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: 10459182
• 负责人: Andrea D. Branch
• 金额: $ 49.98万
• 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/10459182
• 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反应者中与毒物相关脂肪肝病（TAFLD）的证据：肝脏是重要的 受职业暴露于有毒化学物质的职业损害的器官； 30％的职业和 环境毒素会导致肝损伤。世界贸易中心（WTC）尘埃云包含许多已知的 肝毒素增加了肝癌和毒物相关脂肪肝病（TAFLD）的风险，包括 TAFLD-毒剂相关的脂肪性肝炎（TASH）最严重的形式。不幸的是，有毒肝损伤和 肝癌风险通常无限期地持续。 （暴露于氯化乙烯基的工人继续死于肝脏 直接有毒暴露结束后的数十年癌症）。在漫长的延迟期间，通常很少有公开 肝病的症状。因此，需要一种积极的方法来识别高危患者和 让他们照顾。肝癌的早期发现增加了生存，延长生命的干预措施是 用于几乎所有肝病。 WTC一般响应者队列（GRC）的成员接受WTC- 我们的占领健康专家Michael Crane博士获得了认证的医疗保健。但是，大多数肝病是 不是WTC认证的条件，因此没有系统地测试响应者。我们正在发展 识别响应者（和其他人）的创新工具可能会无法诊断出TAFLD/TASH。肝 脂肪变性是TAFLD/TASH的一个定义特征，但无法通过血液检查检测到它，因此经常进行 除非患者接受特殊肝脏护理，否则未诊断。但是，可以在胸部检测到脂肪肝 如我们所示，CT扫描以及基于电子（EHR）的数据。由于其严重的呼吸系统 症状，成千上万的WTC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型的计算机算法，该算法允许提取数千张扫描的数据 自动地。使用该算法，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）。尽管肝脏脂肪变性是许多肝病的特征，但 脂肪肝并不总是渐进的状况。在患有脂肪肝病的患者中，纤维化（疤痕）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成像生物标志物 如纤维化所示（AIM I），疾病风险确定WTC肝脏肝脏的疾病严重程度 根据我们基于EHR的算法（AIM II）所定义的疾病，将WTC反应者与肝脏的死亡率进行比较 纤维化，定义为纤维化（FIB）-4得分≥1.3，对其他响应者和普通人群的得分（AIM iii），并评估肝纤维化对健康相关生活质量（HRQL）的影响 WTC肝病注册中心（AIM IV）。该项目将使用新颖的诊断工具（基于CT和基于EHR） 确定WTC响应者患有脂肪肝病和纤维化，使他们能够获得适当的护理。这 调查结果将提供有关职业肝病的前所未有的细节，有助于告知公共政策。这 WTC肝病注册中心将收集有关肝病对生活质量的影响的宝贵数据。