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

Details

• Personal Author:
  Branch AD ; Jirapatnakul A ; Lewis SA ; Li L
• Description:
  This project is the first systematic investigation of liver disease in the Mount Sinai World Trade Center (WTC) General Responder Cohort (GRC). Currently, General Responders enrolled in the Mount Sinai WTC health program (WTCHP) 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 airborne 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. Toxicant-associated fatty liver disease (TAFLD) is an important type of NAFLD that is often associated with work place exposures to chemicals. This project addresses the need for a greater understanding of susceptibility factors for NASH and other progressive liver diseases in WTC General Responders. 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 and/or liver failure. To achieve our long term goal of reducing liver-related morbidity and mortality among people exposed to the WTC attack, in this project, we developed and then applied two sets of innovative diagnostic tools, a computer algorithm to automatically detect hepatitis steatosis (excess liver fat) in chest CT images and a series of phenotyping algorithms to detect NASH/TAFLD, primary liver cancer, and hepatitis C virus infection based on electronic health record (EMR) data. We had five major findings: [1] The odds ratio for moderate-to-severe hepatic steatosis was 3.4-fold higher in members of the WTC GRC than in non-WTC participants in a propensity score analysis that used inverse probability weighting; [2] The novel automated method for measuring liver attenuation and thereby detecting hepatic steatosis was highly accurate and had almost perfect agreement with manual methods, validating its use in clinical care and research; [3] The phenotyping algorithms accurately identified patients with fatty liver disease, liver cancer, and hepatitis C virus infection and was successfully used to increase linkage to care; [4] The number of WTC GRC members with primary liver cancer is rising steeply, as expected in a population with a high prevalence of NAFLD/TAFLD and other liver diseases, heightening concern about the lack of systematic liver disease screening; and [5] There is a dose-response relationship between the intensity of exposure to the WTC dust cloud and the prevalence of hepatitis steatosis. This project produced valuable new diagnostic tools and revealed that liver disease is highly prevalent among WTC responders, paving the way for improved liver disease management in the future. [Description provided by NIOSH]
• Subjects:
  Cohort Studies Communicable Diseases Emergency Responders Liver Neoplasms Occupational Health Safety September 11 Terrorist Attacks
• Keywords:
  Cancer Rates Cohort Studies Emergency Responders Hepatitis Hepatotoxicity Liver Disease Rescue Workers Surveillance World Trade Center WTC
• Series:
  Grant Final Reports
• Publisher:
  National Institute for Occupational Safety and Health
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Final Cooperative Agreement Report
• Place as Subject:
  New York ; OSHA Region 2
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  OEP - Office of Extramural Programs
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  1-19
• NIOSHTIC Number:
  nn:20066950
• Citation:
  Atlanta, GA: U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, U01-OH-011489, 2022 Nov; :1-19
• Contact Point Address:
  Andrea D. Branch, PhD MS, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029-6574
• Email:
  andrea.branch@mssm.edu
• Federal Fiscal Year:
  2023
• Performing Organization:
  Icahn School of Medicine at Mount Sinai, New York
• Peer Reviewed:
  False
• Start Date:
  20170701
• Source Full Name:
  National Institute for Occupational Safety and Health
• End Date:
  20210630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:f54dee05810f49ce1c5c33f00b178b34138bae62c22a19132f9bcd2237605f6c9c54fa5347d75950c2d6694758ed3cf804b79728af3bf26f912f5608a5edea3b
• Download URL:
  https://stacks.cdc.gov/view/cdc/219176/cdc_219176_DS1.pdf
• File Type:
  [PDF - 741.16 KB ]