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The association of physical activity (PA) and diet quality with non-alcoholic fatty liver disease (NAFLD) and NAFLD-related fibrosis have never been examined in a representative sample of U.S. adults using a more precise form of measuring NAFLD. The purpose of this study was to assess the associations of PA and diet quality (Healthy Eating Index [HEI]-2015) with NAFLD and a subset with advanced fibrosis (F3-4) as assessed by vibration-controlled transient elastography with controlled attenuation parameter in a representative sample of U.S. adults. This cross-sectional analysis uses data from 2017-2018 National Health and Nutrition Examination Survey. NAFLD was defined as controlled attenuation parameter ≥285 dB/m, and high likelihood of advanced fibrosis as liver stiffness measurements ≥8.6 kPa. Associations of HEI-2015 from 24-h dietary recalls and self-reported PA and sedentary behavior were estimated in multivariable-adjusted logistic regression models of NAFLD and advanced fibrosis. In 2892 adults, the prevalence of NAFLD and advanced fibrosis was 35.6% and 5.6%, respectively. We found that high adherence to U.S. dietary recommendations (highest vs. lowest HEI-2015 tertile) and more PA (middle tertile vs. lowest) were associated with reduced odds of NAFLD (Adjusted OR and 95% CI; 0.60 (0.44, 0.84) and 0.65 (0.42, 0.99), respectively). More PA was inversely associated with advanced fibrosis (Adjusted OR = 0.35, 95%CI 0.16, 0.75). Diet quality and PA are associated with reduced odds of NAFLD, and PA may be critical even for those with advanced liver disease. These behaviors should be the focus of targeted public health interventions. [ABSTRACT FROM AUTHOR]