Individualized Effects of Weight Gain in Adulthood on the Development of MASLD in Japanese Non-Obese Individuals.

BACKGROUND

This study aimed to estimate the individualized effect of weight change since age 20 on the development of metabolic dysfunction-associated steatotic liver disease (MASLD) in Japanese non-obese individuals. We also assessed the clinical characteristics of high-risk individuals with weight gain.

METHOD: This retrospective cohort study included non-obese individuals who underwent health examinations at St. Luke's International Hospital between 2008 and 2018. We developed a counterfactual prediction model using logistic regression to predict the risk of MASLD onset within 3 years and predicted counterfactual risks for 5 weight change scenarios: (i) weight loss < -3 kg, (ii) weight maintenance: ±3 kg, (iii) 3.1-6 kg gain, (iv) 6.1-9.9 kg gain, and (v) major weight gain ≥ 10 kg. Individualized effects of weight change were estimated using a risk difference scale, with variability assessed through their distributions and forest plots.

RESULTS

A total of 20 886 individuals (64.4% women) were included, and 2016 (9.6%) developed MASLD within 3 years. The counterfactual prediction model showed the average risk difference for major weight gain ≥ 10 kg was 6.6% (median: 5.1%), with individual risk differences varied from 2% to 19% across individuals. Forest plot showed an increased average risk of 5% for men, abdominal obesity, dyslipidemia, hyperuricemia, and high ALT levels.

CONCLUSION

Weight change since age 20 is a significant risk factor for MASLD development in non-obese populations, but its impact varies widely among individuals. Men and individuals with abdominal obesity, dyslipidemia, hyperuricemia, and high ALT levels are particularly susceptible to the effects of weight gain.