This paper assesses the existing literature to explore the association between obstructive sleep apnea (OSA) and cirrhosis. While OSA's impact on metabolic dysfunction-associated steatotic liver disease (MASLD) is well-established, limited data exists for other causes of chronic liver disease. The review examines OSA's role in cirrhosis, emphasizing its potential influence on liver disease progression and laying the groundwork for future studies. Current data indicates a greater likelihood of liver disease in individuals with OSA, with continuous positive airway pressure (CPAP) treatment potentially slowing liver disease advancement. Undiagnosed OSA exacerbates liver disease progression, underscoring the urgency of identifying and managing sleep disturbances in patients with liver disease. Patients with a BMI over 30 and liver disease should be screened for sleep disturbances. Addressing sleep issues and OSA could enhance well-being and liver disease management in these patients.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a multisystemic disease with a multifactorial pathogenesis involving dietary, environmental, and genetic factors. Previous mouse models suggested that circadian misalignment may additionally influence its development as it influences metabolism in diverse organs including the liver. Further, data from sleep questionnaires proved sleep-wake disruption in patients with MASLD. We objectively assessed sleep-wake rhythms in patients with biopsy-proven MASLD (n = 35) and healthy controls (HC, n = 16) using actigraphy 24/7 for 4 weeks. With the aim to re-align sleep rhythms a single standardized sleep hygiene education session was performed after 2 weeks. Actigraphy data revealed that MASLD patients had more awakenings per night (MASLD vs. HC 8.5 vs. 5.5, p = 0.0036), longer wakefulness after sleep onset (MASLD vs. HC 45.4 min vs. 21.3 min, p = 0.0004), and decreased sleep efficiency (MASLD vs. HC 86.5% vs. 92.8%, p = 0.0008) compared with HC despite comparable sleep duration. Patients with MASLD self-reported shorter sleep duration (MASLD vs. HC 6 h vs. 6 h 45 min, p = 0.01) and prolonged sleep latency contributing to poorer sleep quality. Standardized sleep hygiene education did not produce significant changes in sleep parameters. Our findings indicate fragmented nocturnal sleep in patients with MASLD, characterized by increased wakefulness and reduced sleep efficiency, perceived subjectively as shortened sleep duration and delayed onset. A single sleep hygiene education session did not improve sleep parameters.

Obstructive sleep apnea (OSA), a common sleep-disordered breathing condition, is characterized by intermittent hypoxia (IH) and sleep fragmentation and has been implicated in the pathogenesis and severity of nonalcoholic fatty liver disease (NAFLD). Abnormal molecular changes mediated by IH, such as high expression of hypoxia-inducible factors, are reportedly involved in abnormal pathophysiological states, including insulin resistance, abnormal lipid metabolism, cell death, and inflammation, which mediate the development of NAFLD. However, the relationship between IH and NAFLD remains to be fully elucidated. In this review, we discuss the clinical correlation between OSA and NAFLD, focusing on the molecular mechanisms of IH in NAFLD progression. We meticulously summarize clinical studies evaluating the therapeutic efficacy of continuous positive airway pressure treatment for NAFLD in OSA. Additionally, we compile potential molecular biomarkers for the co-occurrence of OSA and NAFLD. Finally, we discuss the current research progress and challenges in the field of OSA and NAFLD and propose future directions and prospects.

Patients with obstructive sleep apnea (OSA) experience insulin resistance and its clinical consequences, including hypertriglyceridemia, reduced high density lipoprotein-associated cholesterol (HDL-c), visceral adiposity, hepatic steatosis, increased epicardial fat thickness, essential hypertension, glucose intolerance, increased risk for type 2 diabetes, chronic kidney disease, subclinical vascular damage, and increased risk for cardiovascular events. Obesity is a major contributor to OSA. The prevalence of OSA is almost universal among patients with severe obesity undergoing bariatric surgery. However, insulin resistance and its clinical complications occur in OSA patients irrespective of general obesity (body mass index). In OSA patients, apnea episodes during sleep induce oxyhemoglobin desaturation and tissue hypoxia. Insulin resistance is an adaptive response to tissue hypoxia and develops in conditions with limited tissue oxygen supply, including healthy subjects exposed to hypobaric hypoxia (high altitude) and OSA patients. Indicators of oxyhemoglobin desaturation have been robustly and independently linked to insulin resistance and its clinical manifestations in patients with OSA. Insulin resistance mediates the elevated rate of type 2 diabetes, chronic kidney disease, and cardiovascular disease unexplained with traditional cardiovascular risk factors present in OSA patients. Pathophysiological processes underlying hypoxia-induced insulin resistance involve hypoxia inducible factor-1 upregulation and peroxisome proliferator-activated receptor-gamma (PPAR- γ ) downregulation. In human adipose tissue, PPAR- γ activity promotes glucose transport into adipocytes, lipid droplet biogenesis, and whole-body insulin sensitivity. Silencing of PPAR- γ in the adipose tissue reduces glucose uptake and fat accumulation into adipocytes and promotes insulin resistance. In conclusion, tissue hypoxia drives insulin resistance and its clinical consequences in patients with OSA, regardless of body mass index.

Studies have shown that non-alcoholic fatty liver disease (NAFLD) may be associated with sleep disorders. In order to explore the explicit relationship between the two, we systematically reviewed the effects of sleep disorders, especially obstructive sleep apnea (OSA), on the incidence of NAFLD, and analyzed the possible mechanisms after adjusting for confounding factors. NAFLD is independently associated with sleep disorders. Different sleep disorders may be the cause of the onset and aggravation of NAFLD. An excessive or insufficient sleep duration, poor sleep quality, insomnia, sleep-wake disorders, and OSA may increase the incidence of NAFLD. Despite that some research suggests a unidirectional causal link between the two, specifically, the onset of NAFLD is identified as a result of changes in sleep characteristics, and the reverse relationship does not hold true. Nevertheless, there is still a lack of specific research elucidating the reasons behind the higher risk of developing sleep disorders in individuals with NAFLD. Further research is needed to establish a clear relationship between NAFLD and sleep disorders. This will lay the groundwork for earlier identification of potential patients, which is crucial for earlier monitoring, diagnosis, effective prevention, and treatment of NAFLD.

Epidemiological observations, experimental studies and clinical data show that obesity is associated with a higher risk of developing different types of cancer; however, proof of a cause-effect relationship that meets the causality criteria is still lacking. Several data suggest that the adipose organ could be the protagonist in this crosstalk. In particular, the adipose tissue (AT) alterations occurring in obesity parallel some tumour behaviours, such as their theoretically unlimited expandability, infiltration capacity, angiogenesis regulation, local and systemic inflammation and changes to the immunometabolism and secretome. Moreover, AT and cancer share similar morpho-functional units which regulate tissue expansion: the adiponiche and tumour-niche, respectively. Through direct and indirect interactions involving different cellular types and molecular mechanisms, the obesity-altered adiponiche contributes to cancer development, progression, metastasis and chemoresistance. Moreover, modifications to the gut microbiome and circadian rhythm disruption also play important roles. Clinical studies clearly demonstrate that weight loss is associated with a decreased risk of developing obesity-related cancers, matching the reverse-causality criteria and providing a causality correlation between the two variables. Here, we provide an overview of the methodological, epidemiological and pathophysiological aspects, with a special focus on clinical implications for cancer risk and prognosis and potential therapeutic interventions.

Obstructive sleep apnea (OSA) is associated with heart derangements detected at echocardiography as higher left ventricular mass index (LVMI), higher left ventricular end-diastolic diameter, lower left ventricular ejection fraction (LVEF), and impaired diastolic function. However, the currently used parameter to define OSA diagnosis and severity, the apnea/hypopnea index (AHI), poorly predicts cardiovascular damage, cardiovascular events, and mortality. Our study aimed to assess if other polygraphic indices of OSA presence and severity, in addition to AHI, might better predict echocardiographic cardiac remodeling.

We enrolled two cohorts of individuals referred for suspected OSA to the outpatient facilities of the IRCCS Istituto Auxologico Italiano, Milano, and of the Clinica Medica 3, Padova. All patients underwent home sleep apnea testing and echocardiography. Based on the AHI the cohort was divided into no-OSA (AHI<15 events/hour) and moderate-severe OSA (AHI≥15 events/hour). We recruited 162 patients and found that compared to patients with no-OSA, those with moderate-severe OSA showed higher LV remodeling [left ventricular end-diastolic volume (LVEDV) 48.4 ± 11.5 ml/m2 vs. 54.1 ± 14.0 ml/m2, respectively, p = 0.005] and lower LVEF (65.3 ± 5.8% vs. 61.6 ± 7.8%, respectively, p = 0.002), whereas we could not find any difference in LVMI and early and late ventricular filling velocity ratio (E/A). At multivariate linear regression analysis two polygraphic hypoxic burden-related markers were independent predictors of LVEDV and E/A, i.e., the percentage of time with O2 saturation below 90% (β = 0.222) and ODI (β = -0.422), respectively.

Our study shows that nocturnal hypoxia-related indexes were associated with left ventricular remodeling and diastolic dysfunction in OSA patients.

Chronic intermittent hypoxia (CIH) causes lung injury but the mechanism is unclear. Ferroptosis is a novel form of programmed cell death. In this research, we attempted to explore the role of ferroptosis in CIH-induced lung injury both in vitro and in vivo.

Sprague-Dawley rats were randomly separated into control group, CIH group and CIH + ferrostatin-1 group (CIH + Fer-1). Rats in the CIH group and CIH + Fer-1 group were exposed to intermittent hypoxia for 12 weeks. Human bronchial epithelial cell line (BEAS-2B) was cultivated for 24 h in either conventional culture medium or under CIH conditions. Fer-1 was applied to observe its treatment effects. Histological changes were evaluated by Hematoxylin-eosin (HE) staining and masson staining. The expression levels of Acyl-CoA synthetase long-chain family member 4 (ACSL4), glutathione peroxidase 4 (GPX4), interleukin-6 (IL-6) and tumour necrosis factor α (TNFα) were detected via qRT-PCR or Western blot. Cell counting kit-8 (CCK-8) was used to assess cell viability. The apoptotic rate and reactive oxygen species (ROS) was calculated by flow cytometry.

Histology showed that CIH treatment induced lung injury and pulmonary fibrosis in lung tissue. After Fer-1 treatment, the pathological changes caused by CIH alleviated. The mRNA and protein levels of GPX4 decreased significantly in lung tissues of CIH-treated rats and BEAS-2B, (p < 0.05). The mRNA and protein levels of ACSL4 increased significantly in lung tissues of CIH-treated rats and BEAS-2B, (p < 0.05). The mRNA levels of IL-6 and TNFα in BEAS-2B increased after CIH treatment, (p < 0.05). Cell viability decreased, apoptosis rate and ROS increased in CIH-treated BEAS-2B, (p < 0.05). Cotreatment with Fer-1 reversed CIH-induced apoptosis, cell viability, ROS accumulation, mRNA and protein levels of GPX4, ACSL4, IL-6 and TNFα both in vitro and in vivo (p < 0.05).

Ferroptosis occurred in CIH-induced lung injury, both in vitro and in vivo. The ferroptosis inhibitor Fer-1 alleviated cell injury and ferroptosis in CIH-treated BEAS-2B and lung tissues of rats.

Nonalcoholic fatty liver disease (NAFLD) is strongly associated with sleep apnea syndrome (SAS). Many NAFLD patients have SAS, and obstructive sleep apnea hypopnea syndrome is also considered to be an independent risk factor for NAFLD, as it contributes to the progression of NAFLD via oxidative stress, lipid peroxidation, inflammation, and insulin resistance. This review aims to provide some recommendations for the management of NAFLD patients with SAS, including diet, exercise, weight loss, and continuous positive airway pressure. This review also highlights the importance of effective strategies in NAFLD prevention and treatment.