METABOLIC dysfunction-associated steatotic liver disease (MASLD) represents a rising global health concern, affecting approximately 25% of the world’s population. MASLD, considered the hepatic manifestation of metabolic syndrome, spans a spectrum from benign hepatic fat accumulation to metabolic dysfunction-associated steatohepatitis (MASH), which can progress to fibrosis, cirrhosis, and hepatocellular carcinoma.
Emerging evidence highlights the critical role of circadian dysfunction in MASLD pathogenesis. The circadian rhythm, regulated by the central circadian clock in the hypothalamus, orchestrates physiological processes across peripheral tissues, ensuring metabolic synchrony. Disruption of this rhythm, caused by environmental factors like altered sleep patterns, nocturnal light exposure, and shift work, has been associated with obesity, insulin resistance, and hepatic fat accumulation. Experimental studies in murine models reveal that circadian clock gene deficiencies contribute to hyperphagia, metabolic syndrome, and MASLD progression.
In humans, studies employing self-reported sleep questionnaires have demonstrated associations between short sleep duration, fragmented sleep, and MASLD. Our study is the first to employ actigraphy – an objective tool for sleep assessment – to evaluate sleep patterns in patients with biopsy-proven MASLD, healthy controls (HC), and those with cirrhosis of other origins. Actigraphy revealed prolonged nocturnal wakefulness, increased sleep fragmentation, and reduced sleep efficiency in MASLD patients, despite similar sleep duration to HC. Subjectively, patients reported shorter sleep durations and delayed onset, consistent with previous findings.
These disruptions may play a pathophysiological role in MASLD development. Fragmented sleep has been linked to insulin resistance, a key factor in MASLD progression, and increased pro-inflammatory cytokine levels that promote hepatic fat accumulation. While melatonin—a circadian regulator with antioxidant properties—shows therapeutic promise in metabolic disorders, its role in MASLD remains unclear.
Importantly, a single session of sleep hygiene education (SHE) failed to improve sleep efficiency, suggesting the need for repetitive interventions or alternative therapies, such as melatonin supplementation. Although our study underscores the association between sleep fragmentation and MASLD, further research using polysomnography, larger cohorts, and targeted interventions is warranted to clarify causality and therapeutic potential.
Improving sleep efficiency may offer a novel strategy for managing MASLD, addressing both metabolic and hepatic dysfunction, and mitigating disease progression.
Katie Wright, EMJ
Reference
Schaeffer S et al. Significant nocturnal wakefulness after sleep onset in metabolic dysfunction–associated steatotic liver disease. Front Netw Physiol. 2024;4:1458665.
