阻塞性睡眠呼吸暂停中的慢性间歇性低氧与MASLD：对机制与因果证据的批判性评价

文献信息

中文摘要

阻塞性睡眠呼吸暂停（OSA）与代谢功能障碍相关脂肪性肝病（MASLD）常共存，并通过共同的代谢心血管基础相互关联。本叙述性综述批判性评价了旨在将慢性间歇性低氧（CIH）和睡眠片段化与肝脂肪变性、脂肪性肝炎和纤维化联系起来的流行病学、实验和干预证据。我们总结了候选机制，包括线粒体氧化应激、缺氧诱导因子1-α信号、交感驱动的脂解以及Kupffer细胞和星状细胞活化，然后审视支持这些机制的证据局限性：低氧诱导的摄食减少及啮齿动物模型中配对喂养对照的缺乏、对低氧生理反应的物种差异、发表偏倚、年龄和全身性炎症导致的共同原因混杂，以及解剖驱动型OSA的瘦患者中进展性肝病罕见。我们进一步综述了无创诊断工具、多导睡眠图低氧血症指标、瞬时弹性成像、METS-IR、FIB-4以及新兴生物标志物（如omentin-1和卵泡抑素样1），这些工具可实现睡眠与肝病门诊之间的双向筛查。最后，我们讨论了治疗策略，包括持续气道正压通气、结构化减重和基于肠促胰素的药物治疗（GLP-1及GIP/GLP-1双受体激动剂），重点介绍了替尔泊肽治疗OSA和司美格鲁肽治疗代谢功能障碍相关脂肪性肝炎的近期3期证据。当前证据支持CIH是既存代谢功能障碍患者肝损伤的情境依赖性放大因素，而非MASH的既定独立病因。这一解释仍支持整合筛查和治疗路径，同时明确了直接检验因果关系所需的研究设计。

英文摘要

Obstructive sleep apnea (OSA) and metabolic dysfunction-associated steatotic liver disease (MASLD) frequently coexist and share a common cardiometabolic substrate through a shared cardiometabolic substrate. This narrative review critically appraises the epidemiological, experimental, and interventional evidence proposed to link chronic intermittent hypoxia (CIH) and sleep fragmentation to hepatic steatosis, steatohepatitis, and fibrosis. We summarize the candidate mechanisms, including mitochondrial oxidative stress, hypoxia-inducible factor 1-alpha signaling, sympathetically driven lipolysis, and Kupffer and stellate cell activation and then examine the limits of the evidence supporting them: hypoxia-induced hypophagia and the scarcity of pair-fed controls in rodent models, species differences in the physiological response to hypoxia, publication bias, common-cause confounding by age and systemic inflammation, and the rarity of progressive liver disease in lean patients with anatomically driven OSA. We further review non-invasive diagnostic tools, polysomnographic hypoxemia indices, transient elastography, METS-IR, FIB-4, and emerging biomarkers, such as omentin-1 and follistatin-like 1, that enable bidirectional screening between sleep and hepatology clinics. Finally, we discuss therapeutic strategies, including continuous positive airway pressure, structured weight loss, and incretin-based pharmacotherapy (GLP-1 and dual GIP/GLP-1 receptor agonists), highlighting recent phase 3 evidence for tirzepatide in OSA and semaglutide in metabolic dysfunction-associated steatohepatitis. Current evidence supports CIH as a context-dependent amplifier of liver injury in patients with pre-existing metabolic dysfunction rather than as an established independent cause of MASH. This interpretation still justifies integrated screening and treatment pathways, while identifying the study designs needed to test causality directly.