Letter to the Editor: Healthy sleep patterns and metabolic dysfunction-associated steatotic liver disease - insights and considerations

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common chronic liver disease associated with metabolic disorders. We read with interest the observational study by Yu et al entitled “Mediating roles of insulin resistance and inflammatory markers between healthy sleep scores and metabolic dysfunction-associated steatotic liver disease”. Suboptimal sleep quality is increasingly recognized as a modifiable risk factor for this condition. Poor sleep patterns, assessed using healthy sleep scores including sleep duration, chronotype, insomnia, sleep apnea, and daytime sleepiness, are linked to increased risk of MASLD. Insulin resistance, remnant cholesterol, non-high-density lipoprotein cholesterol, and systemic inflammation contribute to this association, suggesting that improving sleep health may help prevent or mitigate metabolic liver disease. Further research integrating objective sleep monitoring, refined sleep assessment frameworks, circadian rhythm evaluation, lifestyle factors, metabolic biomarkers, and long-term liver outcomes are warranted to clarify the mechanisms linking sleep health and MASLD and facilitate clinical translation.

Key Words: Metabolic dysfunction-associated steatotic liver disease; Healthy sleep score; Sleep quality; Insulin resistance; Objective sleep assessment

Core Tip: Healthy sleep is increasingly recognized as a modifiable determinant of metabolic health. Integrating multidimensional sleep assessment with circadian, lifestyle, and metabolic factors may clarify mechanisms linking sleep and metabolic dysfunction-associated steatotic liver disease, supporting improved risk stratification and clinical translation.

TO THE EDITOR

I read with great interest the work of Yu et al[1] “Mediating roles of insulin resistance and inflammatory markers between healthy sleep scores and metabolic dysfunction-associated steatotic liver disease”, recently published in the World Journal of Gastroenterology. In the cited study, the authors systematically evaluated the association between healthy sleep scores and metabolic dysfunction-associated steatotic liver disease (MASLD) in a community-based Chinese population, providing important evidence for research and prevention. This commentary extends on their findings by emphasizing integrated sleep assessment, 24-hour lifestyle factors, circadian regulation, metabolic biomarkers, and long-term liver outcomes to improve MASLD risk stratification and clinical translation.

CURRENT SITUATION AND CHALLENGES OF MASLD MANAGEMENT

Healthy sleep is increasingly recognized as a modifiable factor associated with MASLD, a prevalent chronic liver condition worldwide in which metabolic dysfunction plays a central role in pathogenesis[2,3]. Lifestyle intervention remains an important strategy for MASLD prevention and management, and sleep health has recently attracted attention as a modifiable factor associated with metabolic and liver-related outcomes[4,5]. In the study by Yu et al[1] sleep behaviors, including sleep duration, chronotype, insomnia, sleep apnea, and daytime sleepiness, were integrated into the healthy sleep score, providing a multidimensional assessment of sleep health.

Poor sleep may drive the pathogenesis of MASLD through a multifaceted mechanism encompassing insulin resistance, dyslipidemia, systemic inflammation, and hepatic injury[5]. It is also proposed that obstructive sleep apnea may promote adverse liver-related outcomes through intermittent hypoxia, sympathetic activation, oxidative stress, and metabolic dysregulation[5,6]. However, the detailed mechanisms linking sleep health to MASLD remain incompletely understood[5]. Therefore, in addition to methodological issues such as subjective sleep assessment and cross-sectional design, several clinically relevant questions require further discussion. The potential pathways and future considerations linking sleep health to MASLD are summarized in Figure 1. A paradigm shift in research and clinical management is required regarding these future outlooks.

Figure 1 Potential pathways and future considerations linking sleep health to metabolic dysfunction-associated steatotic liver disease. Solid boxes and arrows indicate sleep-related factors, mediating indicators, liver assessment parameters, and associations reported in the original study. Dashed boxes and arrows indicate additional considerations, potential pathways, additional liver outcomes, and future research directions proposed in this commentary. HOMA-IR: Homeostasis model assessment of insulin resistance; RC: Remnant cholesterol; non-HDL-C: Non-high-density lipoprotein cholesterol; hs-CRP: High-sensitivity C-reactive protein; MASLD: Metabolic dysfunction-associated steatotic liver disease; VCTE: Vibration-controlled transient elastography; CAP: Controlled attenuation parameter; LSM: Liver stiffness measurement.

First, sleep health should be considered within a broader 24-hour lifestyle framework. Although sleep duration, chronotype, insomnia, sleep apnea, and daytime sleepiness were included in the healthy sleep score, bedtime regularity, sleep fragmentation, eating rhythm, physical activity, and sedentary behavior were not fully evaluated[7,8]. Considering the close relationship between circadian rhythm, dietary behavior, physical activity, and metabolic regulation, the combined effects of sleep and other lifestyle factors should be further explored[7,8]. Moreover, modern lifestyle patterns such as social jetlag and shift work may further disrupt circadian alignment by creating a mismatch between social schedules and endogenous sleep-wake rhythms. These circadian disruptions may influence metabolic homeostasis through altered eating patterns and metabolic regulation, thereby increasing susceptibility to metabolic dysfunction and MASLD development[7,9]. Furthermore, sex and hormonal status may represent important factors contributing to heterogeneity in MASLD susceptibility. Differences in sex hormones and metabolic regulation may contribute to varying susceptibility to MASLD and sleep-related metabolic disturbances[10,11]. Therefore, future studies should integrate broader lifestyle, circadian, and biological factors to better characterize the complex relationship between sleep health and MASLD risk.

Second, the healthy sleep score assigns equal weight to each component, although different sleep traits may not have equivalent biological effects. For example, obstructive sleep apnea, circadian disruption, and sleep fragmentation may have stronger effects on hepatic steatosis, insulin resistance, inflammation, and metabolic dysfunction than other sleep components[6,9,12]. Sleep duration may have a nonlinear association with metabolic health, as shorter and longer sleep durations have been associated with adverse metabolic outcomes[11,13]. Moreover, sleep duration alone may not adequately represent sleep health, because sleep continuity and sleep efficiency provide additional information on sleep-related metabolic risk. Recent objective sleep assessment has shown that individuals with MASLD exhibit increased nocturnal wakefulness, fragmented sleep patterns, and reduced sleep efficiency, highlighting the importance of evaluating sleep architecture beyond self-reported sleep duration[12]. Therefore, the association between sleep health and MASLD should not be interpreted as a simple one-to-one causal relationship. Instead, sleep duration, sleep quality, sleep disorders, circadian disruption, and metabolic factors may interact through multiple biological pathways, including altered metabolism, insulin resistance, and inflammation, contributing to MASLD development[5]. Future studies may therefore consider developing more refined sleep assessment frameworks, including weighted sleep scores or integrated sleep-metabolic risk models that account for diverse sleep phenotypes and their interactions with metabolic pathways, to better characterize MASLD risk.

Third, the clinical application of the mediating indicators warrants attention. Homeostasis model assessment of insulin resistance, high-sensitivity C-reactive protein, remnant cholesterol, and non-high-density lipoprotein cholesterol may help explain the association between sleep health and MASLD, but whether these markers can guide screening, risk stratification, or sleep-focused intervention remains uncertain[14]. In addition, the gut microbiome may represent another potential pathway linking circadian disruption and MASLD, as alterations in circadian rhythm can affect gut microbiota composition and contribute to hepatic steatosis and metabolic dysfunction[7,15]. Given the high prevalence of diabetes in the original study population, the potential influence of glucose-lowering medications should also be considered. Future studies should clarify medication use and incorporate glucose-lowering therapy into analyses evaluating the association between sleep health and MASLD. Moreover, long-term liver-related outcomes, such as fibrosis progression, steatohepatitis, cirrhosis, and hepatocellular carcinoma, should be further assessed[4]. Objective sleep monitoring and longitudinal follow-up would provide more robust evidence for causality and clinical translation[12,13].

CONCLUSION

In summary, the study by Yu et al[1] provides valuable evidence linking multidimensional sleep health to MASLD risk. Building on these findings, future research should integrate circadian regulation, lifestyle behaviors, metabolic biomarkers, and long-term liver outcomes to refine risk stratification and guide clinical translation. Strengthening sleep assessment frameworks may ultimately support more effective prevention and management strategies for MASLD.