1908-P: Factors Related to Hepatic Fat and Fibrosis in American Indians

Abstract

American Indians (AI) experience high rates of both liver disease and type 2 diabetes (T2D), yet few studies have investigated the contributions of T2D and other known risk factors to liver disease in AI. We used magnetic resonance imaging (MRI)-estimated proton density fat fraction (PDFF) and MR elastography (MRE)-estimated stiffness to assess hepatic fat and fibrosis, respectively, and assessed whether obesity, T2D, and heavy episodic alcohol (ETOH) consumption are associated with these liver measures in AI. The Strong Heart Family Study (SHFS) is a population-based family study of AI recruited from 12 communities located within Arizona (AZ), the Dakotas, and Oklahoma (OK). Metabolic measures were assessed during a clinic visit in 2006-2009. A re-exam including MRI and MRE has been conducted on 109 participants to date from AZ and OK (mean age 50.6 ± 11.3 years, 72% women, 71% obese (BMI ≥ 30 kg/m2), 57% had T2D, and 28% reported ETOH consumption). Median liver PDFF was 8.9% (1rst and 3rd quartiles: 4.3%, 14.6%), with 71% of participants having elevated liver fat (PDFF ≥ 5%). Median liver stiffness was 2.6 kPa, with 23% showing mild liver fibrosis (stiffness 2.8 - 3.63 kPa) and 8.3% advanced liver fibrosis (stiffness > 3.63 kPa). In cross-sectional analyses, liver PDFF was significantly higher in obese vs. non-obese participants (Wilcoxon rank sum test, p<0.0001). In longitudinal analyses using a generalized linear model, after adjusting for age, sex, and study site, obesity measures (waist p=0.005; BMI p=0.01), HbA1c (p=0.001), liver enzyme levels (ALT p=0.03) and serum uric acid (p=0.0002) were associated with elevated PDFF. Obesity (waist p=0.001; BMI p=0.02) and cigarette smoking (p=0.002) were associated with elevated liver stiffness. In our at-risk subsample of AI participants of the SHFS, participants commonly had elevated liver fat and liver fibrosis, with obesity being the major, common, associated risk factor. Disclosure S.A. Cole: None. W.C. Henderson: None. T. Ali: None. C. West: None. M.S. Middleton: Consultant; Self; Kowa Pharmaceutical Europe Co. Ltd., Median, Novo Nordisk Inc. Stock/Shareholder; Self; General Electric, Pfizer Inc. A. Silva: None. D.N. Batakis: None. A.L. Louie: None. B.V. Howard: None. J.D. Dvorak: None. R. Devereux: Consultant; Self; Acer. J.G. Umans: None. C. Sirlin: Advisory Panel; Self; AMRA Medical, Bristol-Myers Squibb Company, VirtualScopics. Consultant; Self; Fulcrum Therapeutics. Other Relationship; Self; Celgene Corporation, Enanta Pharmaceuticals, Inc., Genzyme, Gilead Sciences, Inc., Gilead Sciences, Inc., ICON plc., Intercept Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., NuSirt Biopharma, Inc., Shire, Synageva, Takeda Pharmaceutical Company Limited, VirtualScopics. Y. Zhang: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (R01DK110096)