Metabolic dysfunction-associated steatotic liver disease (MASLD) is a new term replacing non-alcoholic fatty liver disease (NAFLD) (Rinella et al., 2023a). MASLD is now the leading chronic liver disease in the world, with a global prevalence of approximately 30% (Yip et al., 2023; Younossi et al., 2023). In China, MASLD is projected to afflict 314.58 million individuals by 2030, representing the greatest growth in disease prevalence globally (Estes et al., 2018). In addition to liver-related disorders, MASLD confers increased risks of extrahepatic cancers, type 2 diabetes, cardiovascular disease (CVD), and all-cause mortality (Chan et al., 2024; Targher et al., 2024; Younossi et al., 2024). While several drugs are in advanced stages of development, no specific treatments have been approved by regulatory agencies (Petroni et al., 2021). A healthy lifestyle remains crucial to the prevention and treatment of MASLD (Karlsen et al., 2022), but substantial uncertainty remains on the role of specific lifestyle factors.

Previous epidemiological studies have shown that regular physical activity, optimal sleep duration, and a healthy diet are associated with a lower risk of NAFLD, whereas smoking, alcohol intake, sedentary behavior are associated with a higher risk of NAFLD (Jang et al., 2019; Jung et al., 2019; Katsagoni et al., 2017; Kim et al., 2022; Kim et al., 2020; Kwak et al., 2018; Yang et al., 2023), though the results are not entirely consistent. These various lifestyle factors are usually correlated and may affect the disease risk in concert. However, few studies have analyzed the joint associations of different lifestyle factors with MASLD. To our knowledge, only four cross-sectional studies (Deng et al., 2021; Koch et al., 2015; Nivukoski et al., 2020; Yang et al., 2023; Zhu et al., 2022) and a case-control study (Jahromi et al., 2023) examined combined lifestyle in relation to NAFLD; two prospective cohort study has jointly examined various lifestyle factors in relation to risk of NAFLD (He et al., 2023; Ling et al., 2023). Of note, lifestyle factors in these previous studies mainly included traditional lifestyle behaviors such as smoking and diet, without adequately taking into account the emerging risk factors such as sleep and sedentary behaviors (Kim et al., 2020; Peng et al., 2017). Sleep and sedentary behaviors are important components of modern lifestyle, which may interact with traditional lifestyles to modify risk of MASLD. Moreover, physical activity is an important lifestyle behavior in addition to sedentary time and sleep as all three comprise the 24-h activity profile analytic framework. However, evidence is currently lacking regarding the association of a healthy lifestyle simultaneously including physical activity, sleep, and sedentary behaviors with the risk of MASLD.

Therefore, in this large population-based prospective cohort study, we aimed to develop a novel healthy lifestyle score and to examine the association of a combination of lifestyle factors with the risk of MASLD.