Weight Change and the Development of Nonalcoholic Fatty Liver Disease in Metabolically Healthy Overweight Individuals

INTRODUCTION: The study sought 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 (body mass index >= 23 kg/m(2)) 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 homeostatic model assessment of insulin resistance <2.5. Weight changes were calculated as differences from baseline at the next subsequent visit. The outcome was HS incidence, with or without liver fibrosis, as assessed by liver ultrasound and 2 noninvasive fibrosis scores. RESULTS: During 76,794.6 person-years of follow-up, 3539 cases of HS incidence were identified. The multivariable adjusted hazard ratios (95% confidence intervals) for HS incidence by weight change group, <-5.0%, -5.0%-1.0%, 1.0%-5.0%, and >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 nonalcoholic fatty liver disease with or without intermediate or high probability of advanced fibrosis in metabolically healthy overweight or obese individuals.