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/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 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.