologic markers of metabolic syndrome), and lifestyle (smoking, alcohol, exercise) factors. Specific Aim #3: Use the information on risk factors and biomarkers to construct and validate an algorithm that can be used at the primary care level to identify patients at high risk of NAFLD and NASH for further referral. The information on prevalence in different groups are essential for effective VA healthcare planning and resource allocation. The study will aid in the clinical recognition of NAFLD in the VA primary care setting using VA specific risk factors. Finally, our study will provide data needed to support future research to develop clinical pathways for detection and referral.