Altitude and Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) in China: A Population-Based Study

Yufei Wang, Qiong Meng, Jin Zhang, Bing Guo, Nanyan Li, Qian Deng, Julinling Hu, Quzong Deji, Han Guan, Wangjiu Danzhen, Hui Yu, Zhifeng Li, and Junmin Zhou. Altitude and metabolic dysfunction-associated fatty liver disease (MAFLD) in China: a population-based study. <i>High Alt Med Biol.</i> 26:148-155, 2025. <b><i>Objectives:</i></b> The epidemiological evidence for the relationship between altitude and metabolic dysfunction-associated fatty liver disease (MAFLD) is scarce. This study aims to examine the altitude-MAFLD relationship and explore the potential mediators explaining the relationship. <b><i>Methods:</i></b> Data were derived from the China Multi-Ethnic Cohort. The participants' altitude information was extracted from their residential addresses. MAFLD was diagnosed based on radiographically confirmed hepatic steatosis and any one of the following three items: overweight/obese status, diabetes mellitus, or metabolic dysregulation. We performed multivariable logistic regression and mediation analyses to assess the altitude-MAFLD associations and potential mediators, respectively. In the mediation analysis, mediation proportion is an estimate of the extent to which the total effect (altitude-MAFLD association) is accounted for by the pathway through the mediators. <b><i>Results:</i></b> In total, 87,679 participants (female: 60.7%, mean age: 51.36 years) were included. The odds ratio of MAFLD was 1.61 (95% confidence interval [CI]: 1.52-1.71) between high and low altitudes, 1.52 (95% CI: 1.43-1.62) between high and middle altitudes, and 1.06 (95% CI: 1.01-1.10) between middle and low altitudes. Of the total estimated effect between high and low altitude, physical activity and vegetable intake accounted for 15.7% (95% CI: 12.8-19.1) and 3.8% (95% CI: 1.2-6.6), respectively. Of the total estimated effect between high and middle altitude, physical activity and vegetable intake accounted for 31.4% (95% CI: 26.2-34.8) and 2.3% (95% CI: 0.6-3.8), respectively. Of the total estimated effect between middle and low altitude, vegetable intake accounted for 11.8% (95% CI: 3.2-61.5). <b><i>Conclusion:</i></b> Higher altitude was associated with increased odds of MAFLD, and physical activity and vegetable intake mediated such association. Multifaceted efforts should be taken in public health to promote healthy lifestyles among higher altitude residents.