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.

Narrative This project will use our newly-developed and novel diagnostic tools [computer tomography (CT)-based and electronic health record (EHR)-based] to identify members of the World Trade Center (WTC) General Responder Cohort (GRC) who have evidence of toxicant-associated fatty liver disease (TAFLD) and liver cancer. The findings will provide unprecedented detail about these occupational liver diseases, helping to inform public policy. A WTC Liver Disease registry will be established to collect data about the impact of liver disease on quality of life and other valuable information.