Hepatotoxic Exposures, Progressive Fatty Liver Disease (NASH), and Liver Cancer Risk in the World Trade Center Health Program General Responder Cohort

WTC中的肝病响应者：该项目提供了第一次系统的肝病调查。 世界贸易中心(WTC)一般响应者队列(GRC)。目前，世贸中心的应答者没有接受筛查 对于肝病，尽管它们严重暴露在粉尘、空气中的颗粒物和化学物质中 已知会在其他人群中引起肝脏毒性。在动物身上的研究证实了空气对肝脏的毒性作用- 可吸入颗粒物(PM2.5)和化学品。接触有毒物质与非酗酒者有关 脂肪性肝炎(NASH)，非酒精性脂肪性肝病(NAFLD)的一种进行性形式，可导致肝脏 失败和肝癌。这个项目解决了对NASH和其他专业人员更好地了解的需要 WTC应答者中的进行性肝病。我们的初步结果表明，WTC暴露是一个风险因素- 对于肝脏脂肪变性，NASH的定义特征之一(另一个最有临床意义的特征是 纤维化)。因为肝病通常是一种沉默的杀手，在不可逆转的损害发生之前一直没有得到诊断 发生肝病时，必须主动筛查肝病。在早期和可治愈的阶段，许多肝脏 疾病是无症状的。晚期肝病可以灾难性地表现为转移性肝癌。 我们希望发现WTC的攻击使应答者暴露在肝毒素中，并导致脂肪变性和纤维化。 发现以前未被发现的肝病将使WTC的响应人员得到咨询和治疗。 目标一：目标是通过比较GRC来检验WTC暴露是肝病风险因素的假设 将成员(n=400)与对照组(n=400)的无应答者(n=400)进行多元线性回归分析- 肝脂肪溶解(亚胺1)和肝纤维化(亚胺2)。肝脏脂肪(脂肪变性)将使用FibroScan- CAP和CT衰减值；将分析两种方法之间的相关性(SubAim 3)。 WTC提供者将被告知高危患者(那些同时患有脂肪升高和纤维化的患者)，以加强护理。 目标二：目标是开发使能技术，以计算估计肝脏脂肪含量从低 使用非对比胸部CT图像(SubAim 1)，将该技术应用于5000 GRC的现有图像 成员(SubAim 2)，并使用两两比较的一般线性模型来检验假设 WTC暴露强度与肝脏脂肪之间存在线性剂量-反应关系(亚胺3)。 目标三：目标是确定晚期肝纤维化/肝硬变的患病率和危险因素。 GRC(SubAim 1)，开发先进的医疗信息学工具，通过计算识别患者 NASH、丙型肝炎和/或酒精性肝病(SubAim 2)，将这些工具与手动图表审查相结合，以降低 在大约2000名GRC成员中检测和分析包括肝癌在内的肝脏疾病， 医疗、药品和索赔数据；并向提供者提供反馈，加强护理(SubAim3)。 这些研究将产生前所未有的关于WTC暴露和肝病的数据，并产生创新的数字。 塔尔科技。他们可能会发现(以前被忽视的)肝病，立即改善护理。

Liver Disease in WTC Responders: This project provides the first systematic investigation of liver disease in the World Trade Center (WTC) general responder cohort (GRC). Currently, WTC responders are not screened for liver diseases, although they were heavily exposed to dust, airborne particulate matter, and chemicals known to cause liver toxicity in other populations. Studies in animals confirm the hepatotoxic effects of air- borne particulate matter (PM2.5) and chemicals. Toxic exposures have been associated with non-alcoholic steatohepatitis (NASH), a progressive form of non-alcoholic fatty liver disease (NAFLD) that can lead to liver failure and liver cancer. This project addresses the need for a greater understanding of NASH and other pro- gressive liver diseases in WTC responders. Our Preliminary Results suggest that WTC exposure is a risk fac- tor for liver steatosis, one of the defining features of NASH (the other feature of greatest clinical significance is fibrosis). Because liver disease is often a silent killer that remains undiagnosed until irreversible damage has occurred, it is essential to screen for liver disease proactively. During the early and curable stages, many liver diseases are asymptomatic. Advanced liver disease can present catastrophically as metastatic liver cancer. We expect to find that the WTC attack exposed responders to hepatotoxins and caused steatosis and fibrosis. Uncovering previously unrecognized liver disease will allow WTC responders to be counseled and treated. Aim I: The goal is to test the hypothesis that WTC exposure is a risk factor for liver disease by comparing GRC members (n=400) to a control group of non-responders (n=400) using multivariable linear regression to ana- lyze liver fat (SubAim 1) and liver fibrosis (SubAim 2). Liver fat (steatosis) will be estimated using FibroScan- CAP and CT attenuation values; the correlation between the two methodologies will be analyzed (SubAim 3). WTC providers will be notified of high risk patients (those with both elevated fat and fibrosis), enhancing care. Aim II: The goals are to develop enabling technology to computationally estimate liver fat content from low- dose non-contrast chest CT images (SubAim 1), to apply this technology to existing images of 5000 GRC members (SubAim 2), and to use general linear models with pairwise comparisons to test the hypothesis that there is a linear dose-response relationship between the intensity of WTC exposure and liver fat (SubAim 3). Aim III: The goals are to determine the prevalence of and risk factors for advanced fibrosis/cirrhosis in the GRC (SubAim 1), to develop advanced medical informatics tools to computationally identify patients with NASH, HCV, and/or alcoholic liver disease (SubAim 2), to combine these tools with manual chart review to de- tect and analyze liver diseases, including liver cancer, among the estimated 2000 GRC members with in-depth medical, pharmaceutical, and claims data; and to provide feedback to providers, enhancing care (SubAim3). The studies will yield unprecedented data about WTC exposure and liver disease and produce innovative digi- tal technologies. They are likely to uncover (previously overlooked) liver disease, immediately improving care.