Impact of Body Weight Gain on the Incidence of Nonalcoholic Fatty Liver Disease in Nonobese Japanese Individuals

INTRODUCTION: We aimed to investigate the effect of recent short-term weight gain on the incidence of nonalcoholic fatty liver disease (NAFLD) in nonobese (body mass index < 25 kg/m 2 ) participants. METHODS: This retrospective cohort study included nonobese individuals who participated in an annual health checkup between 2008 and 2018 in Tokyo, Japan. We estimated the multivariable adjusted hazard ratio for the development of NAFLD diagnosed via ultrasound after a 3-kg unit gain in weight measured at a 2-year landmark time point postbaseline. Multivariable adjustments included weight change from the age of 20 and other relevant confounding factors. Sensitivity analyses using additional landmark time points at 1, 3, 4, and 5 years postbaseline and time-dependent Cox proportional hazards regressions were performed. RESULTS: Among the 27,064 nonobese participants (142,699 person years of follow-up), 2,895 were diagnosed with NAFLD. Approximately 90% of the patients with NAFLD maintained their nonobese status before disease diagnosis. The adjusted hazard ratio for the development of NAFLD (for a 3-kg unit of weight gain) at the 2-year landmark time point postbaseline was 1.60 (95% confidence interval, 1.46–1.76) in nonobese men and 1.66 (95% confidence interval, 1.51–1.83) in nonobese women. This association was maintained in the sensitivity analyses. DISCUSSION: Recent short-term weight gain is an independent risk factor for NAFLD development in nonobese men and women. Clinicians should be mindful of the association between weight gain and NAFLD onset, even in the nonobese population.