Abstract

Background: Nonalcoholic Fatty Liver Disease (NAFLD) has increased in parallel with obesity, is a risk factor for cirrhosis and liver cancer, and has few effective treatments. Identifying modifiable risk factors for NAFLD development is essential to effectively design prevention programs. We tested whether trajectories of body mass index (BMI) change throughout early adulthood were associated with risk of prevalent NAFLD in midlife independent of current BMI. Methods: Participants from the CARDIA study, a prospective multicenter population-based biracial cohort of adults (baseline age 18-30 years), underwent BMI measurement at exam years 0, 2, 5, 7, 10, 15, 20, and 25. At Year 25 (Y25, 2010-2011), liver fat was assessed by computed tomography. NAFLD was identified after exclusion of other causes of liver fat (alcohol/hepatitis). Latent mixture modeling was used to identify 25-year trajectories in BMI percent (%) change relative to baseline BMI over time. Multivariable logistic regression models were used to assess associations between BMI trajectory group and prevalent NAFLD with adjustment for baseline or current Y25 BMI. Results: Among 4,423 participants, we identified 4 distinct trajectories of BMI %change: stable BMI (26.2% of the cohort, 25-year mean BMI Δ=0.7 kg/m 2 ), mild increase (46.0%, BMI Δ=5.2 kg/m 2 ), moderate increase (20.9%, BMI Δ=10.0 kg/m 2 ), and extreme increase (6.9%, BMI Δ=15.1 kg/m 2 ) (Figure). NAFLD prevalence at Y25 was higher with increasing BMI trajectory: 4.1%, 9.3%, 13.0%, and 17.6% (p-trend <0.0001). At baseline, 34.6% of participants had overweight or obesity. After adjustment for confounders, trajectories of greater BMI increase were associated with greater NAFLD prevalence independent of baseline or current Y25 BMI (Figure). Conclusion: Weight gain throughout adulthood is associated with greater prevalence of NAFLD in midlife independent of baseline or current BMI. These findings highlight weight maintenance throughout adulthood as a potential target for primary prevention of NAFLD.

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