Environmental Liver Disease

Liver disease is a major global health problem. Fatty liver disease, or excess accumulation of lipids in
hepatocytes, affects more than 25% of the worldwide adult population, but children and adolescents may also
be affected. Chronic liver disease may progress to cirrhosis and liver cancer resulting in liver-related death or
transplantation. Liver disease also impacts the development of diabetes and cardiovascular disease. Liver
diseases may be caused or influenced by exposures to environmental chemicals, but this is an understudied
area. To address these problems, this project establishes a major integrative and collaborative research
program, the Environmental Liver Disease Revolutionizing Innovative, Visionary Environmental Health Research
Program (ELD-RIVER).
ELD-RIVER will have a transformative impact in the field. The project investigates two broad scientific
themes: (i) the impact of endocrine and metabolism disrupting chemicals (EDCs/MDCs) in fatty liver disease,
and (ii) other liver diseases (such as liver cancer) associated with chemical exposures. The ELD-RIVER takes a
broad integrative scientific approach by investigating relevant chemicals; nutrient:chemical interactions; both
animal models and human subjects; and both sexes through state-of-the-art methods including multi-‘omics.
EDC/MDC exposures may also impact liver disease through their effects on obesity and diabetes. Thus, obesity
and diabetes endpoints will also be evaluated.
While the specific projects are expected to evolve over time, the initial work focusses on exposures to
polychlorinated biphenyls and vinyl chloride. Both of these chemicals currently rank in the top five in the Agency
for Toxic Substances and Disease Registry (ATSDR) Substance Priority List. ELD-RIVER strictly adheres to the
principles of scientific rigor and reproducibility and data transparency and availability. ELD-RIVER leverages
existing collaborations between multiple organizations including academia, government agencies, industry, and
scientific/medical societies. The vision is for ELD-RIVER to become the global hub for environmental liver
disease research. To accomplish its translational mission, the program integrates the work of basic scientists,
epidemiologists, and physicians. The project will also develop diagnostic biomarkers, new treatments, practice
guidelines, and it has the potential to impact policy change. Along the way, unique institutional education/training
resources will be utilized so that ELD-RIVER will help produce the next generation of environmental health
scientists. The work proposed is relevant to Strategic Plan of the National Institute of Environmental Health
Sciences (Themes 1, 2, and 5 and Goals 1, 4, 7, and 8).

Grant Number: 5R35ES028373-08
NIH Institute/Center: NIH
Principal Investigator: Matthew Cave