Fatty liver disease (FLD), hepatic steatosis and fibrosis, often leads to cirrhosis and cancer. Among American Indians (AI), chronic liver disease is the fifth leading cause of death (CDC). However, few data exist on age-adjusted prevalence rates of chronic liver disease, and none on hepatic steatosis and fibrosis in AI. Risk factors include obesity, insulin resistance, alcohol consumption and viral hepatitis, but there are also few data available on the individual and combined influence of each of these factors on the development of fatty liver and its progression to fibrosis. The Strong Heart Study (SHS) is the largest multicenter, prospective, epidemiologic study in American Indians, and has shown that AI have higher rates of obesity, insulin resistance, type 2 diabetes mellitus (T2D), and CVD than other groups in the United States. Although the presence of viral hepatitis is relatively low (<1%) prior exams show that >65% of SHS participants have elevated aminotransferase levels indicating liver injury; there is a wide range of alcohol consumption (with a majority reporting none [59%] or binge drinking [33%]). Given the high prevalence of known metabolic risk factors, the wide range of alcohol consumption and the availability of longitudinal data, the SHS of AI represents an excellent cohort with which to ask questions on the prevalence, cross-sectional associations and prospective determinants for hepatic steatosis and fibrosis, and could yield unique and valuable information on the links between insulin resistance, alcohol consumption and FLD. This study will use advanced magnetic resonance imaging (MRI) of the liver to non-invasively assess hepatic steatosis by MRI-derived proton density fat fraction (MRI-PDFF) and hepatic fibrosis by MR elastography-derived stiffness (MRE-stiffness) in a population-based sample of AI participants of the SHS. We propose to identify cross-sectional associations and longitudinal determinants of hepatic steatosis and fibrosis in AI from the SHS. We anticipate that we will gain an understanding of the longitudinal determinants explaining the increased rate of chronic liver disease in AI and identify important targets of intervention and prevention of FLD in populations with high rates of metabolic disease.

Public Health Relevance

Chronic liver disease is the fifth leading cause of mortality in American Indian (AI) and Alaska Native populations. There are currently no data available on the development of fatty liver disease (steatosis) and fibrosis, early manifestations of chronic liver disease, in AI. Metabolic disease and alcohol are each associated with fatty liver disease, but their relative impact on its presence and severity are unknown. This study will use state-of-the-art MRI of the liver to assess liver fat and fibrosis among a broad cohort of American Indians with high rates of insulin resistance and variable alcohol use, so as to characterize metabolic and environmental determinants of fatty liver disease.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Special Emphasis Panel (ZDK1-GRB-8 (M5)S)
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Unalp-Arida, Aynur
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Texas Biomedical Research Institute
San Antonio
United States
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Yokoo, Takeshi; Serai, Suraj D; Pirasteh, Ali et al. (2018) Linearity, Bias, and Precision of Hepatic Proton Density Fat Fraction Measurements by Using MR Imaging: A Meta-Analysis. Radiology 286:486-498