Evidence of Toxicant-associated Fatty Liver Disease in WTC Responders

世贸中心应急人员中存在与毒物相关的脂肪肝的证据

• 批准号: 10315788
• 负责人: Andrea D. Branch
• 金额: $ 49.9万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10315788
• 关键词: Evidence; Toxicant; associated; Fatty; Liver

Evidence of Toxicant-associated Fatty Liver Disease (TAFLD) in WTC Responders: The liver is the vital organ that is most-commonly damaged by occupational exposure to toxic chemicals; 30% of occupational and environmental toxins cause liver injury. The World Trade Center (WTC) dust cloud contained many known hepatotoxins, increasing the risk of liver cancer and toxicant associated fatty liver disease (TAFLD), including the most serious form of TAFLD--toxicant-associated steatohepatitis (TASH). Unfortunately, toxic liver injury and liver cancer risk often persist indefinitely. (Workers exposed to vinyl chloride are continuing to die from liver cancer decades after their direct toxic exposure ended). During the long latency period, there are often few overt symptoms of liver disease. Because of this, a proactive approach is needed to identify high-risk patients and engage them in care. Early detection of liver cancer increases survival, and life-extending interventions are available for nearly all liver diseases. Members of the WTC general responder cohort (GRC) receive WTC- certified healthcare from our occupational health specialist, Dr. Michael Crane. However, most liver diseases are not WTC-certified conditions and thus responders are not systematically tested for them. We are developing innovative tools to identify responders (and other people) likely to have undiagnosed TAFLD/TASH. Liver steatosis is a defining feature of TAFLD/TASH, but it cannot be detected by blood tests and thus often goes undiagnosed unless patients are receiving specialty liver care. Fatty liver can, however, be detected in chest CT scans, and also based on data in electronic (EHRs), as we have shown. Due to their severe respiratory symptoms, thousands of WTC responders have had chest CT scans. To accelerate image analysis, we developed and validated a novel computer algorithm that allows data from thousands of scans to be extracted automatically. Using this algorithm, we recently discovered that liver steatosis is directly related to the intensity of exposure to WTC dust (Preliminary Results). Although liver steatosis is a feature of many liver diseases, fatty liver is not always a progressive condition. In patients with fatty liver disease, fibrosis (scar) is the most important mortality risk factor. Herein, we evaluate CT-defined liver steatosis as an imaging biomarker of liver disease risk, as indicated by fibrosis (Aim I), determine disease severity of WTC responders with fatty liver disease, as defined by our EHR-based algorithm (Aim II), compare mortality of WTC responders with liver fibrosis, defined as a fibrosis (FIB)-4 score ≥ 1.3, to that of other responders and to the general population (Aim III), and evaluate the impact of liver fibrosis on health related quality of life (HRQL) in responders enrolled in a WTC Liver Disease Registry (Aim IV). This project will use novel diagnostic tools (CT-based and EHR-based) to identify WTC responders with fatty liver disease and fibrosis, allowing them to receive appropriate care. The findings will provide unprecedented detail about occupational liver disease, helping to inform public policy. The WTC Liver Disease registry will collect valuable data about the impact of liver disease on quality of life.

WTC应答者中毒物相关性脂肪肝（TAFLD）的证据：肝脏是重要的 最常因职业接触有毒化学品而受损的器官; 30%的职业和 环境毒素导致肝损伤。世界贸易中心（WTC）尘埃云包含许多已知的 肝毒素，增加肝癌和毒物相关性脂肪肝病（TAFLD）的风险，包括 TAFLD最严重的形式--毒物相关性脂肪性肝炎（TASH）。不幸的是，中毒性肝损伤和 肝癌的风险往往会无限期地持续下去。（接触氯乙烯的工人继续死于肝脏疾病。 在他们直接接触有毒物质几十年后才患上癌症）。在漫长的潜伏期内， 肝病的症状因此，需要采取积极主动的方法来识别高风险患者， 让他们在照顾。早期发现肝癌可以提高生存率，延长生命的干预措施是 可用于几乎所有肝脏疾病。WTC一般应答队列（GRC）的成员接受WTC- 由我们的职业健康专家Michael起重机博士认证的医疗保健。然而，大多数肝脏疾病 没有WTC认证的条件，因此响应者没有对其进行系统测试。我们正在开发 创新的工具，以确定响应者（和其他人）可能有未确诊的TAFLD/TASH。肝 脂肪变性是TAFLD/TASH的一个定义特征，但它不能通过血液检查检测到，因此通常会 除非患者正在接受专业的肝脏护理，否则无法诊断。然而，脂肪肝可以在胸部检测到 CT扫描，也基于电子数据（EHR），正如我们所示。由于严重的呼吸道感染 症状，数以千计的世贸中心响应者进行了胸部CT扫描。为了加速图像分析，我们 开发并验证了一种新的计算机算法，可以从数千次扫描中提取数据 的自动使用这种算法，我们最近发现肝脏脂肪变性与强度直接相关， 暴露于WTC粉尘（初步结果）。虽然肝脏脂肪变性是许多肝脏疾病的特征， 脂肪肝并不总是一种进行性疾病。在脂肪肝患者中，纤维化（瘢痕）最多， 重要的死亡风险因素。在此，我们评估CT定义的肝脏脂肪变性作为肝脏的影像学生物标志物， 疾病风险，如纤维化（目的I）所示，确定WTC应答者脂肪肝的疾病严重程度 根据我们基于EHR的算法（Aim II）的定义，将WTC应答者的死亡率与肝脏 纤维化，定义为纤维化（FIB）-4评分≥ 1.3，与其他应答者和一般人群相比（目的 III），并评估肝纤维化对参加研究的应答者健康相关生活质量（HRQL）的影响。 WTC肝病登记（Aim IV）。该项目将使用新的诊断工具（基于CT和基于EHR）， 识别患有脂肪肝和纤维化的WTC反应者，使他们能够接受适当的护理。的 调查结果将提供有关职业性肝病的前所未有的细节，有助于为公共政策提供信息。的 WTC肝病登记处将收集有关肝病对生活质量影响的宝贵数据。