Evidence of Toxicant-associated Fatty Liver Disease in WTC Responders

WTC中毒物相关性脂肪性肝病(TAFLD)的证据应答者：肝脏是至关重要的 最常因职业接触有毒化学品而受损的器官；30%的职业和 环境毒素会导致肝脏损伤。世界贸易中心(WTC)的尘埃云包含许多已知的 肝毒素，增加患肝癌和毒物相关性脂肪肝的风险，包括 最严重的TAFLD形式--毒物相关性脂肪性肝炎(TASH)。不幸的是，中毒性肝损伤和 患肝癌的风险通常会无限期地存在。)接触氯乙烯的工人仍在继续死于肝脏 在他们的直接有毒接触结束后几十年，癌症)。在长潜伏期内，通常很少有显性的 肝脏疾病的症状。因此，需要一种积极主动的方法来识别高危患者和 让他们参与护理。及早发现肝癌可以提高存活率，而延长生命的干预措施 适用于几乎所有肝病。WTC一般响应者队列(GRC)的成员将获得WTC- 由我们的职业健康专家Michael Crane博士认证的医疗保健。然而，大多数肝病都是 没有WTC认证的条件，因此响应者没有进行系统的测试。我们正在开发 用于识别可能患有未确诊TAFLD/TASH的应答者(和其他人)的创新工具。肝 脂肪变性是TAFLD/TASH的一个定义特征，但它不能通过血液测试检测出来，因此经常 除非患者正在接受特殊的肝脏护理，否则无法诊断。然而，脂肪肝可以在胸部被检测到。 CT扫描，也基于电子病历(EHR)的数据，如我们所示。由于他们严重的呼吸道疾病 症状出现后，数以千计的WTC应答者接受了胸部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 自动的。使用这个算法，我们最近发现，肝脏脂肪变性与强度直接相关。 暴露于WTC粉尘的风险(初步结果)。尽管肝脏脂肪变性是许多肝病的一个特征， 脂肪肝并不总是进行性的。在脂肪肝患者中，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影像生物标记物。 疾病风险，如纤维化(目标I)所示，决定了患有脂肪肝的WTC应答者的疾病严重程度 疾病，由我们的基于EHR的算法(AIM II)定义，将WTC应答者的死亡率与肝脏进行比较 纤维化，定义为纤维化(FIB)-4分≥1.3，对其他应答者和普通人群(AIM Iii)，并评估肝纤维化对参加 WTC肝病登记中心(AIM IV)。该项目将使用新的诊断工具(基于CT和基于EHR)来 识别患有脂肪肝和纤维化的WTC应答者，使他们能够得到适当的护理。这个 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。这个 WTC肝病登记中心将收集有关肝病对生活质量影响的有价值的数据。

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.