Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), formerly known As Non-Alcoholic Fatty Liver Disease (NAFLD), is a highly prevalent chronic liver disease closely linked to obesity, metabolic syndrome, and insulin resistance. While metabolic dysfunction is a well-established driver of MASLD pathogenesis, emerging evidence highlights a significant association between MASLD and sleep disorders, including Obstructive Sleep Apnea (OSA), insomnia, and circadian misalignment. Sleep disturbances contribute to disease progression through multiple mechanisms, including chronic intermittent hypoxia, systemic inflammation, oxidative stress, insulin resistance, and dysregulated lipid and glucose metabolism, all of which promote hepatic steatosis and fibrosis. Given the growing recognition of these interactions, targeted interventions addressing sleep disturbances may represent a novel therapeutic approach in MASLD management. This review synthesizes the available data on the relationship between MASLD and sleep disorders, elucidating the underlying pathophysiological mechanisms, clinical implications, and emerging therapeutic strategies.

• Metabolic Dysfunction-Associated Steatotic Liver Disease
• Metabolic Dysfunction-Associated Steatohepatitis
• Sleep Disorders
• Obstructive Sleep Apnea
• Insomnia
• Liver Disease Progression

Stryelkina M, Nguyen M, and Vincent JL (2025) The Interplay between Sleep Disorders and MASLD: A Mini Review. J Sleep Med Disord 9(1): 1145.

MASLD: Metabolic Dysfunction-Associated Steatotic Liver Disease; NAFLD: Non-Alcoholic Fatty Liver Disease; MASH: Metabolic Dysfunction-Associated Steatohepatitis; HCC: Hepatocellular Carcinoma; OSA: Obstructive Sleep Apnea; CIH: Chronic Intermittent Hypoxia; HIF-1α: Hypoxia-Inducible Factor 1-Alpha; TNF-α: Tumor Necrosis Factor-Alpha; IL-6: Interleukin-6; PSQI: Pittsburgh Sleep Quality Index; ALAT: Alanine Aminotransferase; ASAT: Aspartate Aminotransferase; BMI: Body Mass Index; CPAP: Continuous Positive Airway Pressure

MASLD is among the most common chronic liver diseases worldwide, affecting an estimated 25-30% of the global population [1-3]. Its rising incidence is driven by the growing prevalence of metabolic syndrome, obesity, and insulin resistance, reflecting its role as the hepatic manifestation of metabolic syndrome [3-5]. MASLD encompasses a broad histopathological spectrum, ranging from simple hepatic steatosis to Metabolic Dysfunction- Associated Steatohepatitis (MASH), which can progress to fibrosis, cirrhosis, and Hepatocellular Carcinoma (HCC) [1,3,6]. While hepatic complications of MASLD are well characterized, accumulating evidence suggests a significant interplay between MASLD and extrahepatic conditions, including cardiovascular disease, chronic kidney disease, and, more recently, sleep disorders.

Sleep disturbances, including poor sleep quality, insomnia, irregular sleep duration, and Obstructive Sleep Apnea (OSA), are increasingly recognized as contributing factors in MASLD pathogenesis and progression. The underlying pathophysiological mechanisms linking sleep disorders and MASLD include systemic inflammation, oxidative stress, insulin resistance, dysregulated glucose and lipid metabolism, and gut microbiota alterations, all of which contribute to hepatic steatosis and fibrosis. This review examines the pathophysiological mechanisms linking sleep disturbances to MASLD progression and evaluates potential therapeutic strategies. Specifically, it explores the role of CPAP therapy in mitigating OSA- related metabolic dysfunction and liver injury.

Pathophysiology of OSA in MASLD

The association between OSA and MASLD is well established, with a growing body of evidence identifying OSA as a significant contributor to the pathogenesis and progression of MASLD. OSA is characterized by recurrent episodes of upper airway obstruction during sleep, resulting in Chronic Intermittent Hypoxia (CIH), oxidative stress, and systemic inflammation. Emerging research indicates that CIH in OSA induces insulin resistance and dyslipidemia, both of which play critical roles in MASLD development [7]. Furthermore, hypoxic conditions activate the Hypoxia-Inducible Factor 1-alpha (HIF-1α) pathway, promoting hepatic lipogenesis and oxidative stress, thereby exacerbating hepatic steatosis and fibrosis [7].

Systemic inflammation in OSA is characterized by elevated levels of pro-inflammatory cytokines, including Tumor Necrosis Factor-alpha (TNF-α) and Interleukin-6 (IL-6), which contribute to hepatocellular injury and fibrotic remodeling. Studies have demonstrated that patients with OSA exhibit significantly higher circulating levels of TNF-α and IL-6 compared to control populations, with these elevations correlating with disease severity [8- 11].

Clinical Evidence Linking OSA and MASLD

Clinical studies consistently demonstrate a strong association between the severity of OSA and the progression of MASLD. A systematic review and meta- analysis conducted by Musso, et al., reported that OSA is associated with an increased risk of MASLD, MASH, and liver fibrosis, with the severity of liver disease correlating with the severity of OSA [12]. Similarly, a systematic review and meta-analysis by Jin, et al., found that OSA severity is linked to elevated liver enzyme levels and histological features of MASLD, including steatosis, inflammation, and fibrosis [13]. Furthermore, Umbro, et al., observed a higher prevalence of MASLD among patients with OSA, even in the absence of obesity or metabolic syndrome, and reported a positive correlation between the severity of MASLD and OSA severity [14].

Observational studies further support the impact of OSA on the severity and progression of MASLD. Petta, et al., and Benotti, et al., demonstrated a strong association between OSA severity and the severity of MASLD [15,16]. Similarly, a large cross-sectional study by Sukahri, et al., identified a significant correlation between the degree of hepatic steatosis in MASLD and OSA severity [17]. Additionally, a large cohort study by Trzepizur, et al., reported that severe OSA is independently associated with increased liver stiffness, suggesting a higher risk of advanced liver disease [18].

Impact of Sleep Duration and Quality on MASLD

Growing evidence suggests that poor sleep quality and short sleep duration significantly contributes to the severity and progression of MASLD. Bernsmeier, et al., found that MASLD patients had shorter sleep duration (6.3 vs. 7.2 hours), and poorer sleep quality (PSQI: 8.2 vs. 4.7), than healthy controls, which correlated with elevated liver enzymes (ALAT, ASAT), and increased insulin resistance, indicating greater disease severity [19]. Similarly, Kim, et al., reported that short sleep duration (≤ 5 hours), was independently associated with an increased risk of MASLD, particularly in women, even after adjusting for BMI and other confounders [20]. Furthermore, Marin- Alejandre, et al., found that sleep disturbances, including both reduced sleep duration and poor sleep quality, were prevalent among obese individuals with MASLD and were significantly correlated with worsened hepatic outcomes, such as increased liver stiffness and elevated transaminase levels [21]. Interestingly, a recently published large cross- sectional study found that intermediate to late sleep timing with normal sleep duration increased MASLD risk, especially in men and those with cardiometabolic conditions [22].

Insomnia and MASLD Progression

Insomnia, a prevalent sleep disorder characterized by difficulty initiating or maintaining sleep, has been implicated in the pathogenesis and progression of MASLD through multiple pathophysiological mechanisms. Insomnia exacerbates metabolic dysfunction, including insulin resistance and systemic inflammation, both of which are central to MASLD development. Chronic sleep deprivation and poor sleep quality contribute to increased levels of pro-inflammatory cytokines and oxidative stress, promoting hepatic inflammation and fibrosis [23,24]. Several studies have established a significant association between insomnia and hepatic dysfunction. A Mendelian randomization study identified a causal relationship between insomnia and elevated alanine transaminase levels, as well as increased hepatic fat content, underscoring its direct impact on liver health [24]. Furthermore, a cross- sectional observational study demonstrated that poor sleep quality and reduced sleep duration correlate with increased liver stiffness and elevated liver enzyme levels, suggesting more advanced hepatic injury [25]. Disrupted sleep patterns also contribute to circadian misalignment, which impairs lipid metabolism and glucose homeostasis, exacerbating hepatic steatosis [26]. Circadian disruption enhances hepatic stellate cell activation, driving fibrosis and facilitating MASLD progression to MASH [27-31].

While CPAP therapy has been extensively studied for its potential benefits in OSA-related MASLD, other sleep-related factors, such as chronotype and circadian rhythm disruptions, may also play a significant role in disease progression. Chronotype, an individual’s natural preference for sleep and activity timing, has been identified as a key factor influencing MASLD severity (Table 1).

Table 1: Summary of Key Studies and Principal Findings Referenced in This Review.

Vetrani, et al., found that evening chronotypes, or people who tend to eat later and have delayed sleep-wake cycles, are associated with more severe MASLD, independent of age, gender, and BMI [32]. Moreover, a recent study reported that evening and intermediate chronotypes have a higher risk of significant and advanced liver fibrosis [33]. Given these associations, chronotherapy-an approach that aligns circadian rhythms with metabolic cycles-may offer a novel strategy for MASLD management by optimizing meal timing, sleep patterns, and lifestyle interventions to improve metabolic homeostasis and liver health [34].

The existing literature has several limitations. Many studies rely on subjective sleep assessments, such as self- reports and questionnaires, which are prone to recall bias and may not accurately reflect sleep patterns. Additionally, confounding factors such as obesity, metabolic syndrome, and physical activity independently affect both sleep and liver health, complicating interpretations. In conclusion, sleep disorders, including OSA, insomnia, and circadian disruptions, contribute to MASLD progression through shared mechanisms such as inflammation, oxidative stress, insulin resistance, and gut dysbiosis. Addressing sleep dysfunction in MASLD patients through sleep disorder screening, CPAP therapy, sleep hygiene interventions, and chronotherapy may serve as a novel adjunctive approach in managing this growing public health burden. As research continues to uncover the complex relationship between sleep and liver disease, integrating sleep medicine into hepatology practice may improve overall metabolic and hepatic health in MASLD patients.

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