Genetic predisposition, lifestyle risk, and obesity associate with the progression of nonalcoholic fatty liver disease

Abstract

BackgroundNonalcoholic fatty liver disease (NAFLD) is prevalent worldwide. We aim to identify the factors promoting NAFLD progression. MethodsUK Biobank study participants were diagnosed for whether NAFLD presented at baseline. Cox regression model was used to examine the association of risk factors with incident diseases (significant liver diseases [SLDs], type 2 diabetes [T2D], cardiovascular diseases [CVDs], chronic kidney diseases [CKDs], and cancers) among NAFLD cases. ResultsOf 78 283 individuals, 35 159 (44.9%) were females, and the mean (SD) age was 57.56 (7.90) years. Compared with participants had both low genetic and lifestyle risk, individuals with both high genetic and lifestyle risk had a hazard ratio of 1.64 (95% CI 1.32–2.03) for SLDs, 1.16 (1.08–1.24) for T2D, 1.25 (1.13–1.37) for CVDs, 1.33 (1.18–1.49) for CKDs, and 1.13 (1.05-1.22) for cancers. Compared with participants who were non-obese and had low genetic risk, those with obesity and high genetic risk had an 75% (95% CI 38–123%), 147% (128–167%), 46% (33–61%), and 76% (56–99%) increased risk for developing SLDs, T2D, CVDs, and CKDs, respectively. The population-attributable fractions suggested that lifestyle risk and obesity contributed more to the progression of NAFLD than genetic risk. ConclusionAdhering to a healthy lifestyle and avoiding obesity are important to prevent NAFLD progression.