Weight Change and the Development of Non-Alcoholic Fatty Liver Disease in Metabolically Healthy Overweight Individuals

Abstract Introduction To investigate the effect of weight change on hepatic steatosis (HS) incidence with or without liver fibrosis in metabolically healthy overweight or obese individuals. Methods A cohort of 14,779 metabolically healthy men and women who were overweight or obese (BMI ≥23 kg/m2) and free from HS and an intermediate or high probability of fibrosis at baseline were followed for a median of 5.2 years. Metabolic health was defined as freedom from the components of metabolic syndrome and a homeostasis model assessment of insulin resistance Results During 76,794.6 person-years of follow-up, 3,539 cases of HS incidence were identified. The multivariable adjusted hazard ratios (95% confidence intervals) for HS incidence by weight change group, 5.0%, relative to the no weight change group (-0.9% to 0.9%) were 0.52 (0.44–0.60), 0.83 (0.75–0.92), 1.21 (1.10–1.33), and 1.51 (1.36–1.69), respectively. Clinically relevant weight loss of >5% was also associated with a lowered risk of HS with intermediate or high probability of advanced fibrosis. In mediation analyses, associations remained significant, although adjustment for metabolic risk factors was attenuating. Discussion Clinically relevant weight loss was associated with a reduced risk of developing non-alcoholic fatty liver disease with or without intermediate or high probability of advanced fibrosis in metabolically healthy overweight or obese individuals.